WO2015148958A1

WO2015148958A1 - Devices, systems, and methods for particle separation

Info

Publication number: WO2015148958A1
Application number: PCT/US2015/023053
Authority: WO
Inventors: Brian Bothner; Joshua HEINEMANN
Original assignee: Montana State University
Priority date: 2014-03-27
Filing date: 2015-03-27
Publication date: 2015-10-01

Abstract

Devices, systems, and methods for particle separation are disclosed. In some embodiments, a fluidic device is used to separate particles from a fluid. In some embodiments, a pump and valve system are used to pull a sample fluid form a source and provide the sample to the device to separate particles from the fluid. In some embodiments, a detector is included to detect particles separated from a fluid using a device and system disclosed herein. In some embodiments, the present invention teaches methods for separating a particle from a fluid and detecting the separated particle.

Description

DEVICES, SYSTEMS, AND METHODS FOR PARTICLE SEPARATION Cross-Reference To Related Applications

This application claims priority to U.S. Provisional Application No. 61/971,254, filed March 27, 2014, entitled "Metabolite extraction chip for the automated, real-time digitization of metabolic patterns from living systems," the entire disclosure of which is hereby incorporated by reference in its entirety. Statement Regarding Federally Sponsored Research Or Development This invention was made with government support under MCB 1022481, awarded by the National Science Foundation, The United States Government has certain rights in the invention. Background

The separation of particles from a fluid has applications in fluid purification and the capture of separated particies, e.g. analysis, e.g. diagnostics. There is a need for systems that efficiently separate particles f om complex mixtures. Particies can be removed from a fluid via filtration or adsorption; however, these separation processes are not compatible with rapid analysis of the separated particles. Liquid chromatography mass spectrometry (LC/MS) is the standard in separating and analyzing particles in a fluid. Particles in a fluid are separated in tenns of affinity for a stationary phase, and a mass spectrometer detects the separated particies for mass analysis. Anaiysis of the detected particles by mass spectrometry can provide information on, for example, particle identity and the relative abundance of particles in complex fluid mixtures. However, sample optimization is required to ensure that sufficient sample is detected while avoiding fouling of the detector, which impedes abundance measurements at discrete time- points.

Examples of additional technologies that have been used to separate particles include: membrane microfiUration, pinched flow fractionation, deterministic lateral displacement, hydrodynamic chromatography, hydrophoresis, di electrophoresis, immunomagnetic-based isolution, magnetic separation (Pamme, N, et. al., Anal. Chem. 2004; 76:7250-7256), optical fractionation (MacDonald, MP, et. al., Nature Dec 2003:426 (6965);421-4), asymmetric bifurcation of laminar flow around obstacles (Huang LR, et.aL Science 2004 May 14; 3G4(5673):987-90), a massively parallel micro-sieving device (Mohamed H, eta., IEEE Trans ^'Nanobioscience, 2004 Dec I 3(4):251-6), biomimetic autoseparation (Skevkopiyass SS, et a!,, Anal Chem. 2005 Feb 1; 77(3): 937-7), passively driven microfluidic separation (Clio BS, et. al., Anal, Chem. 2003 Apr 1 ;75(7): 1671 -5), microchip capillary electrophoresis (Gareia-Perez, 1, et. al, 2008 Sep 19:1204(2): 130-9), microchip liquid chromatography (Lin, YQ, et, al, Anal. Chem. 2008:80(21);8045-54), hydrogel bacterial microchip (Fesenko, DO, et. al., Biosens, Bioelectron. 2009:20; 1860-5), droplet microfluidics, and microscale laminar vortices. These systems are complex, require laborious sample preparation, and/or are not otherwise compatible for rapid separation and/or detection. Furthermore, these technologies are not suited for separating desired particles from a source fluid into a solvent for detection without initial sample preparation.

Of these technologies, microfluidic systems can rapidly separate particles in a fluid based on physical properties and/or chemical properties of a particles (e.g. size, optical signal, binding affinity, combinations thereof and the like). Geometrically constrained channels and small fluid volumes impart unique properties on fluids that enables for precise control of flowing fluids, including particles suspended therein. For example, spiral rmcrochannels have been used to focus particles suspended in a fluid to finite positions in the channel based on particle diameter. However, existing microfluidic technologies are limited to sorting discrete particles in simple mixtures within a single fluid based on diameter, and optically verifying the sorting of particles . To analyze particles in complex fluids (e.g., biological fluids, such as blood, urine, and/or the like), analytes (e.g., metabolites) need to be separated from undesired particles (e.g., cell lysates) and transferred to a solvent compatible with a detector (e.g., mass spectrometer).

Thus, there exists a need to rapidly separate and detect particles from complex fluids. Summary

In some embodiments, devices, systems, and methods for the separation of particles in fluids are disclosed herein. In some embodiments, a device includes a first inlet configured to receive a first fluid and a second inlet configured to receive a second fluid, the second fluid having particles of a substance suspended therein. In some embodiments, the device includes a channel with one or more loops formed as a spiral. The spiral includes a first end and a second end, the first end being closer to an outer point of the spiral relative to the second end. The channel is fluidly coupled to the first inlet and to the second inlet at the first end. The channel is configured to receive the first fluid from the first inlet and the second fluid from the second inlet. The channel is further configured to draw at least a portion of the suspended particles from the second fluid into the first fluid based a characteristic of the suspended particles. The device also includes a first outlet fluidly coupled to the second end of the channel, the first outlet configured to receive the first fluid including the portion of the drawn particles. The device also includes a second outlet fluidly coupled to the second end of the channel, the second outlet configured to receive the second fluid. In some embodiments, a kit for separating particles includes the device as disclosed herein. In some embodiments, a system for separating and detecting particles is disclosed herein. In some embodiments, the system includes a device. The device includes a first inlet configured to receive a first fluid and a second inlet configured to receive a second fluid, which second fluid has particles of a substance suspended therein. The device also includes a channel including one or more loops formed as a spiral, the channel includes a first end and a second end, the first end being closer to an outer point of the spiral relative to the second end. The channel is fluidly coupled to the first inlet and to the second inlet at the first end. The channel is configured to receive the first fluid from the first inlet and the second fluid from the second inlet. The channel is further configured to draw at least a portion of the suspended particles from the second fluid into the first fluid based on a characteristic of the suspended particles. The device also includes a first outlet fluidly coupled to the second end of the channel, the first outlet configured to receive the first fluid including the portion of the drawn particles, and a second outlet fluidly coupled to the second end of the channel, the second outlet configured to receive the second fluid. The system also includes a pump fluidly coupled to a first source of the first fluid and a second source of the second fluid, and the pump is further fluidly coupled to the first inlet of the device and the second inlet of the device. The pump is configured to pull the first fluid from the first source and the second fluid from the second source. The pump is further configured to provide the first fluid to the first inlet and the second fluid to the second inlet of the device. The system also includes a valve fluidly coupled to the pump, the valve is configured to, in a first setting, permit fluid flow from the first source of the first fluid and from the second source of the second fluid to the pump. The valve is further configured to, in a second setting, direct the pump to permit fluid flow from the pump to the first inlet and to the second inlet of the device, the first fluid provided to the first inlet and the second fluid provided to the second inlet. The system also includes a detector fhrklly coupled to the first outlet of the device, the detector configured to detect particies drawn into the first fluid from the second fluid. Particles drawn into the first fluid exit the device at the first outlet. In some embodiments, a kit for separating particles includes the system as disclosed herein, In some embodiments, a method to separate particles is disclosed herein. In some embodiments, the method includes receiving a first fluid and a second fluid in a channel of a device in laminar flow such that turbulent mixing of the first fluid and the second fluid does not occur, the second fluid containing particles of a substance suspended therein. The method also includes drawing at least a portion of particles suspended in the second fluid from the second fluid into the first fluid based on a characteristic of the suspended particles. The method also includes separating the first fluid from the second fluid, the first fluid including the portion of drawn particles. In some embodiments, a kit for separating particles includes a separation device, and further includes one or more of the following: a pump, one or move valves, a detector, a controller, and tubing. Brief Description of the Drawings The following drawings are provided to aid in the understanding of the subject matter disclosed herein. The embodiments set forth in the drawings are illustrative nature, and not intended to limit the subject matter defined by the claims. The following detailed description of the illustrative embodiments can be understood when read in conjunction with the following drawings: FIG. 1 is an il lustrative design of a separation device, according to an embodiment, FIG. 2 is an illustrative design of a separation structure, according to an embodiment. FIG. 3 is an illustrative design of a spiral separation structure, according to an embodiment. FIG. 4A is an illustrative diagram of a spiral separation structure, according to an embodiment. FIG. 4B illustrates cross-section views of the microfluidic channels of the spiral separation structure of FIG. 4A at the beginning (sample input), middle section, and final section (sample output), accordmg to an embodiment. FIG. 5A is an illustrative diagram of a 5 loop spiral separation stmcture, accordmg to an embodiment. FIG. 5B is an illustrative diagram of a 3 loop spiral separation structure, according to an embodiment. FIG. 6 is an illustrative diagram of a 5 -loop logarithmic spiral separation structure having a first inlet, a second inlet, a first outlet, and a second outlet, according to an embodiment. FIG. 7 A. schematically illustrates a pump and a valve system in a first setting for drawing fluids, according to an embodiment. FIG. 7B schematically illustrates a pump and a valve system in a second setting for providing fluids to a device, according to an embodiment. FIG. 8 depicts an illustrative diagram of a mixing structure, accordmg to an embodiment. FIGS. 9A-9C are schematic illustrations of a particle separation structure with cross- sectional views of particle separation shown as a function of channel location, according to an embodiment. FIG. 9A shows a manufactured prototype of a particle separation structure fabricated using PDM8, according to an embodiment. FIG. 9B shows particles of a substances suspended in a second fluid entering a particle separation structure at a second inlet, according to an embodiments. FIG. 9C shows a portion of particles separated from a second fluid into a first fluid exiting a particle separation structure at a first outlet, according to an embodiment. FIGS. 10A and 10B schematically depict illustrative diagrams of systems to separate and detect particles, accordmg to an embodiment. FIG. 10A schematically illustrates a system to separate particles from a second fluid into a first fluid and to detect separated particles, according to an embodiment. FIG. 10B schematically illustrates a system to mix fluids, to separate particles using spiral channels, to detect particles, according to an embodiment. FIG. 11A photographically illustrates fluid coupling of a syringe to a modified needle, according to an embodiment. FIG. 1 IB photographically illustrates fluid coupling of a syringe to a modified needle matched to an inlet of a device, according to an embodiment. FIG. 12 illustrates a method for separating particles, according to an embodiment. FIG. 13A graphically depicts a total ion count (TIC) of particles separated using a spiral separation structure, according to an embodiment. FIG. 13B graphically illustrates an overlay of the TIC for particles separated at different sample injection times points, according to an embodiments. FIG. 14A graphically illustrates the extracted ion chromatogram (EIC) of an oxidized glutathione (GSSG) standard overlaid with an EIC of GSSG separated from a source fluid using a spiral separation structure, according to an embodiment. FIG. 14B graphically illustrates the resolved isotopic peaks of the GSSG separated from the source fluid, according to an embodiment. FIG. 15A graphically illustrates the abundance changes of 77 metabolites detected in an E. coli cell culture, according to an embodiment. FIG. 15B graphical ly illustrates abundance changes of four metabolites separated from an E, coli culture, which exhibit smooth transitions over 6 hr., according to an embodiment. FIG. 15C graphically illustrates abundance change of four metabolites separated from an E. coli cuiture, which exhibit oscillatory changes over 6 hr., according to an embodiment. FIG. 16 graphically illustrates principal component analysis (PCA) of 77 metabolites detected in an E. coli cell growth culture at 15 sequential time points, according to an embodiment. FIG. 17 graphically illustrates real-time analysis of particles separated from E. coli cell cultures during 8.5 hr. growth monitoring, according to an embodiment. FIG. 18 graphically illustrates changes in abundance of five small molecules in an E. coli cell culture before and after oxidative stress, according to an embodiment. FIG. 19A graphically illustrates the EIC of 40 small molecules separated from a urine sample at 7 sequential time points, according to an embodiment. FIG. 19B graphically illustrates the EIC of creatinine separated from a urine sample at 7 sequential time points, according to an embodiment. FIG. 19C graphically illustrates the EIC of urea separated from a urine sample at 7 sequential time points, according to an embodiment. FIG. 20A graphically illustrates the EIC of 4 small molecules and 1 protein separated from a urine sample at 5 sequential time points, according to an embodiment. FIG. 20B graphically illustrates the EIC of 4 small molecules detected in a urine sample at 5 sequential time points, according to an embodiment. FIG. 20C graphically illustrates the EIC of Hemoglobin detected in a urine sample at 5 sequential time points, according to an embodiment. Detailed Description As used herein, the term "biological fluid," "biofluid" and variations thereof, refers to any fluid containing particles of biological origin, particles derived from a biological system, or synthetically generated molecules that are associated with biological systems. The term "biological fluid," and variations thereof, further includes any fluid in which particles are solubilized. Non-limiting examples of particles of biological origin and particles derived from a biological system include cells, cellular components, extracellular molecules, molecules found in or derived from a living system, synthetically generated molecules (e.g. synthetic proteins, synthetic polypeptides, synthetic nucleotides, drugs, and/or the like), the like, and/or combinations thereof. As used herein, the term "biomolecule," and variations thereof, refer to any particle derived from or found in a biological system, whether naturally occurring or synthetically generated, and can include organic, inorganic, hybrid, and synthetically generated molecules. As used herein, the term "metabolomics," and variations thereof, refers to the study of metabolite expression, either at a discrete time point and/or over a range of time points. For purposes of this specification, metabolomics includes but is not limited to the following: (i) metabonornics, which looks at the changes in the concentrations of a large number of metabolic markers over time; (ii) metabolic fmgerprintirig, which measures a global profile of metabolites to identify specific profiles based on pattern recognition; (iii) metabolic profiling, which measures a specific subset of compounds such as, but not limited to, amino acids, carbohydrates, and lipids; and (iv) targeted metabolic profiling, which tracks one or two discrete analytes over time, As used herein, the term "non-conductive, polymeric material," and variations thereof, refers to a polymeric material that cannot and/or does conduct electricity. The polymeric material can be composed of organic polymers, inorganic polymers, hybrid organic and inorganic polymers, the like, and/or combinations thereof. As used herein, the "particle," and variations thereof, refers to any entity deemed to have at least one characteristic on the basis of which it can be sorted such as physical properties (e.g, diameter, size, mass, solubility, etc.) and/or chemical properties (e.g. reactivity, etc.). Accordingly, the term particle includes, but is not limited to, organic particles, inorganic particles, biomolecules, hybrid particles having organic, inorganic, and/or biomolecule components, synthetic particles, and/or the like, and/or combinations thereof. "Substantially" and "about" may be used herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. These terms are also used herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. Some embodiments disclosed herein are operable for the separation of particles from mixtures, where particles with particular characteristics need to be isolated, e.g. for analysis. Embodiments disclosed herein are operable to perform this function while reducing size, cost, time, complexity of manufacture, and/or operation relative to prior art systems. FIG. 1 illustrates an embodiment of the modular nature of a particle separator, according to some embodiments. With particular reference to metabolomics, embodiments disclosed herein can serve the growing needs for fast extraction and analysis of cellular metabolites.

Additionally, embodiments disclosed herein provide complete systems for particle processing, and can encompass particle separation (e.g., via a fluidie device, described later), fluid supply (e.g, via a pump and valve system, described later), sample mixing (e.g., via a sample mixing structure, described later), and detection (e.g., via mass spectrometry, described later), some or all of which can he incorporated on a microfluidic scale. Embodiments described herein can further provide for optimization of particle separation based on the source of a fluid (e.g., blood, urine, or cell culture, as described herein) and/or the particles to be separated (e.g., metabolites). Embodiments described herein can further provide integrated systems for coupling to a living system (e.g., the human body). Embodiments disclosed herein can perform particle processing continuously and in real-time.

Furthermore, embodiments described herein provide improved methods to separate and interrogate particles. Embodiments described herein further provide improved systems and methods for metabolite separation (e.g., from cells, biofluids, and the like). Embodiments described herein can further separate metabolites from sources in real-time for fast analysis. Embodiments described herein can greatly reduce sample preparation and prevent detector fouling from molecular bui ldup.

As a non-limiting example, a device (e.g., spiral separation structure) can receive a sample (e.g., blood, urine, lysate contained lysed cells, and/or other particle-containing fluid) and separate a portion of particles suspended the sample. In some embodiments, prior to introduction to the device (e.g., a spiral particle separation structure), a mixing structure can mix a sample (e.g., cell culture) with a solution (e.g., cell lysis solution), and a fluid supply system (e.g., a pump and valve system) can provide the mixed sample as input to the device (e.g., a spiral particle separation structure). In some embodiments, a detector (e.g., a mass spectrometer) can detect particles.

Devices, systems, and methods for separating and detecting particles in fluids are described herein. In some embodiments, a particle is separated from a second fluid into a first fluid based on a c aracteristic of the particle. In some embodiments, a pump and valve system provide the first fluid and the second fluid. In some embodiments, a detector detects separated particles. Accordingly, aspects of this disclosure enable interrogation of at least a portion of particles in a fluid. Aspects of this disclosure are further operable to use information from the detection of separated particles for further analysis, such as for characterization, for measuring abundance profiles, metabolomics and/or the like. For example, metabolites can be separated from cells using a device described herein to reveal information about the cell and/or host. As cells carryout processes, metabolites are produced, which reveal information about the activity of the cell and of the host organism. In response to disease or stress, intracellular processes demonstrate specific temporal patterns of variation in metabolite abundance. (Schmidt, MD, et. al,, Physical Biology, 10 Aug 201 1 :8(5);055()1 1 ). Phenotype-specific patterns can emerge from the quantification of thousands of molecular features. (Tautenhahn, R, et. al.. Anal. Chem. 25 Apr 2012:84(11);5035-5039). Accordingly, metabolomics profiles can provide fingerprints of pathological and physiological conditions. Interpretation of metabolomic profiles using pattern recognition algorithms can create feature-based profiles that reveal cyclic patterns and forecastable metabolite trajectories. The ability to relate metabolomics profiles to intracellular processes is valuable in the detection and diagnosis of pathological and physiological conditions. Metabolomics profiles can be used to predicatively interpret the relationship between metabolite abundance patterns and phenotype. Metabolomics profiles provide phenotype information that can be used to detect and/or identify a biomarker, to biologically characterize the condition of an organism, to diagnosis a disease or condition, to monitor a biological system, and/or to develop an effective, personalized therapeutic regimen. Real-time digitization of changes in intracellular metabolic activities is, therefore, paramount to harnessing the therapeutic value of metabolomics.

In addition to real-time extraction and detection of metabolites from living systems to generate forecastable metabolomics profiles, which can be used for in vivo biomarker detection and point-of-care disease diagnosis, monitoring of biological fluids is also achievable. Non- limiting examples of applications for biological monitoring includes the detection of chemical and biological weapons in fluids, detection of narcotics in urine, microbial growth monitoring, which can be used to optimize, for example, antibody production for pharmaceutical applications, and bioengineering, such as monitoring biofuel production from a microbial host. Liquid chromatography-mass spectrometry can be used for the quantitation of molecular abundance, and is currently the standard for metabolomics due to high resolution and the ability to detect numerous molecules in a sample. Advances in modem mass spectrometry, along with the advent of modular detectors (e.g. microiluidic detectors, biosensors, monolithic MEMS Quadropole and the like), provide platforms for point-of-care applications, e.g. diagnostics. However, several obstacles render current technologies impractical for real-time monitoring due to their complexity', size, and high cost (e.g., lack of technologies for fast, continuous extraction of metabolites from biological fluids). Provided here, in some embodiments, is a microiluidic technology that allows for separation and detection of particles in fluids based a characteristic of the particles, such as mass. The particle separation capabilities of microfluidic devices and the timescale of parallelized LOC valving allows for microfluidic-based lab-on-chip technologies to be integrated with a mass spectrometer. ( elin, J., Quake, SR., Annu. Rev. Biophys. Biomol. Struct. I Feb 2007: 36;213-231).

In some embodiments, a microfluidic particle separation device is described herein that can separate particles in fluids based on a physical characteristic of the particles. In some embodiments, a microfluidic particle separation and detection system is described herein that can separate particles, e.g. metabolites, from sources, e.g. cells, biofluids, and/or the like. In some embodiments, a microfluidic particle separation and detection system can include (i) a pump and valve system, (ii) a mixing structure, (iii) a spiral separation structure, and (iv) a detector. In some embodiments, an armband can be mated to a device described herein to integrate the particle separation system with an organism. In some embodiments, a detector includes a monolithic MEMS Quadropole for modular and/or point-of-care diagnostic applications (Syms, R. U.S. Pat. No. 7,208,729. 29 Jul . 2003).

In some embodiments, a separation system described herein can be a cost-effective, rapid, reliable technology and methodology to (1) separate, (2) interrogate (e.g. identify), and (3) measure (e.g. abundance) metabolites from cells, whole blood, urine, and the like. Systems described herein have advantages over conventional metabolomics systems that are more expense, labor intensive, complicated to use, and very large. In some embodiments, the system disclosed herein can separate and detect particles with a separation efficiency of about 1% or more, about 10% or more, about 15% or more, about 20% or more, about 23% or more, about 26% or more, or about 30% or more, or about 40% or more, or from about 10% to about 100%, from about 10% to about 90%, from about 10% to about 80%, from about 10% to about 70%, or from about 10% to about 60%, from about 10% to about 50%, from about 10% to about 40%, from about 10% to about 30%, from about 10% to about 20%, or from about 25% to about 50% . In some embodiments, a system can separate and detect metabolites from cells, biofluids, and the like, at sample input intervals of about 6 minutes, about 5 minutes, about 3 minutes, or about 3 to about 5 minutes, including al l values and sub ranges in between. In some embodiments, the system disclosed herein increases the amount of information recovered from metabolomics experiments through the novel ability to detect oscillating metabolic transient states that change in real-time, either in response to stimuli, as a natural process, or the like. Separation Device

In some embodiments, a device is provided that can sort, separate, and/or collect particles based on a characteristic of the particles. In some embodiments, particles can be separated based on physical or chemical properties. For example, a particle can be separated on mass, size (e.g. diameter), solubility, reactivity with a biosensor, and/or the like, and/or combinations thereof. FIG. 2 illustrates an embodiment of a device 200 to separate particles into a first fluid 202 from a second fluid 203 containing particles of substance, the system including a separation structure 201. In some embodiments, a particle-containing fluid 203 is flowed through a separation structure. In some embodiments, a portion of particle less than a first mass is separated from the fluid 203 into the first fluid 202. In some embodiments, the particles of a substance can be of a mixed population of masses. Particle separation, in some embodiments, can refer to sorting, separating, and/or collecting metabolites based on mass from a fluid that can contain a population of metabolites of different masses. In some embodiments, the fluid containing metabolites can also include cell lysates, e.g. lysed cellular membrane.

In some embodiments, the separation device of FIG. 2 can include fluidic channels (not shown). In some embodiments, the separation device 200 can be embedded on, attached to, or embodied on a chip (e.g., a lab-on-a-chip, or the like). In some embodiments, the device operates in a temperature controlled environment, is encased in a temperature controlled structure, fabricated from a thermal resistant material, and/or is otherwise substantially resistant to temperature fluctuations. Particle Separation Structure In some embodiments, the separation device 200 includes a particle separation structure 201. In some embodiments, the particle separation structure 201 is a hydrodynamic micro fluidic structure including a spiral channel structure herein termed a spiral separation structure for use in separating particles, FIG. 3 illustrates an embodiment of a spiral separation structure 300, including at least one inlet 301, a spiral channel 302, a first outlet 303, and a second outlet 304. In some embodiments, the spiral separation structure 300 can be embedded on a chip (e.g. a lab- on-a-chip, or the like.). In some embodiments, the spiral separation structure 300 can be used to separate particles based on characteristics such as, for example, size (e.g. diameter), shape, mass, density, and/or the like. In some embodiments, the spiral separation structure 300 can separate particles less than a first mass from a fluid containing particles of a substance suspended therein, where the particles of the substance can be of a mixed population of masses. In some embodiments, the spiral structure 300 can separate metabolites less than a first mass from a solution of other particles (e.g. metabolites greater than the first mass, proteins, cell lysates, and/or the like). The spiral separation structure 300 employs spiral inertia! forces to achieve separation of particles. Inertia! lift forces and viscous drag forces acting on particles of various sizes suspended in a fluid flowing through the spiral channel 302 can achieve differential migration, and hence separation, of particles. Dominant spiral inertial forces of lift forces and Dean forces, resulting from the spiral fluidic microchar el geometry, can cause larger particles to occupy a single equilibrium position near the inner wail of the spiral channel . Small particles, under the influence of Dean drag force, migrate to the outer wall of the spiral channel. Accordingly, these spiral inertial forces can create distinct particle streams that can be collected in separate outlets 303 and 304. In some embodiments, due to large lift forces generated by high aspect ratio channels, particle separation can be achieved in short distances of spiral channels. FIG. 4A illustrates a spiral separation structure 400 that includes a first inlet 401 , a second inlet 402, a spiral fluidic channel 403 arranged in a plurality of loops, a first outlet 404, and a second outlet 405. Some or al l features of the separation stnicture 400 (e.g., channel 403, inlets 401 and 402, outlets 404 and 405, and the like) can be fabricated from a suitable micro- fabrication material. In some embodiments, a suitable micro-fabrication material is a non- conductive polymeric material. Non-limiting examples of suitable micro-fabrication materials include, but are not limited to, a poly-dimethylsiioxane (PDMS) material, a polymethylmethacrolate (PMMA) material, a polycarbonate (PC) material, a cyclic olefin copolymer (COC) material, the like, and/or combinations thereof. In some embodiments, micro- fabrication can be achieved using thermoplastic materials. Non-limiting examples of suitable thermoplastic material for micro-fabrication include a nylon material, an acrylic material, a polybenzimidazole material, a polyethylene material, a polypropylene material, a polystyrene material, a polyvinyl chloride material, a teflon material, the like, and/or combinations thereof. In some embodiments, the spiral separation structure 400 can be fabricated with thermoplastic materials using 3-D printing. In some embodiments, the first inlet 401 can be configured to receive a solvent and the second inlet 402 can be configured to receive a particle-laden solution that contains particles of substance of various masses. In some embodiments, at least one inlet (e.g., the inlet 401 or the inlet 402) can be connected to ports or to other coupling devices (e.g. configured to mate with a syringe, a pump and valve system, etc.) to allow a solution to enter a spiral particle separation structure. In some embodiments, at least one inlet can be provided. In some embodiments, more than two inlets can be provided. In some embodiments, the first inlet 401 and the second inlet 402 can be fiuidly coupled to the spiral fluidic channel 403 that is arranged in one or more loops. In some embodiments, a fluidic channel 403 can be of a substantially quadrilateral (e.g. rectangular, parallelogram, rhomboid, trapezoid, square, kite, and/or the like) cross section having two first walls (not shown) and two second walls (not shown). In some embodiments, the first walls are a top wall and a bottom wall defining a width of the fluidic channel 403, and (in some embodiments) the second walls define a height of the fluidic channel 403. In some embodiments, the fluidic channel 403 is substantially circular or oval in cross section. In some embodiments, the fluidic channel 403 having a substantially circular or oval cross section is defined, in part, by an internal diameter and/or radius, in some embodiments, the fluidic channel 403 can include a portion that is substantially quadrilateral in cross section and a portion that is substantially circular or oval in cross section. In some embodiments, two or more outlets can be provided. In some embodiments, as illustrated in FIG. 4A, a spiral fluidic channel 403 can include the first outlet 404 and the second outlet 405. In some embodiments, the first outlet 404 and the second outlet 405 can be located at opposite ends of the spiral fluidic channel 403 relative to the first inlet 401 and the second inlet 402. In some embodiments, the first outlet 404 and the second outlet 405 can be located at the second end of the fluidic spiral channel 403. In some embodiments, the first outlet 404 and the second outlet 405 can be fiuidly coupled to the second end of the spiral channel 403. In some embodiments, the first outlet 404 can be configured to receive a first fluid, the first fluid can include a portion of particles suspended therein. In some embodiments, the second outlet 405 can be configured to receive the second fluid, and the second fluid can contain a portion of particles not drawn into the first fluid. In some embodiments, particles are collected, detected, counted, or otherwise analyzed at or near the first outlet 404 and/or the second outlet 405. In some embodiments, separated particles are collected, detected, counted, or otherwise analyzed at or near the first outlet 404. In some embodiments, particles of different masses are collected at or near the first outlet 404 and/or the second outlet 405. In some embodiments, at least one of the outlets 404, 405 can be connected to ports or to other coupling devices (e.g. configured to mate with a syringe) to allow a solution to exit the spiral separation structure 400. In some embodiments, the spiral fluidic channel 403 can be configured to receive a first fluid at the first inlet 401 and a second fluid at the second inlet 402. In some embodiments, the spiral channel 403 can be further configured to draw at least a portion of particles suspended in the second fluid from the second fluid into the first fluid based on molecular mass. FIG. 4B is an illustrative diagram of particle separation as a particle-containing fluid traverses a spiral particle separation structure 400, according to an embodiment. In some embodiments, particles of a substance suspended in a fluid enter the spiral separation structure 400 at the second inlet 402 and are located at or near the inner wall of the spiral. As the fluid traverses the loops of the spiral channel 403, separation of at least a portion of particles begins to occur based on molecular mass, with larger particles (Particle #2) migrating to a location near the inner wall of the spiral channel 403 and smaller particles (Particle #1) being drawn to a location near an outer wall of the spiral channel 403. At or near the second end of the spiral 403, at least a portion of the smaller particles (Particle #1) are separated: larger particles (Particle #2) are in an equilibrium position located near the inner wall of the spiral channel 403, and at least a portion of smaller particles (Particle #!) are drawn to a location near an outer wall of the spiral channel 403. In some embodiments, the first outlet 404 can be configured to receive a first fluid including the portion of the drawn particles, and (in some embodiments) the second outlet 405 can be can be configured to receive the second fluid. Without being limited by theory, fluid flowing through a spiral fluidic channel (e.g., the spiral channel illustrated in FIG. 4 A) experiences centrifugal acceleration directed radially outward, which leads to the formation of two counter-rotating vortices known as Dean vortices in the top and bottom halves of the channel, as illustrated in FIG. 4B. The magnitude of these secondary flows in the two counter-rotating vortices can be quantified by a dimension less Dean number (De), shown in equation 1 : Equation 1:

where p is the density of the fluid medium (kg/nr¹), U_f is the average fluid velocity (m/s), μ is the fluid viscosity (kg/(m -s)), R is the radius of curvature (m) of the path of the spiral fluidic channel, and Re is the flow Reynold number. For a straight fluidic channel, De = O, indicating the absence of Dean flows. In curved channels, De increases with higher curvature (smaller R), larger channel size (D ), and faster flows (higher Re). Particles flowing in a curvilinear channel experience a drag force due to the transverse Dean flows. Depending on particle size, this drag force, also known as Dean force (F_D), shown in equation 2, which can cause particles to move along the Dean vortices (i.e. circulate), and thus move towards either the inner channel wail or the outer channel wall.

F_D = 3πμυ_0βαηα_ρ = 5.4 x 1G^~4 x μΟβ³-^β3α_ρ where a_p is the particle size and Uoean is the average Dean velocity, which is 1.8 x 10^→De ^iAj (m s^"1). In addition to Dean force (F_D), particles in a curvilinear channel experience pressure forces and mertial lift forces. The net lift force (F_L), shown in equation 3, acting on a particle is a combination of shear induced mertial lift force and channel wall-induced mertial lift force.

F_L=pG²Cia * where G is the shear rate of the fluid is^"1 ) and C_L is the lift coefficient, which is a function of the particle position across the channel cross-section, assuming an average value of 0.5. The average value of G for a Poiseuiile flow is given by G = U max D_h, where, U_raax is the maximum fluid, velocity (m s-1 ) and can be approximated as 2 x U_f.. In Poiseuille flow, the parabolic nature of the velocity profile results in a fluidic shear- induced mertial lift force that acts on particles and is directed away from the fluidic channel center. As the particles move towards fluidic channel walls, an asymmetric wake induced around ceils generates a wail-induced inertia! lift force away from the walls. The magnitude of these opposing forces varies across fluidic channel cross-sections, with wall-induced lift forces dominating near the fluidic channel walls (e.g., inner wail and outer wall in FIG. 4B) and the shear-induced lift forces dominating near the center of the fluidic channel. The particles thus tend to occupy equilibrium positions where the oppositely directed lift forces are equal and form narrow bands. FD and FL depend on the particle size (<¾,), with the lift force (FL) increasing rapidly for increasing particle size (FL « _p ⁴ while FD O <¾). By varying the ratio of these two forces, differential migration of particles based on size (i.e. mass) can be used to achieve separation. In some embodiments, the size dependence of the forces that act on particles flowing in a spiral fluidic channel 403, namely the Dean force (FD) and the inertial lift forces (FL), can be manipulated to produce focused streams of particles of simi lar sizes, in some embodiments, the Dean force (F_D) and the inertial lift forces (FL) can produce two or more streams, a first stream near the outer wall of the channel, which (in some embodiments) includes smaller particles (Particle #1), and a second stream, which (in some embodiments) includes larger particles (Particle #2). The larger particles (Particle #2), in some embodiments, can be particles with a mass greater than a first mass. The smaller particles (Particle #1), in some embodiments, can be particles with a mass less than a first mass, In some embodiments, inertial lift forces and viscous drag forces acting on particles of various sizes suspended in a fluid flowing through the channel induces differential migration of particles and, thus, separation of at least a portion of the particles. In some embodiments, spiral inertial forces, namely lift force (FL) and Dean drag force (FD), due to the spiral geometry, can cause larger particles (Particle #2) to occupy an equilibrium position near the inner wall of the spiral channel 403, as shown in FIG. 4B, The spiral geometr of the spiral particle separation structure can, in some embodiments, cause smaller particles (Particle #1) to experience higher viscous drag due to Dean flows, and the smaller particles will continue to re-circulate along the Dean vorticies and can be transposed to the outer half of the fluidic channel 403, as shown in FIG. 4B. In some embodiments, due to the spiral geometry, small particles (Particle #1), under the influence of Dean drag force (F_D), can migrate to the outer wall of the channel 403 by diffusing away from a stream located near the inner wall and into a stream located near the outer wall. Accordingly, in some embodiments, spiral inertia! forces can produce at least two distinct particle streams, as shown in FIG. 4B, which are directed to, and may be collected at or near, corresponding outlets. Thus, in some embodiments, a spiral particle separation structure 400 can use inertia! migration of larger particle (Particle #2) and the influence of Dean force (FD) on small particles (Particle #1) to achieve separation of at least a portion of smaller particles (Particle #1). Still referring to FIGS. 4A-4B, in some embodiments, the design of the spiral separation structure 400 includes a spiral geometry. A spiral geometry can be defined as a curve on a plane that winds around a fixed center point at a continuously increasing or decreasing distance from the center point. In some embodiments, a spiral can deviate from the plane in a third dimension and can (in some embodiments) resemble a cone shaped spring. Non-limiting examples of a spiral geometry include an exponential geometry, an Archimedean geometry, a hyperbolic geometry, a logarithmic geometry, a parabolic geometry, and the like. In some embodiments, the spiral particle separation structure 400 can include one or more loops. One loop can be defined as about one complete circle (e.g. one complete spiral, about 360 degrees) around the center point of the spiral separation structure 400. FIG. 4A illustrates 5 loops, but in other embodiments (not shown), the spiral separation structure 400 includes about 1 or more loops, about 2 or more loops, about 3 or more loops, about 4 or more loops, about 5 or more loops, about 6 or more loops, about 7 or more loops, about 8 or more loops, about 9 or more loops, or about 10 or more loops. In some embodiments, the spiral separation stracture 400 includes between about 2 and about 100 loops, between about 2 and about 75 loops, between about 2 and about 50 loops, between about 2 and about 25 loops, between about 2 and about 20 loops, between about 2 and about 10 loops, between about 2 and about 5 loops, between about 2 and about 3 loops, including all values and subranges in between. In some embodiments, a spiral separation stracture includes about 1 , about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20 or more loops. The number of loops can influence the efficiency of separation, and different numbers of loops can be suitable for separating different particles from different fluids. For example, fewer loops can be used if lower separation efficiency is desired, and more loops can be used if substantially complete separation is desired. FIG. 5A depicts an illustrative, non- limiting embodiment of a spiral separation structure 500 with a 5-loop spiral channel 501 , an outer inlet 502, an inner inlet 503, an outer outlet 504, and an inner outlet 505. In some embodiments, a spiral separation structure includes a 3 -loop spiral geometry with two or more inlets and two or more outlets. For example, FIG. 5B depicts an illustrative, non-limiting embodiment of a spiral separation structure 500' with a 3-loop spiral channel 501 ', an outer inlet 502 ', an inner inlet 503 ', an outer outlet 504' and an inner outlet 505 ' . In some embodiments, the channel (e.g., the channel 500 and/or the channel 500') includes one or more loops formed as a logarithmic spiral . A logarithmic spiral can be defined by the following equation: r = ae^W wherein the spiral has polar coordinates (r, Θ), where r is a distance from the origin of the spiral, Θ is an angle from an x-axis, and e is the base of Natural Logarithms, and wherein the spiral has arbitrary positive real constants, a and b, where a is a growth factor of geometric progression defined by the relationship between the spacing of loops of the spiral, and b = cot(cp), (M nteanu, MI, J. Math. Phys. 2010:51 ;073507). φ can be defined as the angle between a radial direction of a curve of a logarithmic spiral and its tangent line. Logarithmic spirals can be defined by the property that the curve is oriented such that there is a constant angle φ between a tangent line and the radial direction of the curve at the point (r, Θ). Additionally, a logarithmic spiral can be defined by the property that the distance between successive loops changes in a geometric progression. Geometric progression can be characterized as the distance between loops measured on a straight line drawn from a center point of the spiral, where the distance between successive loops can change by a substantial ly constant factor. In some embodiments, the geometric progression of spacing between loops (a) of is about 0.1 , about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1 , about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10, including all values in between. In some embodiments, the geometric progression of spacing between loops (a) is about 0.5, about 0.55, about 0.6, about 0,65, about 0.7, about 0.75, about 0.8, about 0.85, about 0.9, about 0.95, about 1 .1 , about 1.2, about, 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2, including all values in between. For example, if, in some embodiments, the spacing between a first loop and a second loop is about 1 mm, where the first loop and the second loop are located near the outer point of the spiral, and the spacing between successive loops decreases in geometric progression by a factor of 0.75, then the spacing between the second loop and the third loop is about 0.75mm, Referring again to FIGS 4A-4B, in some embodiments, the spacing between two successive loops of the spiral separation structure 400 is about 1 μηι or more, about 10 μηι or more, about 100 um or more, about 200 μ,ηι or more, about 250 um or more, about 300 um or more, about 400 um or more, about 450 μπι or more, about 500 um or more, about 550 μαι or more, about 600 μτη or more, about 650 um or more, about 700 μτη or more, about 750 μτη or more, about 800 urn or more, about 850 μιη or more, about 900 urn or more, about 950 μπι or more, or about 1mm, including all values and sub-ranges in between. In some embodiments, the spacing between two successive loops of the spiral separation 400 structure is about 1 μπι to about 100 mm, about I μιη to about 10 mm, or Ιμπι to about I mm, including all values and sub- ranges in between. In some embodiments, the spacing between a first loop and a second loop is about 1 mm, where the first loop is the outermost loop of a spiral. In some embodiments, the initial radius of curvature (R) of a spiral is about 1 mm to about 10 mm, including all values and sub-ranges in between. In some embodiments, the initial radius of curvature (R) is about 2 mm, about 3 mm, about 4 mm, or about 5 mm, including all values in between. In some embodiments, the length of the spiral fluidic channel is about 2 cm or more, about 4 cm or more, about 6 cm or more, about 8 cm or more, about 10 cm or more, about 12 cm or more, about 14 cm or more, about 16 cm or more, about 18 cm or more, about 20 cm or more, or about 22 cm or more, including all values and sub-ranges in between. In some embodiments, the length of the fluidic channel is between about 2 cm and about 50 cm, between about 2 cm and about 40 cm, between about 2 cm and about 30 cm, between about 2 cm and about 25 cm, between about 2 cm and about 20 cm, between about 2 cm and about 15 cm, or between about 2 cm and about 10 cm, including all values and sub-ranges in between. In some embodiments, the length of a fluidic channel is about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, about 10 cm, about 1 1 cm, about 12 cm, about 13 cm, about 14 cm, about 15 cm, about 16 cm, about 17 cm, about 18 cm, about 19 cm, about 20 cm, about 21 cm, about 22 cm, about 23 cm, about 24 cm, about 25 cm, about 26 cm, about 27 cm, about 28 cm, about 29 cm, or about 30 cm, including all values and sub-ranges in between. One skilled in the art wi ll recognize that the length of the fluid channel 403 can be adjusted to achieve different separation efficiencies, where greater separation efficiencies c achievable with longer channel lengths, In some embodiments, the spiral fluidic channel 403 has an outer diameter between about 50 mm to about 10 cm, including ail values and sub-ranges in between. In some embodiments, the spiral fluidic channel has an inner diameter between about 20 mm to about 2 mm, including all values and sub-ranges in between. In some embodiments, the spiral fluidic channel has an outer diameter of about 17.8 mm. and, in some embodiments, an inner diameter of about 7.8 mm. FIG. 6 depicts an illustrative, non-limiting embodiment of a spiral separation structure 600 with a spiral channel 605 formed as a 5 loop logarithmic spiral. In some embodiments, a first fluid, enters the spiral separation structure 600 at a first inlet 601 and passes through a first, inlet channel 603 to reach the spiral channel 605. In some embodiments, a second fluid enters the spiral separation structure 600 at a second inlet 602 and passes through a second inlet channel 604 to reach the spiral channel 605. in some embodiments, the spiral channel 605 includes 5 loops formed as a logarithmic spiral, where the spacing between successive loops changes in geometric progression by a factor of about 0.75 when measured from outside of the spiral to inside of the spiral. In some embodiments, the spiral channel 605 has an outer diameter of about 17.8 mm and an inner diameter of about 7.8 mm. In some embodiments, the first fluid traverses the first outlet channel 606 and exits the spiral channel 605 at the first outlet 608. In some embodiments, the second fluid traverses a second outlet channel 607 and exits the spiral channel 605 at the second outlet 609. Fluid/FIuidic channels In some embodiments, a separation device, spiral separation structure, separation system, detection system, and/or mixing structure includes one or more fluidic channels. In some embodiments, the fluidic channel can be a microfluidic channel. In some embodiments, the fluidic channel (s) can be embedded in a chip. In some embodiments, the fluidic channel can be configured to contain a dynamic fluid (e.g. moving fluid or solution) that can include particles. In some embodiments, the particles can be cells (e.g. prokaryotic ceils, a eukaryotic cells, human cells, and/or the like), where at least a portion of the cells can be lysed to liberate metabolites. The fluidic channel can be made of any suitable material. The cross section of a fluidic charmei can be of any suitable shape (e.g. rectangular or circular). In some embodiments, a fluidic channel includes a first end and a second end. In some embodiments, a fluidic channel includes a first end, and the first end includes and/or is associated with a valve, a port, a flow regulator, and/or at least one inlet. In some embodiments, a fluidic channel includes a second end, and the second end includes and/or is associated with a valve, a port, a flow regulator, and/or at least one outlet. In some embodiments, a first end and/or second end can be configured to provide a continuous channel between a source, a pump and valve system, a mixing structure, a detector, and/or the like, including combinations thereof. In some embodiments, the fluidic channel is formed as a spiral. In some embodiments, the spiral has a first end and a second end . In some embodiments, the first end can be closer to the outer point of the spiral relative to the second end. In some embodiments, the first end can be closer to the center of the spiral channel relative to the second end. In some embodiments, the first end of the spiral fluidic microchannel can be fluidly coupied to a first inlet and to a second inlet. Referring to FIG. 6, the first end includes a first inlet 601 (also referred to as an "outer inlet") and a second inlet 602 (also referred to as an "inner inlet") located at the first end of the spiral channel 605, where the first end is located close to the outer point of the spiral channel 605. In some embodiments, the first inlet 601 can include a first inlet port (not shown) that can be configured to fluidly couple a source of a first fluid, and (in some embodiments) the second inlet 602 can include a second inlet port, (not shown) that can be configured to fluidly couple a source of the second fluid. In some embodiments, the source can be a fluid sample or an organism (not shown). In some embodiments, a needle can be used to mate with the source (not shown), in some embodiments, the needle can be a microneedle (e.g., see McAllister, DV, et. al., PNAS. 25 Nov 2003: 100(24); 13755-13760; Henry, S. et. al. J. of Pharm. Sci. 26 Jim 1998:87(8);922-25). In some embodiments, the first inlet port and/or the second inlet port can be configured to fluidly couple a pump to provide at least one of the first fluid or the second fluid to the first inlet 601 or the second inlet 602, respectively. In some embodiments, the inner diameter of the fluidic channel 605 can be about 0.2 μπι to about 2000 μιη, or about 10 μιη to about 1000 μπι, including all values and sub-ranges in between. In some embodiments, the inner diameter of the fluidic channel 605 is about 250 μηι to about 500 ,um, including all values and sub-ranges in between. In some embodiments, the inner di ameter of the fluidic channel is about 250 p.m. in some embodiments, the inner diameter of the fluidic channel is about 500 μηι. Referring to FIG. 6, an illustrative, non-limiting embodiment of a spiral separation structure 600 with the fluidic channel 605 having an inner diameter of about 500 μτη is depicted. In some embodiments, the fluidic channel 605 is a diffusion channel in which the first fluid and the second fluid flow^r in parallel, where spiral inertia! forces can act on particles suspended in the second fluid to draw at least a portion of particle suspended in the second fluid are drawn into the first fluid. In some embodiments, the diffusion channel 605 includes the first inlet channel 603 that can be fluidly coupled to the first inlet 601 and to a first end of the diffusional channel 605, and (in some embodiments) the second inlet channel 604 that can be fluidly coupled to the second inlet 602 and to a second end of the diffusion channel 605. In some embodiments, the diffusion channel 605 can include the first outlet channel 606 that can be fluidly coupled to the first outlet and to the second end of the diffusion channel 605. In some embodiments, the diffusion channel 605 can include the second outlet channel 607 that can be fluidly coupled to the second outlet 608 and to the second end of the diffusion channel 605. In some embodiments, the first outlet channel 606 and/or the second outlet channel 607 can be arranged as cundlinear outlet channels relative to the diffusion channel 605. In some embodiments, the first cundlinear outlet channel 606 can be configured to receive particles drawn into a first fluid from a second fluid, and (in some embodiments) the second curvilinear outlet channel 607 can be configured to receive the second fluid. In some embodiments, the first inlet channel 603 fluidly couples a first inlet 601 to a fluidic spiral channel 605. In some embodiments, a second inlet channel 604 fluidly couples a second inlet 602 to the fluidic spiral channel 605. In some embodiments, the first inlet channel 603 and/or the second inlet 604 channel has an inner diameter of about 250 μτη. In some embodiments, a first outlet channel 606 fluidly couples a first outlet 608 to the fluidic spiral channel 605. In some embodiments, a second outlet channel 607 fluidly couples a second outlet 609 to the fluidic spiral channel 606. In some embodiments at least one of the first outlet channel 606 or the second outlet channel 607 are arranged as curvilinear outlet channels. In some embodiments, the first outlet channel 606 and/or the second outlet channel 607 has an inner diameter of about 250 μχη. In some embodiments, the inner diameter of a fluidic inlet and/or outlet channel can be about 0.2 μνα to about 2000 μνα or about 10 urn to about 1000 μηι. In some embodiments, the inner diameter of a fluidic inlet and/or outlet channel is about 250 μηι to about 500 μχη. In some embodiments, the inner diameter of a fluidic inlet and/or outlet channels are about 250 μπι, In some embodiments, at least one of the inlets and/or outlets can include ports. In some embodiments, inlet and/or outlet ports can be configured to fluidly couple a fluidic channel to a source, a pump and valve system, a mixing structure, and a detector, the like and/or combinations thereof. In some embodiments, inlet and/or outlet ports can be configured to mate with a needle. In some embodiments, the needle can be a microneedle (McAllister, DV, et. al., FN AS 25 Nov 2003 : 100(24); 13755-13760; Henry, S. et. al. J. of Pharm. Sci. 26 Jun 1998:87(8);922-25). In some embodiments, inlet and/or outlet ports can be about 1 μηι to about 100 mm in diameter or about 1 mm to about 10 mm in diameter. In some embodiments, inlet and/or outlet ports can be about 2,54 mm in diameter, Detector In some embodiments, at least one of the first outlet (e.g., the first outlet 608) or the second outlet (e.g., the second outlet 609) can be configured to fluidly couple a detector (e.g., the detector 712, described later) for the sorted particles. In some embodiments, the detector is provided. A detector can be any device that can be used to detect or measure a characteristic of a sorted particle. In some embodiments, the detector detects the signal transmitted from the sorted particles. In some embodiments, the detector detects the presence, absence, and/or amount of a particle. Non-limiting examples of devices that can be used to detect sorted particles includes, but are not limited to, the following: a mass spectrometer, a spectroscopic device (e.g., terahertz spectroscopy), nuclear magnetic resonance, a microfiuidic detector (e.g., thermal particle detector, electrokinetic microfiuidic chip, and/or the like), biosensor, and/or the like. In some embodiments, the detector is a mass spectrometer. Non-limiting examples of suitable mass spectrometers (MS) include, but are not limited to, the following: time-of-flight MS, quadrupole MS, ion trap MS, ion cyclotron resonance MS, electrospray ionization MS, monolithic M EMS Quadrupole (Geear, M, et. al, I EEE. 1 0 Oct 2005; 14(5): 1 156 - 66), and/or the like, Referring again to FIG. 6, in some embodiments, the detector can be fluidly coupled to at least one of the first outlet 608 or the second outlet 609. In some embodiments, the detector can be configured to detect particles suspended in a fluid received at the first outlet 608 and/or the second outlet 609, respectively. In some embodiments, as illustrated in FIG. 10A, the detector can be fluidly coupled to the first outlet 608 of a device (e.g., the spiral separation structure 600) and (in some embodiments) the detector can be configured to detect particles drawn into the first fluid from the second fluid, such that particles drawn into the first fluid exit the device at the first outlet 608. Pump To traverse the spiral separation structure 600, particles suspended in a fluid can be provided to the spiral separation structure 600 at a certain flow rate. In some embodiments, a pump is used to provide fluid to the spiral separation structure 600. In some embodiments, the degree of particle separation is a function of the velocity at which a particle suspended in a fluid traverse the spiral separation stracture 600. In some embodiments, the pump provides fluid at a controllable velocity. In some embodiments, the pump is configured to pull a fluid from a source and to provide the fluid to the spiral separation stracture 600. In some embodiments, the pump is configured to provide the fluid in a manner in which the droplet size, periodicity, and/or flow rate can be controlled. In some embodiments, for continuous monitoring of a sample over time, fluids need to be provided to a separation device at different time points. In some embodiments, the pump is configured to provide fluid at a substantially constant droplet size, periodicity, and/or rate. In some embodiments, the pump can be attached to, embodied on, or embedded in a chip (e.g. a iab-on-a-chip, and/or the like). In some embodiments, the pump can be a modular system that can be fluidly coupled to a device (e.g. mixing stracture, separation structure, and the like). In some embodiments, control of the pump is automated . In some embodiments, operation parameters for the pump can be set according to instructions programmed into pump. Valve In some embodiments, a valve can interface a source of a fluid (e.g., with a mixing structure, with the spiral separation structure 600, with a pump, and the like). In some embodiments, a valve can be used to permit fluid flow from a source to a device (e.g., a mixing structure, a spiral separation structure 600, a pump, and/or the like). In some embodiments, the valve can be configured to, in a first setting, permit fluid flow from the source to the pump. In some embodiments, the valve can be further configured to, in a second setting, permit fluid flow 11 ffroromm tthhee ppuummpp ttoo tthhee ssppiirraall sseeppaarraattiioonn ssttrruuccttuurree 660000.. IInn ssoommee eemmbbooddiimmeennttss,, aa ffuunnccttiioonn ooff tthhee

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16 FIGS. 7A and 7B schematically depict an illustrative and non-limiting embodiment of

17 components of a separation system, including a pump 700, a valve 701, a spiral separation

18 structure 709, which can be similar to the separation structure 605. The spiral separation

19 structure 709 has a first inlet 707, a second inlet 708, a first outlet 710, and a second outlet 71 1.

20 The first outlet 710 is fluidly coupled to a detector 712, and the second outlet is fluidly coupled

21 to a waste receptacle 713, The pump 700 and the valve 701 are further fluidly coupled to a first

22 source 703, a second source 705, and a third source 714. The second source 705 and the third

23 source 714 are further fluidly coupled to a mixing structure 706. In some embodiments, the

24 pump 700 is operably coupled to a first syringe 702 and a second syringe 704.

25 In the first setting (FIG. 7 A), the pump 700 is configured to pull/draw a fluid (e.g., a

26 biological fluid, a reagent, and/or the like) from at least one of the sources 703, 705, and/or 714

27 and to, in a second setting (FIG. 7B), the pump 700 is configured to provide the fluid to the spiral

28 separation structure 709. As illustrated in FIG. 7 A, in some embodiments, the pump 700 can be

29 configured to fluidly couple to at least one of a first source 703 of the first fluid, the second

30 source 705 of a second fluid, or (in some embodiments) a third source 714 of a third fluid. In some embodiments, the valve 701, in the first setting, is configured to permit fluid flow from at least one source 703, 705, and/or 714 to the pump 700 such that the pump can pull/draw at least one fluid from the source. As illustrated in FIG 7B, the valve 701 , in the second setting, is configured to permit and/or facilitate fluid flow from the pump 700 to the spiral separation structure 709. In some embodiments, the pump 700 can be further configured to fluidly couple to the first inlet 707 and to the second inlet 708 of the separation structure 709. In some embodiments, the pump 700 can be configured to pull the first fluid from the first source 703 and the second fluid from the second source 705 (e.g., in the first setting). In some embodiments, the pump 700 can further be configured to provide the first fluid to the first inlet 707 and the second fluid to the second inlet 708 of the separation structure 709 (e.g., in the second setting). In some embodiments, the pump 700 is a dual syringe pump. In some embodiments, as illustrated in FIG. 7A and 7B, the pump 700 includes a first syringe 702 and a second syringe 704 operably coupled to the valve 701. In some embodiments, the first syringe 702 can be configured to receive the first fluid pulled from the first source 703, and the second syringe 704 can be configured to receive the second fluid pulled from the second source 705 (see FIG. 7 A). In some embodiments, the first syringe 702 can be further configured to provide the first fluid to the first inlet 707, and the second syringe 704 can be further configured to provide the second fluid to the second inlet 708 (see FIG. 7B). In some embodiments, as illustrated in FIG. 7 A, the pump 700 and the valve 701 can be further configured such that, in the first valve position (i.e., in the first setting), the pump further pulls a third fluid from a third source 714. In some embodiments, the second syringe 704 can be further configured to receive at least one of the second fluid and/or a third fluid pulled by the pump 700. In some embodiments, the pump 700 can further be configured to provide at least one of the second fluid, and/or the third fluid to the second inlet 708 of the device 709. For example, in some embodiments, the second fluid is a cell suspension and the third fluid is a cell lysis solution. Accordingly, in some embodiments, a function of the pump 700 is to pull both the second fluid (e.g. cell suspension) from the second source 705 and the third fluid (e.g. cell lysis solution) from the third source 714, where the second syringe 704 can be configured to receive both the second fluid and the third fluid (see FIG. 7A). In a further embodiment, the pump 705 can be further configured to provide both the second fluid and the third fluid to the second inlet 708 (see FIG, 7B). Controller In some embodiments, a controller (not shown in FIG, 7) can be configured to operate different components of a separation system (e.g., the pump 700, the valve 701, the separation structure 709, the detector 712, and/or the like). In some embodiments, the pum 700 and the valve 701 system can be controlled by the controller, as shown in FIGS. 10A and 10B. Furthermore, as best illustrated in FIG. 10B, the controller 1013' can be configured to control at least one of the pump 1008', the vaive 1009', a mixing structure 1004', the first source 1010' of the first fluid, the second source 1011 ' of the second fluid, the third source 1016' of the third fluid, the separation structure 1015', the detector 1012', and/or the like. In some embodiments, the controller is an active controller or a passive controller. In some embodiments, control of the pump 700 and the valve 701 system is automated, wireless, and/or cloud-based. In some embodiments, operation parameters for the pump 700 and the valve 701 system can be set according to instructions programmed into the pump. For example, in a non-limiting embodiment, the controller is an in-house computer program designed with Labview (National Instruments), In some embodiments, control of the pump 700 is synchronized with the valve 701 using the in-house computer program designed with Labview (National Instalments). In some embodiments, the controller includes at least a processor and/or a memory. Mixing Structure The diminutive scale of flow channels in microfluidic systems increases the surface to volume ratio, and is therefore advantageous for many applications. However, the specific Reynolds number (Re = I ρν/η) of liquid flows in such fluidic channels is very small. For example, the Reynolds numbers is of the order of 0.1 in a typical water-based microfluidic system with a channel width of 100 μιη, a liquid flow rate of 1 mm/s, a fluid density of 1 g/cm^~, and a viscosity of 0.001 Ns/m². In such low Reynolds number regimes, turbulent mixing does not occur, and hence diffusive species mixing plays an important role, but is an inherently slow processes. In some embodiments, a mixing structure is configured to enhance mixing of fluids such that substantially thorough mixing can be achieved, in some embodiments, a function of the mixing structure is to shorten mixing times. In some embodiments, a function of the mixing stmciure is to mix two fluids such that thorough mixing is achieved prior to providing the fluids to the separation system 709. In some embodiments, a function of the mixing structure is to mix a cell suspension with a lysing solution such that particles (e.g., metabolites) are liberated from the cells. In some embodiments, a function of the mixing structure is to shorten the length of the diffusion channel 605 and to reduce the overal l size of the separation and detection system, in some embodiments, an efficient mixing structure is employed for increasing the throughput of the separation and detection system and to enable an effective lab-on-a-chip system. In some embodiments, the mixing stmciure includes fluidic channels. In some embodiments, the mixing system can be attached to, embodied on, or embedded in a chip (e.g., a iab-on-a-chip, and/or the like). In some embodiments, the mixing structure can be a modular system that can be fluidly coupled to a separation structure, such as the separation structure 709 and/or 60. In some embodiments, the mixing structure is an active fluidic mixer. Non-limiting examples of active fluidic mixers include acoustic mixers, ultrasonic mixers, dielectrophoretic mixers, electrokinetic time-pulse mixers, pressure perturbation mixers, magnetic mixers, thermal mixers, electrohydrodynamic force mixers, magneto-hydrodynamic flow mixers and/or electrokinetic instability mixers, and/or the like, and combinations thereof. In some embodiments, the mixing structure is a passive fluidic mixer. Non-limiting examples of a passive fluidic mixer include lamination mixers (e.g. wedge shaped inlets, 90 degree rotation), zigzag channels (e.g. elliptic-shape barriers), serpentine mixing channels, 3D serpentine structures (e.g. folding structure, creeping stmciure, stacked shim structure, multiple splitting and stretching, recombining flows, unbalanced driving force), embedded barriers (e.g. SVIX. multidirectional vortices), twisted channels (e.g. split and recombine), and/or surface chemistry (e.g. obstacle shape, Τ-/Ύ- mixers), the like and/or combinations thereof. In some embodiments, the mixing structure is a microfluidic mixing tee (e.g. a T -mixer, a Y -mixer, and/or the like). The microfluidic mixing tee can be configured to combine two or more fluid streams to cause turbulent mixing of the two fluids. In some embodiments, the microfluidic mixing tee is a Y-valve 800 as shown in FIG 8. In some embodiments, the Y-valve 800 includes two inlets 801a and 80 lb located at the bifurcated end of the valve, a mixing channel 802 which combines the two fluids, and an outlet 803 located at the opposite end of the mixing structure as the inlets 801a and 801b. In some embodiments, the inlets 801a and 801b can include inlet ports (not shown) which can be configured to fluidly couple the two inlets 801a and 801b to sources of the fluids. In some embodiments, the outlet 803 can be configured to provide a mixed stream in which the two fluids have been turbuiently mixed. In some embodiments, the outlet 803 can include a port (not shown) that can be configured to fluidly couple the outlet to the valve 701 , the pump 700, the separation structure 709, and/or the like. For example, in some embodiments, as illustrated in FIG. 7 A, the pump 700 pulls the first fluid from the first source 703, the second fluid from the second source 705, and the third fluid from the third source 714, The first fluid is received by the first syringe 702 operably coupled to the pump 700. The second fluid and the third fluid, prior to being received by the second syringe 704, enters the mixing structure 706, such as the mixing structure 800 (also referred to as the "Y-valve") of FIG. 8. In some embodiments, the second fluid enters the Y- valve 800 at a first inlet 801 a, the second fluid including particles of a substance suspended therein, and a third fluid enters the Y-valve 800 at the second inlet 801b. In some embodiments, the second fluid includes cells. In some embodiments, the third fluid is a ceil lysis solution. In some embodiments, the second fluid and the third fluid are combined in the mixing channel 802 of the Y-valve 800 such that turbulent mixing of the second fluid and the third fluid occurs. In some embodiments, a mixed fluid stream leaves the mixing structure at the outlet 803. Fluid Coupling To fluidly couple the components of the system (e.g., fluid coupling of the pump 700 to the valve 701, the spiral separation structure 709, the mixing structure 706, the detector 712, and/or the fluid sources 703, 705, and 714, and/or fluid coupling of the spiral separation structure 709 to the detector, and/or the like), tubing can be used. The tubing can be of appropriate material, length, and diameter as necessary and/or sufficient for generating and/or maintaining flow into the device. In some embodiments, the tubing is PEE ^ijVl (polyetheretherketone) tubing. In some embodiments, PEEK.^{13 1} tubing with 1/32 in. outer diameter and 0.005 mm inner diameter can be used for fluid coupling. FIG. 11 A illustrates a non-limiting embodiment of PEEK™ tubing 110.1 to fluidly couple a syringe 1103 to a needle .1.102, which can be mated to an inlet port. For example, in some embodiments, the PEEK ^iM tubing 1101 can be threaded into the needle 1102 of appropriate dimensions, and PDMS can be cured into the top of the needle 1102 to create a seal.. One skilled in the art can appreciate that the length and diameter of tubing may vary depending on the sample, flow rate, injection volume, and/or the like. Accordingly, referring again to FIGS. 7 A. and 7B, ΡΕΕΚ^ΐΛί tubing can configured to fluidly couple the pump 700 to the first inlet 707 and the second inlet 708 of the device using syringe needles, pipette tips, and/or the like, and/or combinations thereof. To mate with the inlet port (e.g., the port of the inlet 707 and/or the port of the inlet 708), in some embodiments, a syringe needle can be used. Referring now to FIG. 1 I B, an illustrative and non-limiting embodiment of an inlet 1104 with an inlet port configured to make with a needle 1 102 is depicted. For example, in some embodiments, inlet ports can be configured with an appropriate diameter (e.g., about 2.54 mm) and height (e.g., from about 10 to about 12 μπι) to mate with syringe needle (e.g., 18 gauge needle). In some embodiments, the needle 1102 can be modified to mate with inlet ports. For example, FIG. 11A illustrates an embodiment of the modified needle 1102 configured to mate with an inlet port of a height of about 10 to about 12 μπι. For example, in some embodiments, the tip of the needle (e.g.18 gauge needle) 1102 may be ground down to produce a flat end which can be inserted into an inlet 1 104 of the device 1105. Device FIG. 9A depicts an illustrative and non-limiting embodiment of a device 900 for separating particles. In some embodiments, device 900 includes a first inlet 901 that can be configured to receive a first fluid. In some embodiments, device 900 includes a second inlet 902 that can be configured to receive a second fluid having particles of a substance suspended therein. The first inlet 901 and the second inlet 902 can be independently and suitably designed for accepting particles to be analyzed. For example, the cross-sectional shape and area of the first inlet 901 and/or the second inlet 902 can be matched to pipette tips. In some embodiments, device 900 includes a channel 903 that includes one or more loops formed as a spiral. In some embodiments, the channel 903 includes a first end and a second end, the first end being closer to an outer point of the logarithmic spiral relative to the second end. In some embodiments, the channel 903 can be fluidly coupled to the first inlet 901 and to the second inlet 902 at the first end. In some embodiments, the channel 903 can be configured to receive the first fluid from the first inlet 901 and the second fluid from the second inlet 902. In some embodiments, the channel 903 can be further configured to draw at least a portion of the suspended particles from the second fluid into the first fluid based on a characteristic of the suspended particles. In some embodiments, the characteristic of the drawn particles includes diameter or molecular mass. In some embodiments, the characteristic of the drawn particles is molecular mass. In some embodiments, a first outlet 906 can be fluidly coupled to the second end of the channel 903, the first outlet 906 can be configured to receive the first fluid, including the portion of drawn particles. In some embodiments, a second outlet 907 can be fluidly coupled to the second end of the channel 903, the second outlet 907 configured to receive the second fluid. The outlets 906 and 907 can be independently designed based on application needs, such as, for example, including a reservoir for temporary storage of separated particles, coupling to an enrichment structure, an interface for withdrawal of the separated particles, and/or the like.

In some embodiments, at least a portion of the device 900 is fabricated from one or more non-conductive polymeric materials. In some embodiments, at least a portion of the device 900 is fabricated from one or more of poly-dimethylsiloxane or thermoplastics.

In some embodiments, the channel 903 is formed as a logarithmic spiral with polar coordinates (r, Θ) and a logarithmic curve (r) of the logarithmic spiral defined as:

r = ae^b0 In some embodiments, the channel 903 includes about 1 loop to about 5 loops. In some embodiments, the one or more loops of the channel 903 includes a plurality of loops, the plurality of loops including a spacing between successive loops. The spacing between successive loops can be measured from outside of the spiral to inside of the spiral, and can change in geometric progression by a factor of about 0.75. In some embodiments, the channel 903 has a width of from about 1 nm to about 1 mm. In a further embodiment, the channel 903 has a width of about 500 μ,ηι. In some embodiments, the channel 903 has a length such that the portion of the suspended particles are drawn from the second fluid into the first fluid. In some embodiments, the channel 903 has a length of from about 5 cm to about 25 cm. In some embodiments, the channel 903 has an outer diameter of about 10 mm to about 18 mm and an inner diameter of about 8 mm. In some embodiments, the first inlet 901 includes a first inlet port that can be configured to fluidly couple a source of the first fluid. In some embodiments, the second inlet 902 includes a second inlet port configured to fluidly couple a source of the second fluid. In some embodiments. the at least one of the first inlet port or the second inlet port can be configured to fluidly couple a pump for one or more of the first fluid or the second fluid. In some embodiments, the first outlet 906 includes a first outlet port, and (in some embodiments) the second outlet 907 includes a second outlet port. In some embodiments, at least one of the first outl et port or the second outlet port can be configured to fluidly couple a detector for the particles. In some embodiments, the channel 903 is a diffusion channel, the diffusion channel 903 can include a first inlet channel 904. The first inlet channel 604 is fluidly coupled to the first inlet 901 and to the first end of the diffusion channel 903. In some embodiments, the diffusion channel 903 further includes a second inlet channel 905. The second inlet channel 905 is fluidly coupled to the second inlet 902 and to the first end of the diffusion channel 903. In some embodiments, the at least one of the first inlet channel 904 or the second inlet channel 905 has a width of from about 1 nm to about 1 mm. In some embodiments, the at least one of the first inlet channel 904 or the second inlet channel 905 has a width of about 250 μτη. In some embodiments, the channel 903 is a diffusion channel. The diffusion channel 903 can include a first outlet channel 908 fluidly coupled to the first outlet 906 and to the second end of the diffusion channel 903. The diffusion channel 903 can further include a second outlet channel 909 fluidly coupled to the second outlet 907 and to the second end of the diffusion channel 903. In some embodiments, at least one of the first outlet channel 908 or the second outlet channel 909 are arranged as curvilinear channels relative to the diffusion channel 903, the first outlet channel 908 configured to receive particles drawn into the first fluid from the second fluid, and the second outlet channel 909 configured to receive the second fluid. In some embodiments, the at least one of the first outlet channel 908 or the second inlet channel 909 has a width of from about 1 nm to about 1 mm. In some embodiments, at least one of first outlet channel 908 or the second outlet channel 909 has a width of about 250 urn. System A system 1000 for separating and detecting particles is disclosed herein. FIG. 10A depicts an illustrative and non-limiting embodiment of the system 1000 to separate and detect particles. As shown in FIG. 10A, in some embodiments, the system 1000 to separate particles from a second fluid (Fluid # 2) into a first fluid (Fluid #1) includes a pump 1008, a valve 1009, a controller 1013, a separation device 1015, and a detector 1012. In some embodiments, the device 1015 includes a first inlet 1001 configured to receive the first fluid (Fluid #1), and a second inlet 1002 configured to receive the second fluid (Fluid # 2), the second fluid (Fluid # 2) having particles of a substance suspended therein. In some embodiments, the device 1015 includes a channel 1003, the channel 1003 including one or more loops formed as a spiral. In some embodiments, the channel 1003 includes a first end and a second end, the first end closer to an outer point of the spiral relative to the second end. In some embodiments, the channel 1003 can be fluidly coupled to the first inlet 1001 and to the second inlet 1002 at the first end. In some embodiments, the channel 1003 can be configured to receive the first fluid from the first inlet 1001 and the second fluid from the second inlet 1002. In some embodiments, the channel 1003 can further be configured to draw at least a portion of the suspended particles from the second fluid into the first fluid based a characteristic of the suspended particles. In some embodiments, the device 1003 includes a first outlet 1006 fluidly can be coupled to the second end of the channel 1003, the first outlet 1006 configured to receive the first fluid (Fluid #1) including the portion of the drawn particles. In some embodiments, a second outlet 1007 fluidly can be coupled to the second end of the channel 1003, the second outlet 1007 configured to receive the second fluid (Fluid #2).

In some embodiments, the system 1000 includes a pump 1008. In some embodiments, the pump 1008 is fluidly coupled to a first source 1010 of the first fluid (Fluid #1) and to a second source 1011 of the second fluid (Fluid #2). In some embodiments, the pump 1008 can be further fluidly coupled to the first inlet 1001 of the device 1003 and to the second inlet 1002 of the device 1003. In some embodiments, the pump 1008 can be configured to pull the first fluid from the first source 1010 and the second fluid from the second source 1011. In some embodiments, the pump 1008 can be further configured to provide the first fluid to the first inlet 1001 and the second fluid to the second inlet 1002 of the device 1003.

In some embodiments, the system 1000 further includes a valve 1009 fluidly coupled to the pump 1008, In some embodiments, the valve 1009 is configured to, in a first setting, permit fluid flow from the first source 1010 of the first fluid (Fluid #1) and from the second source 1011 of the second fluid (Fluid #2) (see FIG. 7A). In some embodiments, the valve 1009 can be further configured to, in a second setting, permit fluid flow from the pump to the first inlet and to the second inlet of the device 1015 (see FIG. 7B). in some embodiments, the valve is a switching valve. In some embodiments, the switching valve is a two-way, six-port switching valve. In some embodiments, a system to separate and detect particles includes a detector 1012. in some embodiments the detector 1012 is associated with the first fluid, which includes separated particles. For example, in one embodiment, the detector 1012 can be fluidly coupled to the first outlet 1006 of the device, the detector 1012 configured to detect particles drawn into the first fluid from the second fluid. In some embodiments, the detector 1012 is configured for detection of at least one characteristic of the particle to be sorted. For example, in one embodiments, the detector is configured to detect molecular mass. In some embodiments, the detector 1012 is a mass spectrometer. In some embodiments, the channel 1003 is formed as a logarithmic spiral with polar coordinates (r, Θ) and a logarithmic curve (r ) of the logarithmic spiral 1003 defined as: r = ae^be In some embodiments, the first inlet 1001 includes a first inlet port configured to fluidly couple the pump 1008 and the valve 1009. In some embodiments, the second inlet 1002 includes a second inlet port configured to fluidly couple the pump 1008 and the valve 1009. In some embodiments, the first outlet 1006 includes a first outlet port, the second outlet 1007 includes a second outlet port. In some embodiments, at least one of the first outlet port or the second outlet port can be configured to fluidly couple a detector 1012 for particles. In some embodiments, the first outlet port is configured to fluidly couple a detector 1012 to detect particles drawn into the first fluid form the second fluid. In some embodiments, the system 1000 further includes a detector fluidly coupled to the first outlet of the device 1015. The is detector configured to detect particles drawn into the first fluid from the second fluid from the second fluid, which drawn particles exit the device 1015 at the first outlet 1006, In some embodiments, the system 1000 further includes a first syringe and a second syringe operably coupled to the pump 1008, described herein with reference to the first syringe 702 and the second syringe 704 of 7A. In some embodiments, the first syringe 702 is configured to receive the first fluid pulled from the pump 700 (see FIG. 7A). In some embodiments, the second syringe 704 is configured to receive the second fluid pulled from the pump 700 (see FIG. 7B). In further embodiments, the first syringe 702 can be farther configured to provide the first fluid to the first inlet 707, such as the first inlet 1001 in FIG. 10B, In some embodiments, the second syringe 704 can be further configured to provide the second fluid to the second inlet 708. In some embodiments, the system 1000, further includes a controller 1013 operatively coupled to the pump 1008 and the valve 1009. In some embodiments, the controller 1013 is configured to switch the valve 1009 to the first setting, e.g., the valve 701 illustrated in FIG. 7A. In the first valve setting, the controller 1013 further configured to direct the pump 1008 to pull at least one of the first fluid (Fluid #1) from the first source 1010 or the second fluid (Fluid #2) from the second source 101 1. In some embodiments, the controller 1013 further configured to switch the valve 1009 to the second setting, e.g., the valve 701 illustrated in FIG. 7B. In in the second valve setting, the controller 1013 further configured to direct the pump 1008 to provide at least one of the first fluid (Fluid #1) to the first inlet 1001 of the device 1015 or the second fluid (Fluid #2) to the second inlet 1002 of the device 1015. In some embodiments, as illustrated in FIG. 10B, the pump 1008' is further fluidly coupled to a third source 1016' of the third fluid. The pump 1009' further configured to pull the third fluid from the third source 1016'. In some embodiments, the second syringe, e.g., the second syringe 704 of FIGS. 7A-7B, can be further configured to receive the third fluid pulled from the pump 1008'. The pump 1008' and the second syringe 704 can be further configured to provide at least one of the second fluid or the third fluid to the second inlet 1002'. In some embodiments, the system 1001 ' can further include a mixing structure 1004' fluidly coupled to the pump 1008'. In some embodiments, the mixing structure 1 004 can be further fluidly coupled to the second source 101 1 ' and the third source 1016'. In some embodiments, the mixing structure can be configured to substantially mix the second fluid and the third fluid. In some embodiments, in the mixing structure is a y-valve. For example, in some embodiments, the third fluid can be used to liberate particles suspended in the second fluid into the combination of the second fluid and third fluid. For example, substantial mixing of the second fluid (e.g. cell suspension) with the third fluid (e.g. cell lysis solution), can liberate particles (e.g. cellular metabolites) into the mixed second fluid and third fluid. The liberated particles can then be separated into the first fluid and subsequently detected. In some embodiments, the system 1000', further includes a controller 1013' operatively coupled to the pump 1008' and the valve 1009'. In some embodiments, the controller 1013' is configured to switch the valve 1009' to the first setting (e.g., such the valve 701 illustrated in FIG, 7A). In the first valve setting, the controller 1013' can be further configured to direct the pump 1008' to pull at least one of the first fluid (Fluid #1) from the first source 1010', the second fluid (Fluid #1) from the second source 1011 ', or the third fluid (Fluid #3) from the third source 1016'. In some embodiments, the controller 1013' further configured to switch the valve to the second setting, e.g., the valve 701 illustrated in FIG. 7B. In the second valve setting, the controller 1013' further configured to direct the pump 1008' to provide at least one of the first fluid (Fluid #1) to the first inlet 1010' of the device 1015', the second fluid (Fluid #2) to the second inlet 1011 ' of the device 1015', or the third fluid (Fluid #3) to the second inlet 101 1 ' of the device 1015'. Methods to separate and/or detect particles FIG. 12 illustrates a method 1200 to separate particles. In some embodiments, the method 1200 can be performed by a separation system such as the system 1000, and can be enabled by a controller, such as the controller 1013, executing computer-executable instructions for executing the method of 1200. At 1201, a first fluid and a second fluid are received in a channel of a device in laminar flow such that turbulent mixing of the first fluid and the second fluid does not occur, the second fluid containing particles of a substance suspended therein, as described herein with reference to the channel 1003 of the device 1015 of FIG. 10A. Laminar flow occurs when a fluid flows in paral lel layers without mixing of the layers. Flowing the first fluid and the second fluid in laminar flow prevents substantial mixing of the first fluid and the second fluid. Restricting turbulent mixing of the first fluid and the second fluid prevents substantial mixing of the suspended particles suspended with the first fluid until acted on by spiral inertial forces during use of the device 1015. In some embodiments, the particles suspended in the second fluid are organic particles, inorganic particles, hybrid particles, one or more cells (eukaryotic or prokaryotic), cellular metabolites, genes and/or gene products. At 1202, at least a portion of particles suspended in the second fluid are drawn from the second fluid into the first fluid based a characteristic of the suspended particles, as illustrated in FIGS. 9B and 9C. In some embodiments, the characteristic of the suspended particles includes a physical property of the suspended particles. In some embodiments, the physical property is diameter or molecular mass. In further embodiments, the physical property is molecular mass. At 1203, the first fluid is separated from the second fluid, the first fluid including the portion of drawn particles. Referring again to FIG. I OA, the device 1015 can be configured such that the first fluid and the second fluid can exit the device 1015 at independent outlets, 1006 and 1007, respectively. For example, in some embodiments, the first fluid containing the portion of drawn particles can be received at the first outlet 1006, and the second fluid can be received at the second outlet 1007. In some embodiments, the receiving at 1202 can further include receiving the first fluid and the second fluid in a spiral channel, described herein with reference to the spiral channel 1003 of FIG. 10A. In some embodiments, the channels is formed as a logarithmic spiral with polar coordinates (r, Θ) and a logarithmic curve (r ) of the logarithmic spiral is defined as: r = e^w

In some embodiments, the receiving at 1202 can further includes receiving the first fluid and the second fluid at flow rates characterized by Reynolds numbers less than about 1 for the first fluid and the second fluid. In some embodiments, the receiving at 1012 can further include receiving the first fluid and the second fluid a flow rate of 50μΙ,/τηίη. For example, in some embodiments, Reynolds numbers less than about 1 prevents turbulent mixing of the fluids flowing through the device during use, and, in some embodiments, this can be achieved at a flow rate of 50 ,L/min. In some embodiments, the first fluid can be received at a flow rate that is different from the second fluid as long as flow rate of the first fluid and the flow rate of the second fluid are characterized by Reynolds numbers less than about 1 . Fluid flow characterized by Reynolds numbers less than about 1 allows for particles below a threshold mass to diffuse away from a second fluid into a first fluid, where the first fluid and the second fluid can be of a different composition and viscosity, without turbulent mixing of the first fluid and the second fluid. In some embodiments, particle separation is modulated by adjusting the fluid flow rate. For example, diffusion of particles from the second fluid into the first fluid can be controlled by adjusting the flow rate through the system, where slower flow rates allow greater diffusion of particles from the second fluid into the first fluid. In some embodiments, the abundance of particles detected can be modulated by adjusting droplet size. One skilled in the art will recognize that these parameters can be adjusted to modify the size/amount of particles that can be drawn from the second fluid into the first fluid. In some embodiments, the speed, volume, and periodicity of injections can be adjusted using the pump and the valve system. In some embodiments, the drawing at 1202 can further include drawing, via spiral iiiertial forces acting on suspended particles during use, at least a portion of the particles suspended in the second fluid from the second fluid into the first fluid based on the characteristic of the suspended particles. In some embodiments, the drawing of the separated particles from the second fluid into the first fluid is based on a physical property of the suspended particles. In some embodiments, the physical property is diameter or molecular mass. In further embodiments, the physical property is molecular mass. In some embodiments, the particles suspended in the second fluid include particles of a plurality of masses. In some embodiments, the drawing at 1202 can further include drawing at least a portion of particles less than a first mass from the second fluid into the first fluid. In some embodiments, the first mass is about 700 Daltons. Referring to FIG. 9B, an illustrati ve embodiment of a first end of a device 900 is depicted where a second fluid containing particles of a plurality of masses is shown entering the channel 903 at a second inlet 905, the second inlet 905 located near the first end of the channel 903. initially, particles suspended in the second fluid are located at a position near the inner wall 910 of the channel 903. Now referring to FIG. 9C, an illustrative embodiment of a second end of a particle separation in a spiral separation device is schematically depicted wherein at least a potion of particles have been drawn into the first fluid from the second fluid. While traversing the spiral 903 channel during use, spiral mertial forces described herein act on particles greater than the first mass to focus those particles to an equilibrium position near the inner wall 910 of the channel 903. Spiral mertial forces further act on particles less than a first mass to focus these particle to an equilibrium position near the outer wall 911 of the channel 903. For example. particles smaller than a first mass can include cellular metabolites liberated from ceils, and particles larger than a first mass can include ceil Iysat.es, proteins, and/or the like. In some embodiments, the method 1200 can further include detecting a signal transmitted by particles suspended in the first fluid or the second fluid. In some embodiments, the detecting can further include processing the detected signal to detect at least one of the presence or amount of the particles suspended in the first fluid or the second fluid, in some embodiments, the detecting can further include detecting, by a detector fluidly coupled to at least one of the first outlet or the second outlet, the signal transmitted by a particle suspended in the first fluid or a particle suspended in the second fluid, wherein first fluid is received at the first outlet and wherein second fluid is received at the second outlet. In some embodiments, the detecting can further include detecting, by a detector fluidly coupled to the first outlet, the signal transmitted particles drawn into the first fluid from the second fluid, wherein the drawn particles are received at the first outlet (e.g., such as the detector 1012 of FIG. 10A). In some embodiments, the first fluid is a solvent compatible with a detector. In some embodiments, the detector is a mass spectrometer. For example, in a non- limiting embodiment, a mass spectrometer can include electrospray ionization, time of flight mass spectrometer (ESI-ToF-MS). One skilled in the art will recognize that a variety mass spectrometers with a variety of ionization sources can be used with the systems and methods described herein. An illustrative embodiment of a solvent compatible with a mass spectrometer (e.g., ESI-ToF) includes 1 % formic acid in water. One skilled in the art will recognize that different solvents can be used with the systems and methods described herein depending on the sample, the detector, and/or the like. In some embodiments, the detector is a biosensor. For example, in non-limiting embodiments, a biosensor can include any of the biosensors described in Nature Biotech. 10 Sep. 2012;30:843; glycose biosensors described in Yoo, E-H., and Lee, 8- Y., Sensor (Basel.) 4 May 2010; 10(5):45558-4576; fluorescent biosensors described in Zhang, C, et. al., 25 Sep 2013;8(11): 1280-1291 , and/or the like, and/or combinations thereof. In some embodiments, the method 1200 can further include providing at least one of the first fluid or the second fluid to the channel of the device (e.g., such as the channel 1003 of the device 1015 of FIG. 10A) . In some embodiments, the providing further includes providing at least one of the first fluid and the second fluid to the channel of the device at a flow rate such that laminar flow of the first fluid and the second fluid is achieved. In some embodiments, the flow rate is about 50 μί,/ηήη. In some embodiments, as described herein with reference to 10A, the providing can further include providing by a pump 1008 fluidly coupled to the channel 1003 of the device 1015, at least one of the first fluid or the second fluid to the channel 1003 of the device 1015, wherein the first fluid is provided to a first inlet 1001 of the channel 1003 and the second fluid is provided to a second inlet 1002 of the channel 1003. In further embodiment, the pump 1008 is fluidly coupled to the first inlet 1001 and the second inlet 1002 of the channel 1003, the first inlet 1001 and the second inlet 1002 are fluidly coupled to the channel 1003. In some embodiments, as described herein with reference to FIG. 10A, the method further includes pulling, by the pump 1008 that is further fluidly coupled to at least one of a first source 1010 of the first fluid or a second source 101 1 of the second fluid, at least one of the first fluid, from the first source 1010 or the second fluid, from the second source 1.01 1 , wherein the first fluid pulled from the first source 1010 is provided to the first inlet 1001 and the second fluid pulled from the second source 101 1 is provided to the second inlet .1002. In some embodiments, the first fluid pulled by the pump 1008 can be received by a first syringe (e.g., such as the first syringe 702 of FIGS. 7A and 7B) operably coupled to the pump 1008 before being provided to the first inlet 1001. In some embodiments, the second fluid pulled by the pump 1008 can be received by a second syringe (e.g., such as the second syringe 704 of FIGS. 7A and 7B) operably coupled to the pump 1008 before being provided to the second inlet 1002. In some embodiments, the method 1200, as described herein with reference to FIG. 10A, includes directing the pump 1008 to pull at least one of the first fluid form the first source 1010 or the second fluid from the second source 101 1 . In some embodiments, the directing further includes directing the pump 1008 to provide at least one of the first fluid to the first inlet 1001 or the second fluid to the second inlet 1002. In some embodiments, the directing is accomplished using a controller 1013 operatively coupled to the pump 1008. In some embodiments, the method 1200, as described herein with reference to FIG. 10A can further include pemiitting, by a valve 1009 operably coupled to the pump 1008, fluid flow from at least one of the first fluid (Fluid #1) from the first source 1010 to the device 1015 or the second fluid. (Fluid #2) from the second source 101 1 to the device 1015. in some embodiment, the valve 1009, in a first setting, permits fluid flow from the first source 1010 and from the second source 10.1 1 to the pump. In some embodiments, the valve 1009 further, in a second setting, permits fluid flow from the pump 1008 to the first inlet 1001 of the device 1015 and to the second inlet 1002 of the device 1015, wherein the first fluid (Fluid #1) is provided to the first inlet 1001 of the device 1015 and the second fluid (Fluid #2) is provided to the second inlet 1002 of the device 1015. In some embodiments, the permitting can further include directing, by a controller .1013 operative!}' coupled to the valve 1009, the valve .1009 to switch between the first setting and the second setting. In some embodiments of the method 1200, the second fluid can be combined with a third fluid. For example, to liberate particles contained in the second fluid (e.g. intracellular metabolites in a cell suspension), a third fluid (e.g. cell lysis solution) can be used, and the liberated particles can be separated into the first fluid using the device, system, and/or method described herein. In some embodiments, the method 1200, as described herein with reference to FIG. lOB, can include providing, by the pump 1008' fluidly coupled to the channel 1003' of the device .1015', at least one of the first fluid (Fluid #1 ), the second fluid (Fluid #2), or the third fluid (Fluid #3) to the channel 1003' of the device 1015', wherein the second fluid (Fluid #2) and the third fluid (Fluid #3) are combined, and wherein the combined second fluid (Fluid #2) and third fluid (Fluid #3) are provided to the second inlet 1002' of the channel 1003'. In some embodiments, the method can further include pulling, by the pump 1008' fluidly coupled to a third source 1016' of the third fluid (Fluid #3), the third fluid (Fluid #3) from the third source .1016'. In some embodiments, the second syringe, e.g., such as the second syringe 702 of FIGS. 7A and 7B, operably coupled to the pump 700 can further receive the second fluid and the third fluid prior to providing the combined second fluid and third fluid to the second inlet 708. In some embodiments, the method 1200, as described herein with reference to FIG. 10B, can further include directing the pump 1008' to pull/draw at least one of the first fluid (Fluid #1) from the first source 1010', the second fluid (Fluid #2) from the second source 1011 ', or the third fluid (Fluid #3) from the third source 10.16'. In some embodiments, the directing can further include directing the pump 1008' to provide at least one of the first fluid (Fluid #1) to the first inlet 100Γ of the device 10.15' or the combined second fluid (Fluid #2) and the third fluid (Fluid #3) to the second inlet 1002' of the device 1015'. In some embodiments, the directing can further include directing by a controller 1013' operably coupled to the pump 1008', In some embodiments, the method 1200, as described herein with reference to FIG. 10B, can further include permitting by a valve 1009' operably coupled to the pump 1008', fluid flow from at least one of the first fluid (Fluid #1 ) from the first source 1010' to the device 1015', the second fluid (Fluid #2) from the second source (1011 ') to the device 1015', or the third fluid (Fluid #3) from the third source 1016' to the device 1015', In some embodiments, the valve 1009', in a first setting, permits fluid flow from the first source 1010', the second source 101 1 ', and the third source 1016'to the pump 1009' (see also FIG. 7A). In some embodiments, the valve 1009' further, in a second setting, permits fluid flow from the pump 1008' to the first inlet 1001 ' and to the second inlet 1002' of the device 1015', wherein the first fluid (Fluid #1) flows to the first inlet 1001 ' of the device 1015', and combined second fluid (Fluid #2) and third fluid (Fluid #3) flows to the second inlet 1002' of the device 1015 ' (see also FIG. 7B). In some embodiments, the permitting of the valve 1009' can further include directing, by the controller 1013' operatively coupled to the valve 1009', wherein the controller 1013' directs the valve 1009' to switch between the first setting and the second setting. In some embodiments, the method 1200 can further includes mixing the second fluid with the third fluid, wherein the second fluid and the third fluid are substantially mixed. In some embodiments, the mixing is accomplished using a mixing structure, e.g., the mixing structure 1004 of FI G. 10B. In some embodiments, the mixing structure 1004 can be fluidly coupled to the second source 101 1 ' of the second fluid (Fluid #2) and the third source 1016' of the third fluid (Fluid 3#), the mixing structure 1004 further fluidly coupled to the pump 1008' and the valve 1009', wherein the mixing structure 1004 substantially mixes the second fluid (Fluid #2) with the third fluid (Fluid 3#). For example, the mixing structure 1004 ca substantially mix the second fluid (e.g., cell suspension) with the third fluid (e.g., cell lysis solution) such that the cells contained in the cell suspension are substantially lysed, In some embodiments of the method 1200, the providing can further include providing, by the pump, isocratic fluid flo through the device during use, described herein with reference to pump 1008' and the device 1015' of FIGS, I OA and 10B. In some embodiments, the providing further includes, providing by the pump 1008', periodic injections of a sample into the device 1015'. In some embodiments, periodic injections of sample prevents fouling of the detector from buildup of large particles, e.g. cell lysates, on the detector. In some embodiments, operation parameters of the pump 1008' and the valve 1009' are set according to instructions programmed into the pump 1008' and valve 1009'. For example, in some embodiments, sample injection time, volume, and flow rate can be controlled by instructions programmed into the pump and valve system. For example, in some embodiments, diffusion of particles can be controlled by adjusting the flow rate through the device wherein slower flow rates allow for greater diffusion. For example, at the flow rate of about 50 μί/πΰη, particles with a mass of about 700 Da. or less display rates of diffusion that allow for sufficient accumulation in the first fluid. In some embodiments, computer software can be designed to operate the system at specified parameters. For example, in some embodiments, computer software can be designed to direct a robot arm to take samples at specified time intervals to monitor changes in a sample over time, In some embodiments of the method 1200, the particles drawn from the second fluid into the first fluid are cellular metabolites. In some embodiments, the second fluid is a biological fluid. In some embodiments, the biological fluid is derived from an organism. In some embodiments, the biological fluid is whole blood. In some embodiments, the biological fluid is urine. In some embodiments, the biological fluid includes cells suspended therein. In some embodiments, the second fluid includes particles suspended in a solvent. In some embodiments, the third fluid is a lysing solution. In some embodiments, the second fluid is a cell suspension and the third fluid is a lysis solution, and the mixing structure substantially mixes the second fluid and the third fluid such that cellular metabolites are liberated from the cells into the mixed second fluid and third fluid. In some embodiments, the cells from which the cellular metabolites are liberated are prokaryotic cells. In some embodiments, the prokaryotic cells are bacterial cells. In some embodiments, the cells from which metabolites are liberated are eukaryotic cells. In some embodiments, the eukaryotic cells are mammalian cells. In some embodiments, the mammalian cells are red blood cells. EXAMPLES Example 1 Data Analysis Upon detection of particles, a detector generates binary pulses (0 or 1) corresponding to detected particles, and a digital representation of the information can be obtained using a signal recognition algorithm. In some embodiments, the detector is a mass spectrometer. For example, in one embodiment, manually selected data can be extracted using pymzML, a Python library for high-throughput bioinformati.es on mass spectrometry data. For example, periodic injection of sample into the device at approximately 5 min intervals can produce mass spectrometry pulses approximately 2 min in length. The intensity of each m/z can be summed for the duration of the pulse and placed into a list for analysis. Customized script written in pymzML is located below: # ! in sr/bin/eiiv python3.2

"""

Demonstration of the extraction of a specific ion chrornatogram, i.e. XIC or EIC

Example:

»> import pymzml, get_exampie_file

»> example file = get example file. open example('small.pwiz. l .l .mzML')

»> run = pymzml.run.Reader(exampie__tile, MSl_Precision = 20e-6, MSnJPreeision = 20e- 6)

»> timeDependentlntensities = []

»> for spectrum in run:

... if spectrum['ms level'] ^::::::: 1 :

... matchList = spectrum.hasPeak(MASS_2_FOLLOW)

... if matchList != []:

... for mzi in matchList:

... timeDependentlntensities. append( [ spectrumf'scan time'], I , mz

])

»> for rt, i, mz in timeDependentlntensities:

... print(^,{0:5.3f}\til : 13.4f}\t {2: 10}'.format( t, i, mz )) from future import print_function

import sys

import pymzml

import get_example_file

masses ^:::: []

MASS 2 FOLLOW1 = 70.0643

VIASS 2 FOLLO : = 72.0800

MASS 2 FOLLOWS = 80.9470

MASSJTFOLLOW5 = 84.0441

MASS_2 _FOLLOW6 = 86.0957

MASS 2 FOLLOW7 = 87.0991

MASS 2 FOLLOWS = 87.2289

MASS 2 FOLLOWS = 88.1089

MASS^~Y FOLLQW1G = 90.9762

MASS 2 FOLLOW! 1 = 93.0697 MASS z. F0LL0W12 96.9207

MASS ^~2 ^"FOLLOW! 3 101 .0602

MASS^" 2 FOLLOW14 102.06

MASS 7 FOLLOW! 5 1 03.053

MASS^" 7 FOLLOW 16 105.0697

MASS^" FOLLOW! 7 107.0495

MASS ¥ ^"FOLLOW! 8 1 10.0709

MASS^" FOLLOW19 1 15.0869

MASS 2 FOLLOW20 1 16.0690

MASS 7 ^"FOLLOW21 1 17.0738

MASS^" FOLLOW^R22 1 18.0848

MASS ^~2 ^"FOLLOW23 1 19.0891

MASS^" FOLLOW24 120.0788

MASS 2 ^"FOLLOW25 121.0649

MASS 7 FOLLOW26 132.0998

MASS^" ^"FOLLOW27 133.0294

MASS FOLLOW28 133.1028

MASS ^~2 ^"FOLLOW29 140.0656

MASS^" 2 FOLLOW30 141.9560

MASS 7 FOLLOW31 147.1 102

MASS^" 7 FQLLQW32 148.0578

MASS^" FOLLOW33 150.0560

MASS ^~2 ^"FOLLOW34 152.0294

MASS^" A ^"FOLLOWS 5 154.0811MASS 2 FOLLOW36 = 156.0742

MASS 2 FOLLOW37 166.0834

MASS 7 FOLLOW38 1 67.0884

MASS^" FOLLOW^R39 175.1 164

MASS FOLLOW40 176.0623

MASS ^~2 ^"FOLLOW41 188.0659

MASS^" 2 ^"FOLLOW42 191.0735

MASS 7 ^"FOLLOW43 205.0932

MASS^" 7 ^"FOLLOW44 210.0467

MASS^" FOLLOW45 215.1355

MASS ^~2 ^"FOLLOW46 229.151 !

MASS^" A FOLLOW47 231.1667

MASS 2 FOLLOW48 235.1 145

MASS 7 ^"FOLLOW49 254.1567

MASS^" FOLLOW^R50 268.1012

MASS ^~2 FOLLOWS ! 288.1872

MASS^" A FOLLOWS 2 288.6744

MASS 2 ^"FOLLOW53 292.1913

MASS 7 FOLLOW54 293.9735

MASS^" ^"FOLLOW55 302.1603

MASS FOLLOW56 328.2170

MASS ^~2 ^"FOLLOWS 7 337.6893

MASS^" ^"2 ^"FOLLOWS 8 342.2330 MASS_2_FOLLOW59 = 349.9354

MASS 2 FOLLOW60 - 360.1928

MASS^~2^~FOLLOW61 = 385.2370

MASS_2_FOLLOW62 = 407.2222

MASS 2 FOLLOW63 - 411.0256

MASS_2_FOLLOW64 = 417.21

MASS_2_FOLLOW65 ==^: 439.2875

MASS 2 FOLLOW66 = 461.2793

MASS_2_FOLLOW67 = 491.2807

MASS 2 FOLLOW68 = 524.2706

MASS 2 FOLLOW69 = 530.291

MASS^~2^~FOLLOW70 ==^: 552.2757

MASS 2 FOLLOW71 - 553.3277

MASS 2^~FOLLOW72 = 562.2855

MASS_2_FOLLOW73 = 576.3443

MASS 2 FOLLOW74 = 577.3461

MASS^~2^~FOLLOW75 = 598.3251

MASS 2 FOLLOW76 - 604.2926

MASS 2 FOLLOW77 = 652.3955

MASS_2_FOLLOW78 = 659.3327

MASS 2 _FOLLOW79 674,3772

masses.append(MASS_2_FOLLOW 1)

masses.append(MASS_2_FOLLOW2)

niasses.append(MASS 2 FOLLOW3)

#masses.append(MASS_2_FOLLOW4)

masses.append(MASS 2 FOLLOWS)

masses.append(MASS]]2^~FOLLOW6)

masses.append(MASS_2_FOLLOW7)

masses.appendiMASS 2 FOLLOWS)

masses.append(MASS^~2^~FOLLOW9)

masses.append(M ASS^~2^~FOLLO W ! 0)

masses,append(M ASS 2 FOLLOW 11 )

masses.append(MASS 2^~FOLLOW 12)

masses.append(MASS_2_FOLLOW 13)

masses.append(MASS 2 FOLLOW 14)

masses.append(MASS^~2^~FOLLO W 15)

masses.append( ASS 2 FOLLOW 16)

masses.appendiMASS ^"Y FOLLOW 17)

masses.appendi ASSY ^"FOLLOW 18)

masses.appendi MA SS 2 FOLLOW 1 9}

masses.append(MASS^~2^~FOLLOW20)

masses.append(M ASS_2_FOLLOW2.1 )masses.append(MASS_2_FOLLOW22) masses.append(MASS 2 FOLLOW^T23)

masses.append(MASS 2^~FOLLOW24)

masses.appendiMASS 2 FOLLOW25)

masses.append(MASS^~2^~FOLLOW26) masses.append(MASS_2_FQLLOW27) masses.appendi MA SS 2 FOLLOW28) masses.append(MASS 2 FOLLOW29) raasses.append( ASS_2_FOLLOW30) masses.append(MASS 2 FOLLOWS 1) masses.append(MASS 2^~FOLLOW32) masses.append(MASS_2_FOLLOW33) masses.append(MASS 2 FOLLOW34) masses.append(MASSl2 FOLLOW35) masses.append(MASS _2_.. FOLLOW36) masses, append(MASS 2 FOLLOWS 7) masses.append(MASS 2^~FOLLOW38) masses.append( ASS 2 FOLLOW39) masses.appendi MASS 2 FO! . i .OW40) masses.append(M ASS_2_FOLLO W41 ) masses. append(M ASS 2 FOLLOW42) masses.append(MASS 2^~FOLLOW43) masses.appendi MA SS 2 FOLLOW44) masses.append(MASS^~2^~FOLLOW45) masses.append(MASS^~2^~FOLLOW46) masses.append(MASS 2 FOLLOW47) masses.appendi MASS 2 OLLOW48) masses.appendi MASS_2_FOLLOW49) masses.append(MASS 2 FOLLOW50) masses.append(MASS^~2 OLLO W51 ) rnasses,apperid(MASS 2 FQLLOW52) masses. append(MASS 2 FOLLOW^T53) masses.appendi MASS 2 OLLOW54) masses.append(MASS 2 FOLLOW55) masses.append(MASS 2 FOLLOW56) masses.append(M ASS^~2 ^~FOLLO W57) masses.append( ASS 2 FOLLOW58) masses.append(MASS 2^~FOLLOW59) masses.appendi ^'MASS_2_FOLLOW60) masses.append(MASS 2 FOLLOW61) masses.append(MASS^~2^~FOLLOW62) masses.append(MASS 2 FOLLOW^r63) masses.append(MASS^~2 .FOLLOW64) masses.append(MASS 2^~FOLLOW65) masses.appendi MA SS 2 FOLLOW66) masses.append(MASSl2 OLLOW67) masses.append(MASS_2_FOLLOW68) masses.append(MASS 2 FOLLOW69) masses.appendi MASSl2 OLLOW70) masses.appendi MA SS 2 FOU OW7 I } masses.append(MASS _2 FOLLOW72) masses.append(MASS_2_FOLLOW73)

masses.append(MASS 2 FOLLOW74)

masses.append(MASS^~2^~FOLLOW75)

masses.append(MASS_2_FOLLOW76)

masses, append(MASS 2 FOLLOW77)

masses.append(MASS_2^~FOLLOW78)

masses.append(MASS_2_FOLLOW79)

total intensity = {}

intensity = 1.0

run ===^: pymzmi.run.Reader('20131 116 1100 Start _eco3.il l .mzML', MSI Precision ===^: 20e-6, MSn Precision = 20e-6)

for spectrum in run:

#print(spectrura)

#print(spectrum['scan time']) if spectrum.has_key('scan time'):

rt = spectrum['scan time']

if (rt < 16.6) or (rt > 21.6):

continue

for mass in masses:

key = mass

if (not key in total_intensity):

total in tensity [key] ^:::: .1.0

peaks = spectrum.hasPeak(mass)

if(len(peaks) == 0):

continue

for mz, I in peaks:

total in tensity [key] I total sort ^::: sorted(total intensity)

for each in total sort:

print(total__intensity[each])

By coupling the device to a mass spectrometer, untargeted metabolomics profiles can be obtained that depict phenotypic information form the quantification of numerous molecular features that may change in response to perturbations. Each periodic injection generates a binary pulse (0 or 1 ) that produces a distinct chromatogram. Feature-based pattern analysis using pattern recognition algorithms transforms the chromatogram into an abimdance profiles, allowing for identification of reproducible biological information that can be used to predictively interpret the relationship between abundance patterns and phenotypes. Abundance profiles at distinct time points can be compared to observe changes occurring over time. These profiles can create forecastable metabolic trajectories that can be used for point-of-eare diagnoses. A device. system, and/or method disclosed herein dramatically increases temporal resolution by removing large molecules prior to detection, and allow for the detection of oscillating metabolic transient states in response to stimuli. Example 2 Fabrication of particle §eparatios¾ structure To illustrate the use of spiral inertial forces as defined herein to separate particles in spiral fluidic channels, a device was fabricated using polydimethyisiloxane (PDMS, Sylgard 184, Dow Corning)., as described herein with reference to the device 900 of FIG. 9A. The channel 903 design includes 5-ioops arranged in a logarithmic spiral geometry in which spacing between successive loops of the spiral channel 903 decreasing in geometric progression by a factor of 0.75 when measured from the outside of the spiral to the inside, and a spacing between the first and the second loop 1 mm. The channel 903 is 500 μτη wide and 10-12 μηι high, with an outer diameter of about 17.78 mm and an inner diameter of about 7.62 mm, A first inlet 901 and a second inlet 902 are fluidly coupled to the first end of the channei 903, the first end closer to the outer point of the spiral. The first inlet 901 and the second inlet 902 are fluidly coupled to the channel 903 by a first inlet channel 904 and a second inlet channel 905, respectively. The first inlet channel 904 and the second inlet channel 905 are of a width of 250 μτη. A first outlet, 906 and a second outlet 907 are fluidly coupled to the second of the channel 903, the second end of the channel closer to the inner point of the spiral. The channel 903 is connected to the first outlet 906 and the second outlet 907 by a first curvilinear outlet channel 908 and a second curvilinear outlet channel 909, respectively, the first outlet channei 908 and the second outlet channel 909 of a width of 250 μηι. Ports of 2.54 mm in diameter are coupled to the first inlet 901, the second inlet 902, the first outlet 906, and the second outlet 907. The device 900 was fabricated using standard rapid prototyping soft lithography methods for microfluidics (Duffy, D.C. et al. Anal, Chem,. 1998, 70, 4974-84). Polycarbonate molds for PDMS were used to create SU8-2010 masters on which the device 900 was fabricated. Master molds were fabricated using a mini-milling machine (Grizzly Industrial, Inc. Model G8689).

To create master molds, 4 mL of SU8-2010 photoresist (Microchem) were patterned on a cleaned 4" silicon wafer using conventional photolithography techniques. Spin coating of SU8- 2010 photoresist (Microchem) on the 4" silicon wafer was performed at 500 rpm for 5-10 sec with an acceleration of 100 rpm/s followed by 3500rpm for 30 seconds with an acceleration of 300 rpm/s. The wafer was soft baked at 95°C on a hot plate for 2-3 minutes. The coated wafer was exposed to a long pass filter and photomask at 120m.f/cm³ for 5-15 s, SU-8 developer (Microchem) solution was added for 2-3 min. Then, the coated wafer was sprayed with developer for 10 s followed by 10 s of ^!PrOH. The wafer was then hard baked at 150°C for 10-20 min, and immersed in Microchem remover PG for 2-5 min. PDMS prepolymer (Slygard 184, Dow Corning) was mixed with the curing agent at a 10: I ratio and then cast on the SU8-2010 master to replicate features of the device 900. After curing in a vacuum oven for 4 hr at 65°C, the PDMS chip was removed from the SU8-2010 master. Port holes of 2.54 mm width, coupled to the inlets 901 and 902 and to the outlets 907 and 908, were cored in the PDMS-fabricated device 900 using a hole punch and fitted with a modified 18 gauge syringe needle, as shown in FIG. 11B. The device 900 was bonded to a glass substrate about 1 mm th ck using 0₂ plasma (MARCH etcher, Nordson). A pump and a valve system was designed to fluidly couple fluid sources to the device 900, such as the pump 700 and valve 701 of FIGS. 7 A. and 7B. In addition, the pump 700 and the valve 701 was designed to provide fluids to the device at a flow rate, periodicity of sample injection, volume, and the like. FIG. 7A schematically illustrates an embodiment of the pump 700 and the valve 701 fluidly coupled to a source of a first fluid 703, a source of a second fluid 705, and a source of a third fluid 714. FIG, 7B schematically illustrates an embodiment of the pump 700 and the valve 701 system fluidly coupled to the first inlet 707 and a second inlet 708 of the device. For example, a dual syringe pump 700 (NE-4000, New Era Pump Systems Inc.) and a two-way, six-port switching valve 701 (MXP-9900, Rheodyne) was used to interface the fluid sources with the particle separation structure. FIG. 1 IB illustrates fluid coupling of the fluids to the device 1 105 using PEEK™ Tubing 1 101 with 1/32 inch outer diameter and 0.005 mm inner diameter (Upchurch), which was inserted and sealed into the modified 18 gauge syringe needle 1102 using the PDMS as glue. Referring to FIG, 9B, Particles suspended in the second fluid, which is injected into the second outlet 902, are initially located near an inner wall 910 of the spiral channel 903. Referring to FIG. 9C, as the first fluid and the second fluid traverse the device 900, smaller particles (e.g., MW < 700 Da.) are drawn into the first fluid, which is located in a stream near an outer wall 911 of the spiral channel 903. As the fluids approach the second end of the spiral channel 903, at least a portion of smaller particles (e.g., particles less than a first mass, e.g. MW < 700 Da.) are drawn into the first fluid and located in an equilibrium position near the outer wall 911 of the spiral channel 903. The drawn particles are collected at the first outlet 906 at the second end of the spiral channel 903. The second fluid including particles not drawn into the first fluid can be collected at the second outlet 907 at the second end of the spiral channel 903, Particles drawn into the first fluid, which were collected at the first outlet 906, can be detected by a mass spectrometer. FIG. 13 A depicts the total ion count (TIC) for particles drawn into the first fluid form the second fluid during periodic injections at 5 minute intervals over a 30 minute run. FIG. 13B depicts differences in TIC as a function of injection time point. Channel dimensions and flow were optimized to capture sufficient material in the first fluid for analysis, while minimizing buildup on the detector or ionization source during long periods of continuous instrument operation. At a flow rate of 50 μί/πνΐη, small particles (e.g. MW < 700 Da.) displayed rates of diffusion that allowed for significant accumulation in the first fluid.

Diffusive extraction of oxidized glutathione (GSSG). To experimentally evaluate particle separation using the device 900, an oxidized glutathione (GSSG) diffusion experiment was performed by periodically injecting GSSG in acetonitrile and 0.1% formic acid at the second inlet 902 at an isocratic flow of 50 μΐν'ηιηι. GSSG is a midsized metabolite with a molecule weight of 612 Da (m/z 613.159 M+H+). GSSG diffusion experiments were performed on an ion trap (6340; Agilent Technologies), using an isocratic flow (1 100 HPLC; Agilent Technologies) of 50 μΐ,/min (50% A ^:::: 0.1 % formic acid in water, 50% B ^:::: 0.1 % formic acid in acetonitrile) operated in positive electrospray ionization mode. In MS mode, maximum accumulation time was set at 500 ms, with a scan range of 50-2200 m/z and averages set to 3. For multiple reaction monitoring (MRM), masses were selected and isolated for S(n) with a width of 4.0. Periodic injections of GSSG occurred at 5 minute intervals over a 30 minute run. Quantification of diffusion was measured by the abundance of GSSG detected at each of the outlets, FIG. 14A and FIG. 14B graphical!)' illustrate separation of GSSG (613.1 ni/z) in the device versus a GSSG standard, e.g., such as the device 900 of FIG. 9A. FIG. 14A depicts the extracted ion chromatogram (EIC) of separated GSSG (lower curve) during five periodic injections of GSSG into the second inlet 902 of the device 900 versus the EIC of a GSSG standard (higher) injected into the first inlet 901 of the device 900. The device 900 had a measured diffusion efficiency of 23.23 +/- 2.33% for diffusion of GSSG from the second fluid into the first fluid. FIG. 14B shows resolved isotopic peaks of the separated GSSG, indicating that GSSG was drawn into the second fluid from the first fluid. These experiments showed that injection periodicity may be reduced to 3 minutes without significant sample carryover in successive nins. Testing indicated that the diffusion efficiency of 23.23 +/- 2.33% for small particles (e.g. MW < 700 Da.) was sufficient as it ensured that substantially all large particles (e.g. cellular polymers and cell lysis debris) had insufficient time to diffuse into the first fluid, which first fluid is directed to a detector for detection. Example 4 Metabolite monitoring of growing E. coli cell culture To experimentally evaluate the ability of the device 900 to monitor living systems, metabolites produced from a growing culture of E. coli were monitored. Automated sampling directly from the E. coli cell culture on a 5 minute cycle was achieve using a dual syringe pump (NE-4000, New Era Pump Systems Inc.) and a two-way, six-port switching valve (MXP-99G0, Rlieodvne), described herein with reference to the pump 700 and the valve 701 depicted in FIGS. 7A and 7B, where the second syringe 704 is fluidly coupled to the E. coli cell culture 705 and a cell lysis solution 714 (e.g., 0. 1 % formic acid in acetonitrile). E. coli ceil culture growth analyses were performed on an ion trap (6340; Agilent Technologies) using an isocratic flow (1 100 HPLC; Agilent Technologies) of 50 fiL/min (50% A = 0.1 % formic acid in water, 50% B = 0.1 % formic acid in acetonitri le). The system was operated in positive electrospray ionization mode, using an extended dynamic range (50-1700 m/z) at 1 scan per second. Direct injection of 30-592 cells (Optical Density) in an injection volume of 2 μΐ. generated a sufficient signal for analysis without saturating the spiral biomolecuie extraction chip (100) or the mass spectrometer. For multiple reaction monitoring (MRM) of metabolites from E. coli, masses with a width of 4.0 were selected and isolated for MS(n). m/z were manually validated with Masshunter Qua! (Agilent), and the intensities were imported into R, where data visualization was performed using principal component analysis (PCA) or plot, R function prcomp and plot. Data was mean centered using function prcomp or scale to negate the differences in pulse ionization abundance. FIG. 15A graphically illustrates the abundance changes of 77 small molecules that were detected in an E. coli. cell culture growth, where the y-axis represents abundance and the x-axis represents time. Over the monitoring period, these detected metabolites exhibit changes in abundance as a function of time. Referring to Fig. 15B, four representative metabolites showing smooth increases and decreases in abundance over a 6 hour monitoring period are graphically illustrated. Referring now to Fig. ISC, four other representative metabolites exhibiting oscillations in abundance over a 6 hour monitoring period are illustrated. Because each of these metabolites displayed unique abundance changes over time, the abundance changes resulted from metabolic changes, not an instrument artifact, Referring to FIG, 16, the abundance of the 77 small molecules detected consistently in each pulse over 15 sequential time points were visualized using principal component analysis (PCA). Time points are separated in chronological order, and the composition of any given time point, as determined by PCA, is most similar to the composition measured at the previous and the subsequent time points, showing a trajectory during cell culture growth. Thus, changes in metabolite abundance, which can be visualized by multivariate analysis, such as PCA, can be used to monitor cell cultures according to some embodiments disclosed hererin. Example 5 Reproducible monitoring of metabolic changes To experimentally evaluate the ability of the device 900 to detect reproducible metabolic changes over time, replicate E. coli cell cultures were used. ESI-time of flight (ESI-ToF) analyses were performed using an isocratie flow ( 1290 UPLC; Agilent Technologies) of 50 iL/min (50% A = 0.1 % formic acid in water, 50% B = 0.1 % formic acid in acetonitrile) coupled to a quadrupole-ToF (Q-ToF) (6538; Agilent Technologies). The system was operated in positive electrospray ionization mode, using an extended dynamic range (50-1700 m/z) at 1 scan per second. Direct injection of 148-2960 cells (Optical Density) in an injection volume of 10 μΐ. generated a sufficient signal for analysis without saturating the particle separation structure 900 or the mass spectrometer. For multiple reaction monitoring (MRM) of metabolites from E. co!i, masses with a width of 4.0 were selected and isolated for MS(n). m/z were manually validated with Masshunter Qual (Agilent), and the intensities were imported into R, where data visualization was performed using principal component analysis (PCA) or plot, R function prcomp and plot. Data was mean centered using function prcomp or scale to negate the differences in pulse ionization abundance. Replicate cell cultures of the same cells propagated under similar conditions are expected to have similar metabolic fingerprints and substantially reproducible changes over time. To test for similarity in metabolic fingerprints in replicate cultures, data from 3 independent batch cultures of E. coli were analyzed over a period of 8.5 hours, indicated by black, red, and green coloring, respectively, and visualized with a PCA plot. Referring to FIG. 17, the PCA plot shows that there is a substantially distinct conservation in the trajectory of individual plots for replicate I (black) and replicate 2 (red), indicating simi lar metabolic compositions. Example 6 Metabolic response to oxidative stress To experimentally evaluate the ability of the device 900 to detect small changes in the metabolic state of ceils, 100 μΜ H₂0₂ was added to replicate 3 (green) after 4 hours run time. ESI-time of flight (ESI-ToF) analyses were performed using an isocratie flow (1290 UPLC; Agilent Technologies) of 50 μί . rnin (50% A ^::: 0/1 % formic acid in water, 50% B ^::: 0.1 % formic acid in acetonitrile) coupled to a quadrupole-ToF (Q-ToF) (6538; Agilent Technologies). The system was operated in positive electrospray ionization mode, using an extended dynamic range (50-1700 m/z) at 1 scan per second. Direct injection of 148-2960 cells (Optical Density) in an injection volume of 10 μΕ generated a sufficient signal for analysis without saturating the spiral particle separation system or the mass spectrometer. For multiple reaction monitoring (MRM) of metabolites from E. coli, masses with a width of 4.0 were selected and isolated for MS(n). m/z were manually validated with Masshunter Qual (Agilent), and the intensities were imported into R, where data viuSualization was performed using principal component analysis (PCA) or plot, R function prconip and plot. Data was mean centered using function prcomp or scale to negate the differences in pulse ionization abundance. Referring again to FIG. 17, a change in the trajectory of replicate 3 (green) corresponding to oxidative stress was detected. Example 7 Forecastable metabolic trajectories To experimentally evaluate the device 900 to measure forecastable metabolic trajectories in response to perturbations and for biornarker identification, metabolite abundance plots were compared over time before and after perturbation. Using an E. coli cell culture, automated sampling of three replicate growth cultures were performed over a period of 8.5 hours. After 4 hours run time, 100 μΜ ₂0? was added to replicate 3 to observe metabolic changes in response to ox dative stress. ESI-time of flight (ESI-ToF) analyses were performed using an isocratic flow ( 1290 UPLC; Agilent Technologies) of 50 nL/min (50% A = 0/1 % formic acid in water, 50% B = 0.1 % formic acid in acetomtrile) coupled to a quadrupole-ToF (Q-ToF) (6538; Agilent Technologies). The system was operated in positive electrospray ionization mode, using an extended dynamic range (50-1700 m/z) at 1 scan per second. Direct injection of 148-2960 cells (Optical Density) in an injection volume of 10 μΐ. generated a sufficient signal for analysis without saturating the particle separation structure 900 or the mass spectrometer. For multiple reaction monitoring (MRM) of metabolites from E. coli, masses with a width of 4.0 were selected and isolated for MS(n). m/z were manually validated with Masshunter Qual (Agilent), and the intensities were imported into R, where data viuSualization was performed using principal component analysis (PCA) or plot, R function prcomp and plot. Data was mean centered using function prcomp or scale to negate the differences in pulse ionization abundance. Plots in the abundance of 77 diffusively extracted small molecules were compared for the three replicates. Referring to FIG. 18, change in small molecule abundance during E, coli growth for five small molecules in three growth replicates (Y-axis: abundance; X-axis: time) are graphically depicted. Temporal changes in abundance of four small molecules (m/z = 110.0709, 166.0834, 175.1 164, 205.0932) were conserved across the three growth replicates, which explains the similar trajectories presented in FIG. 17. However, a biomarker of oxidative stress was observed in the abundance of one small molecule (132.1001 m/z), which was identified as leucine/isoleucine with MS/MS experiments. The ~· 10 fold decrease in leucine/isoleucine abundance was observed to occur in response to oxidative stress induced by f I ·<>.>. This abundance change agrees with a known biological response to oxidative stress involving leucine supplementation to protect cells. This experiment is illustrative of monitoring amino acid abundance as a biomarker of a physiological condition, Example 8 Analysis of Urine To experimentally evaluate the ability of the device 900 to analyze urine samples for metabolites, urine analysis was performed. ESI-time of flight (ESI-ToF) analyses were performed using an isocratic flow ( 1290 UPLC; Agilent Technologies) of 50 j L/min (50% A = 0/1 % formic acid in water, 50% B = 0.1 % formic acid in acetonitrile) coupled to a quadrupole-ToF (Q-ToF) (6538; Agilent Technologies). The system was operated in positive electrospray ionization mode, using an extended dynamic range (50-1700 m/z) at 1 scan per second. For multiple reaction monitoring (MRM) of metabolites from urine, masses with a width of 4.0 were selected and isolated for MS(n). m/z were manually validated with Masshunter Qua! (Agilent). FIG. 19A depicts the EIC of 40 metabolites detected in urine (Y -axis: ion count; X-axis: time). A least seven measurements were taken from periodic injections of urine into the spiral particle separation structure 900 over a period of thirty minutes, with a time resolution of 5 minutes. Referring to FIG. 19B, the EIC of creatinine detected in the urine sample, which is a biomarker of physiological conditions, is depicted (Y-axis: ion count; X-axis: time). Now referring to FIG. 19C, the EIC of another biomarker of physiological conditions detected in the urine sample, urea, is depicted (Y-axis: ion count; X-axis: time). Example 9 Analysis of Whole Blood To experimentally evaluate the ability of the device 900 to analyze urine samples for metabolites, urine analysis was performed. ESI-time of flight (ESI-ToF) analyses were performed using an isocratic flow (1290 UPLC; Agilent Technologies) of 50 piL/min (50% A = 0/1 % formic acid in water, 50% B = 0.1 % formic acid in acetonitrile) coupled to a quadrupole-ToF (Q-ToF) (6538; Agilent Technologies). The system was operated in positive eleetrospray ionization mode, using an extended dynamic range (50-1700 ni/z) at 1 scan per second. For multiple reaction monitoring (MRM) of metabolites from whole blood, masses with a width of 4.0 were selected and isolated for MS(n). m/z were manually validated with Masshunter Qua! (Agilent). FIG . 20A graphical ly depicts the EIC of 4 metabolites and 1 protein detected in whole blood (Y-axis: ion count; X-axis: time). At least five measurements were taken from periodic injections of whole into the spiral particle separation structure 900 over a period of thirty minutes, with a time resolution of 5 minutes. Referring to FIG. 20B, the EIC of 4 small molecule metabolites detected in whole blood are depicted (Y-axis: ion count; X-axis: time). Now referring to FIG. 20C, the EIC of Hemoglobin detected in whole blood is depicted (Y-axis: ion count; X-axis: time). Some embodiments described herein relate to a computer storage product with a non- transitory computer-readable medium (also can be referred to as a non-transitory processor- readable medium) having instructions or computer code thereon for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not include transitory propagating signals per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or a cable). The media and computer code (also can be referred to as code) may be those designed and constructed for the specific purpose or purposes. Examples of no -transitory computer-readable media include, but are not limited to: magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as Compact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read Only Memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier wave signal processing modules; and hardware devices that are specially configured to store and execute program code, such as Application-Specific Integrated Circuits (ASICs), Programmable Logic Devices (PLDs), Read-Only Memory (ROM) and Random-Access Memory (RAM) devices. Other embodiments described herein relate to a computer program product, which can include, for example, the instructions and/or computer code discussed herein Examples of computer code include, but are not limited to, micro-code or niiero- instructions, machine instructions, byte code, such as produced by a compiler, and/or files containing higher-level instructions that are executed by a computer using an interpreter. For example, embodiments may be implemented using C, Java, C++, MATLAB or other programming languages and/or other development tools. The processors described herein can be any processors (e.g., a central processing unit (CPU), an application-specific integrated circuit (ASIC), and/or a field programmable gate array (FPGA)) configured to execute one or more instructions received from, for example, a memory. In some embodiments, at least one processor can be a Reduced Instruction Set computing (RISC) processor. Each processor can be in communication with a memory and/or a network card. In some embodiments, each processor can accordingly send information (e.g., data, instructions and/or network data packets) to and/or receive information from a memor and/or a network card. The memory can be any memory (e.g., a RAM, a ROM, a hard disk drive, an optical drive, other removable media) configured to store information (e.g., one or more software applications, user account information, media, text, etc.). The memory can include one or more modules performing the functions described herein. In some embodiments, the functions described herein can be performed by any number of modules. For example, in some embodiments, the functions described herein can be performed by a single module. While various embodiments have been described above, it should be understood that they have been presented by way of example, and not limitation. Where methods described above indicate certain events occurring in certain order, the ordering of certain events can be modified, and certain events may not occur. Additionally, certain of the events may be performed concurrently in a parallel process when possible, as wel l as performed sequentially as described above. Unless defined otherwise, all technical and scientific terms herein have the same meaning as comrnoniy understood by one of ordinary skill in the art to which this invention belongs. Although any method and materials, similar or equivalent to those described herein, can be used in the practice or testing of the present invention, the preferred methods and materials are described herein. All publications, patents, and patent publications cited are incorporated by reference herein in their entirety for all purposes. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth and as follows in the scope of the appended claims. All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entireties for ail purposes. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world.

Claims

What is claimed is: 1. A device, comprising: a first inlet configured to receive a first fluid; a second inlet configured to receive a second fluid, the second fluid having particles of a substance suspended therein; a channel including one or more loops formed as a spiral, the channel including a first end and a second end, the first end closer to an outer point of the spiral relative to the second end, the channel tluidly coupled to the first inlet and to the second inlet at the first end, the channel configured to receive the first fluid from the first inlet and the second fluid from the second inlet, the channel further configured to draw at least a portion of the suspended particles from the second fluid into the first fluid based on a characteristic of the suspended particles; a first outlet tluidly coupled to the second end of the channel, the first outlet configured to receive the first fluid including the portion of the drawn particles; and a second outlet fluidiy coupled to the second end of the channel, the second outlet configured to receive the second fluid.

2. The device of claim 1 , wherein at least a portion of the device is fabricated from one or more non-conductive polymeric materials.

3. The device of claim 1 , wherein at least a portion of the device is fabricated from one or more of poly-dimethylsiloxane or thermoplastics.

4. The device of claim 1 , wherein the channel is formed as a logarithmic spiral with polar coordinates (/', Θ) and a logarithmic curve (r) of the logarithmic spiral defined as: r - ae^h0

5. The de vice of claim 1 , the channel includes between I loop to 5 loops.

6. The device of claim 1 , the one or more loops including a plurality of loops, the plurality of loops including a spacing between successive loops, the spacing between successive loops changing in geometric progression by a factor of about 0.75 when measured from outside of the spiral to inside of the spiral.

7. The device of claim 1 , wherein the channel has a width of about 1 nm to about 1 mm.

8. The device of claim 7, wherein the channel has a width of about 500 μχη.

9. The device of claim 1 , wherein the channel has a length such that the portion of the suspended particles are drawn from the second fluid info the first fluid.

10. The device of claim 9, wherein the channel has a length between about 5 cm to about 25 cm.

1 1 . The device of claim 1 , the first inlet including a first inlet port configured to fluidly couple a source of the first fluid, and the second inlet including a second inlet port configured to fluidly couple a source of the second fluid.

12. The device of claim 1 , the first outlet including a first outlet port and the second outlet including a second outlet port.

13. The device of claim 1 , wherein the channel is a diffusion channel, further comprising: a first inlet channel fluidly coupled to the first inlet and to the first end of the diffusion channel; and a second inlet channel fluidly coupled to the second inlet and to the first end of the diffusion channel.

14. The device of claim 13, wherein at least one of the first inlet channel or the second inlet channel has a width of about 1 nm to about 1 mm.

15. The device of claim 14, wherein at least one of the first inlet channel or the second inlet channel has a width of about 250 μηι.

16. The device of claim 1 , wherein the channel is a diffusion channel, further comprising: a first outlet channel fluidly coupled to the first outlet and to the second end of the diffusion channel; and a second outlet channel fluidly coupled to the second outlet and to the second end of the diffusion channel.

17. The device of claim 16, wherein at least one of the first outlet channel or the second outlet channel are arranged as curvilinear channels relative to the diffusion channel, the first curvilinear outlet channel configured to receive particles drawn into the first fluid from the second fluid, and the second curvilinear outlet channel configured to receive the second fluid,

18. The device of claim 17, wherein at least one of the first outlet channel or the second outlet channel has a width of about 1 nm to about 1 mm 19. The device of claim 18, wherein at least one of the first outlet channel or the second outlet channel has a width of about 250 um. 20. The device of claim 1, wherein the characteristic of the suspended particles includes molecular mass. 21. A system for separating and detecting particles comprising: (i) a device comprising: (a) a first inlet configured to receive a first fluid; (b) a second inlet configured to receive a second fluid, the second fluid having particles of a substance suspended therein; (c) a channel including one or more loops formed as a spiral, the channel including a first end and a second end, the first end closer to an outer point of the spiral relative to the second end, the channel fluidly coupled to the first inlet and to the second inlet at the first end, the channel configured to receive the first fluid from the first inlet and the second fluid from the second inlet, the channel further configured to draw at least a portion of the suspended particles from the second fluid into the first fluid based on a characteristic of the suspended particles; (d) a first outlet fluidly coupled to the second end of the channel, the first outlet configured to receive the first fluid including the portion of the drawn particles; and 1 (ε) a. second outlet fluidiy coupled to the second end of the channel, the second

2 outlet configured to receive the second fluid;

3 (ii) a pump fluidiy coupled to a first source of the first fluid and a second source of the

4 second fluid, the pump further fluidiy coupled to the first inlet of the device and to the

5 second inlet of the device, the pump configured to pull the first fluid from the first

6 source and the second fluid from the second source, the pump further configured to

7 provide the first fluid to the first inlet and the second fluid to the second inlet of the

8 device;

9 (iii) a valve operatively coupled to the pump, the valve configured to, in a first setting, 10 permit fluid flow from the first source of the first fluid and from the second source of 11. the second fluid to the pump, the valve further configured to, in a second setting, permit

12 fluid flow from the pump to the first inlet and to the second inlet of the device, the first

13 fluid provided to the first inlet and the second fluid provided to the second inlet;

14

15 22, The system of claim 21 , wherein the channel is formed as a logarithmic spiral with polar

16 coordinates (r, Θ and a logarithmic curve (r ) of the logarithmic spiral defined as:

17 23, The system of claim 21 , the first inlet including a first inlet port configured to fluidiy couple

18 the pump and the valve, and the second inlet including a second inlet port configured to

19 fluidiy couple the pump and the valve.

20 24. The system of claim 21 , the first outlet including a first outlet port, the second outlet

21 including a second outlet pott, wherein at least one of the first outlet port or the second outlet

22 port configured to fluidiy couple a detector for particles.

23 25. The system of claim 24, the first outlet port configured to fluidiy couple a detector to detect

24 particles drawn into the first fluid from the second fluid.

25 26. The system of claim 21 or 25, further comprising a detector fluidiy coupled to the first outlet

26 of the device, the detector configured to detect particles drawn into the first fluid from the

27 second fluid, which drawn particles exit the device at the first outlet. 27, The system of claim 26, wherein the detector is a mass spectrometer. 28. The system of claim 21, further comprising a first syringe and a second syringe operably coupled to the pump, the first syringe configured to receive the first fluid from the pump, the second syringe configured to receive the second fluid from the pump, the first syringe further configured to provide the first fluid to the first inlet, and the second syringe further configured to provide the second fluid to the second inlet. 29, The system of claim 28, the pump further fluidly coupled to a third source of a third fluid, the pump further configured to pull the third fluid from the third source, the second syringe further configured to receive the third fluid from the pump, wherein the pump and the second syringe further configured to provide at, least one of the second fluid or the third fluid to the second inlet. 30. The system of claim 29, further comprising a mixing structure fluidly coupled to the pump, the mixing structure further fluidly coupled to the second source and the third source, the mixing structure configured to substantially mix the second fluid and the third fluid. 31 , The system of claim 30, where in the mixing structure is a y-valve. 32. The system of claim 21 , wherein the valve is a switching valve. 33. The system of claim 33, wherein the switching valve is a two-way, six-port valve. 34. The system of claim 21 or 28, further comprising a controller operativeiy coupled to the pump and the valve, the controller configured to switch the valve to the first setting, in the first valve setting the controller further configured to direct the pump to pull at least one of the first fluid from the first source, the second fluid from the second source, or the third fluid from the third source, and the controller further configured to switch the valve to the second setting, in the second valve setting the controller further configured to direct the pump to provide at least one of the first fluid to the first inlet of the device, the second fluid to the second inlet of the device, or the third fluid to the second inlet of the device. 35. A method to separate particles, comprising: (a) receiving a first fluid and a second fluid in a channel of a device in laminar flow such that turbulent mixing of the first fluid and the second fluid does not occur, the second fluid ha ving particles of a substance suspended therein; (b) drawing at least a portion of particles suspended in the second fluid from the second fluid into the first fluid based on a characteristic of the suspended particles; and (c) separating the first fluid from the second fluid, the first fluid including the portion of drawn particles. 36, The method of claim 35, the receiving further including receiving the first fluid and the second fluid in a spiral channel. 37, The method of claim 36, wherein the channel is formed as a. logarithmic spiral with polar coordinates (r, Θ) and a logarithmic curve (r ) of the logarithmic spiral defined as: r = ae^b9 38. The method of claim 35, the receiving including receiving the first fluid and the second fluid at flow rates characterized by a Reynolds number less than about 1 for the first fluid and for the second fluid. 39. The method of claim 35 or 38, the receiving further including receiving the first fluid and the second fluid received at a flow rate of about 50 jiL/min. 40. The method of claim 35 or 36, the drawing further including drawing, via spiral inertial forces acting on suspended particles during use, at least a portion of the particles suspended in the second fluid into the first fluid based on the characteristic of the suspended particles. 41. The method of claim 40, wherein the characteristic of the suspended particles is a physical property. 42, The method of claim 41 , wherein the physical property is particle molecular mass. 43. The method of claim 42, wherein the particles suspended in the second fluid include particles of a plurality of masses, the drawing further including drawing at least a portion of particles less than a first mass from the second fluid into the first fluid. 44, The method claim 43, wherein the first mass is about 700 Daltons. 45. The method of claim 35, further comprising detecting a signal transmitted by particles suspended in the first fluid or in the second fluid, 46. The method of claim 45, further comprising processing the detected signal to detect at least one of the presence or amount of the particles suspended in the first fluid or the second fluid. 47. The method of claim 46, further comprising detecting, by a detector fluidly coupled to at least one of a first outlet or a second outlet of the device, the signal transmitted by particles suspended in the first fluid or particles suspended in the second fluid, wherein the first fluid is received at the first outlet and wherein the second fluid is received at the second outlet. 48. The method claim 47, further comprising detecting, by a detector fluidly coupled to the first outlet, the signal transmitted from particles drawn into the first fluid from the second fluid, wherein the drawn particles are received at the first outlet. 49. The method of claim 48, wherein the first fluid includes a solvent compatible with a detector. 50. The method of claim 45 or 49, wherein the detector includes a mass spectrometer. 51. The method of claim 45, wherein the detector includes a biosensor. 52. The method of claim 35, further comprising providing at least one of the first fluid or the second fluid to the channel of the device. 53, The method of claim 52, the providing further comprising providing at least one of the first fluid and the second fluid to the channel of the device at a flow rate such that laminar flow of the first fluid and the second fluid is achieved. 54. The method of claim 53, wherein the flow rate is about 50 uL/min. 55, The method of claim 52, further comprising providing, by a pump fluidly coupled to the channel of the device, at least one of the first fluid or the second fluid to the channel of the device, wherein the first fluid is provided to a first inlet of the channel and the second fluid is provided to a second inlet of the channel . 56, The method of claim 55, further comprising pulling, by the pump further fluidly coupled to at least one of a first source of the first fluid or a second source of the second fluid, at least one of the first fluid from the first source or the second fluid from the second source, wherein the first fluid pulled from the first source is provided to the first inlet and the second fluid pulled from the second source is provided to the second inlet. 57. The method of claim 56, further comprising directing the pump to pull at least one of the first fluid from the first source or the second fluid from the second source, or to provide at least one of the first fluid to the first inlet of the channel or the second fluid to the second inlet of the channel. 58. The method of claim 57, wherein the directing is accomplished using a controller operative!}' coupled to the pump. 59. The method of claim 57, further comprising permitting, by a valve operatively coupled to the pump, fluid flow from at least one of the first fluid from the first source to the device or the second fluid from the second source to the device, wherein the valve, in a first setting, permits fluid flow from the first source and from the second source to the pump, and wherein the valve further, in a second setting, permits fluid flow from the pump to the first inlet of the device and to the second inlet of the device, wherein the first fluid is provided to the first inlet of the device and the second fluid is provided to the second inlet of the device. 60, The method of claim 59, further comprising directing, by a controller operatively coupled to the valve, the valve to switch between the first setting and the second setting. 61 , The method of claim 35 or 55, further comprising combining the second fluid with a third fluid, 62, The method of claim 61, the providing further comprising providing, by the pump fluidly coupled to the channel of the device, at least one of the first fluid or the combined second fluid and third fluid to the channel of the device, wherein the combined second fluid and third fluid are further provided to the second inlet of the channel. 63, The method of claim 62, further comprising pulling, by the pump further fluidly coupled to a third source of the third fluid, the third fluid form the third source. 64, The method of claim 63, further comprising directing the pump to pull at least one of the first fluid from the first source, the second fluid from the second source, or the third fluid from the 1 third source, or directing the pump to provide the at least one of the first fluid to the first inlet

2 of the device or combined second fluid and third fluid to the second inlet of the device.

3 65, The method of clam 64, the directing further comprising directing, by a controller operably

4 coupled to the pump.

5 66, The method of claim 64, further comprising permitting, by a valve operativelv coupled to the

6 pump, fluid flow from at least one of the first fluid from the first source to the device, the

7 second fluid from the second source to the device, or the third fluid from the third source to

8 the device, wherein the valve, in a first setting, permits fluid flow from the first source, the

9 second source, and the third source to the pump, and wherein the valve further, in a second 10 setting, permits fluid flow from the pump to the first inlet and to the second inlet of the 11. device, wherein the first fluid flows to the first inlet of the device and the combined second

12 fluid and third fluid flows to the second inlet.

13 67, The method of claim 66, further comprising directing, by a controller operatively coupled to

14 the valve, wherein the controller directs the valve to switch between the first setting and the

15 second setting.

16 68. The method of claim 61 , further comprising substantially mixing the second fluid with the

17 third fluid.

18 69. The method of claim 68, wherein the mixing is accomplished using a mixing structure, the

19 mixing structure fluidly coupled to the second source of the second fluid and the third source

20 of the third fluid, the mixing structure further fluidly coupled to the pump and the valve

21 system, wherein the mixing structure substantially mixes the second fluid and the third fluid,

22 70. The method of claim 55 or 62, the providing further comprising providing, by the pump,

23 isocratic fluid flow through the device during use,

24 71. The method of claim 70, the providing further comprising providing, by the pump, periodic

25 injections of a sample into the device.

26 72. The method of any of claims 58, 65, 67, or 71 , wherein operation parameters are set

27 according to instructions programmed into the pump and the valve system. 73, The method of claim 35, wherein the particles drawn from the second fluid into the first fluid are cellular metabolites. 74, The method claim 73, wherein the second fluid is a biological fluid. 75. The method of claim 74, wherein the biological fluid is derived from an organism. 76. The method of claim 74, wherein the biological fluid is whole blood. 77. The method of claim 74, wherein the biological fluid is urine. 78. The method of claim 74, wherein the biological fluid includes cells suspended therein. 79, The method of claim 65 , wherein the third fluid is a lysing solution. 80. The method of claim 69 or 79, wherem the second fluid includes cells suspended therein, wherein the mixing structure substantially mixes the second fluid and the third fluid such that cellular metabolites are liberated from the cells into the mixed second fluid and third fluid. 81. The method of claim 80, wherein the cells are prokaryotic cells. 82. The method of claim 81 , wherein the prokaryotic cells are bacterial cells. 83, The method of claim 80, wherein the cells are eukaryotic cells. 84. The method of claim 83, wherein the eukaryotic cells are mammalian cells, 85, The method of claim 84, wherein the mammalian cells are red blood cells,