US20020183604A1 - Apparatus for access to interstitial fluid, blood, or blood plasma components - Google Patents

Apparatus for access to interstitial fluid, blood, or blood plasma components Download PDF

Info

Publication number
US20020183604A1
US20020183604A1 US10/209,819 US20981902A US2002183604A1 US 20020183604 A1 US20020183604 A1 US 20020183604A1 US 20981902 A US20981902 A US 20981902A US 2002183604 A1 US2002183604 A1 US 2002183604A1
Authority
US
United States
Prior art keywords
implant
septum
central housing
filtration membrane
disposed
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/209,819
Inventor
Ashok Gowda
Roger McNichols
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to US10/209,819 priority Critical patent/US20020183604A1/en
Publication of US20020183604A1 publication Critical patent/US20020183604A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
    • A61B5/14865Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14525Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis
    • A61B5/14528Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis invasively
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150015Source of blood
    • A61B5/150022Source of blood for capillary blood or interstitial fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150351Caps, stoppers or lids for sealing or closing a blood collection vessel or container, e.g. a test-tube or syringe barrel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150839Aesthetic features, e.g. distraction means to prevent fears of child patients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/151Devices specially adapted for taking samples of capillary blood, e.g. by lancets, needles or blades
    • A61B5/15142Devices intended for single use, i.e. disposable
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6848Needles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/686Permanently implanted devices, e.g. pacemakers, other stimulators, biochips
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6865Access ports
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02Access sites
    • A61M39/0247Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02Access sites
    • A61M39/0247Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • A61M2039/0258Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body for vascular access, e.g. blood stream access
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02Access sites
    • A61M39/0247Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • A61M2039/0261Means for anchoring port to the body, or ports having a special shape or being made of a specific material to allow easy implantation/integration in the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M39/00Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/02Access sites
    • A61M39/0247Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body
    • A61M2039/0276Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body for introducing or removing fluids into or out of the body

Definitions

  • the invention is directed to an apparatus for intradermal implantation of a device to facilitate repeated, painless, safe, and reliable access to interstitial fluid, blood, or blood plasma for monitoring of blood borne or tissue analyte concentrations including but not limited to glucose, cholesterol, lactate, bilirubin, blood gases, ureas, creatinine, phosphates, myoglobin and hormones or delivery of drugs or other injectable agents such as chemotherapeutic agents, photosensitizing agents, hormones, vaccines, or radiological or other contrast agents.
  • the present invention is directed to a method and apparatus for analyte detection which substantially overcomes one or more of the problems due to the limitations and disadvantages of the related art. More specifically, the present invention is directed to a transcutaneous implant, methods for implanting and using the transcutaneous implant and fluid withdrawal/delivery implements and replaceable components for use with the transcutaneous implant.
  • the transcutaneous implant includes an access component to provide a stable dermal interface, a central housing disposed within the access component, a septum disposed within the central housing, and a filtration membrane disposed at a distal end of the central housing to promote mass transfer of analyte in bodily fluid into a reservoir formed by the filtration membrane, the septum and the central housing.
  • FIG. 1A is an elevational perspective side view of the implantable access port in accordance with the present invention.
  • FIG. 1B is an elevational cross-section of the implantable access port shown in FIG. 1A;
  • FIG. 1C is an elevational perspective side view of the transcutaneous access component according to one embodiment of the present invention.
  • FIG. 1D is an elevational perspective side view of the advanced filtration membrane component of the present invention.
  • FIG. 1E is an elevational perspective side view of the housing component which contains safety valves and reservoir of the present invention.
  • FIG. 2A is an elevational cross-section of another embodiment of a port for access to the blood space in accordance with the present invention.
  • FIG. 2B is an elevational cross section of another embodiment of the access port that includes a specially shaped filtration membrane to enhance mass transfer;
  • FIG. 2C is an elevational side view of another embodiment of the access port in which a safety stop is included within the collection chamber to prevent damage to the filtration membrane and the collection chamber is coated with an antibacterial agent;
  • FIG. 2D is a cross-sectional view of an another embodiment the of the access port of the present invention.
  • FIG. 2E is a cross-sectional view of yet another embodiment the of the access port of the present invention.
  • FIG. 2F is a cross-sectional view of an another embodiment the of the access port of the present invention.
  • FIG. 3A illustrates a side view of the access port of the present invention which has been implanted
  • FIG. 3B illustrates a side view of the access port of the present invention which has been implanted and is in use with a device for collection or delivery of fluid;
  • FIG. 4A illustrates a side view of an implanted access port according to an embodiment that includes an external sampling stop
  • FIG. 4B illustrates insertion of a sampling device that includes a needle into the implanted access port of FIG. 4A;
  • FIG. 5A illustrates a side view of an implanted access port used in conjunction with an external analyte measurement device
  • FIG. 5B illustrates a side view of an implanted access port according to an embodiment that includes a replaceable electro-enzymatic sensor
  • FIG. 5C illustrates a close up side view of the replaceable sensor included in the implanted access port of FIG. 5B.
  • FIG. 5D illustrates the implantable access port and replaceable electroenzymatic sensor of FIG. 5B used in conjunction with a wristwatch style measurement device.
  • a transcutaneous implant is provided, obviating the need for puncturing the skin to obtain fluid samples.
  • the implant promotes a stable biological seal at the skin interface and prevents capsule formation and exit site infection.
  • the implant includes an advanced filtration membrane that eliminates the mass transfer problem by promoting capillary networks with transcapillary mass transfer rates high enough to insure rapid exchange of analyte between blood and the device.
  • microporous materials allow blood vessels to grow and be maintained at the tissue-material interface and in some cases within the pores of the material. However this is not true for all porous polymer membranes, even those with similar porosities and chemistries. What influences the host response is not necessarily the chemistry of the material, but the microstructure of individual features within the material onto which host cells can attach. Materials that are microporous but contain large planar features promote an avascular host response while the same material lacking these planar features and having a more fibrous structure promote neovascularization at the tissue-material interface. Thus, in embodiments of the present invention, microporous polymers having a fibrous structure are integrated into the implanted transport membrane to reduce fibrosis and enhance neovascularization.
  • an implantable access port (IAP) 1 includes three main components.
  • the device includes an access component 5 for providing a stable dermal interface for the transcutaneous implant.
  • the device uses an advanced filtration membrane 10 engineered to promote improved mass transfer between analytes in the blood and those collected by the device.
  • a central housing 15 with septa 20 that form self-sealing apertures and a reservoir 25 for storage of fluid prior to collection is provided.
  • Annular support members 19 are affixed to the central housing 15 (or formed integrally with the central housing) to support and position the septa 20 .
  • the preferred embodiment of this invention is described below. Alternate embodiments are listed as well.
  • the design of the IAP is based on providing a stable interface for the implant at an externally located site and incorporating a suitable membrane for long-term biocompatibility and filtration performance.
  • the access component 5 shown in FIG. 1C includes a flat, disc-shaped skirt 30 having a central opening 35 and an array of through holes 40 distributed around the discshaped skirt 30 . Extending out from one side of the skirt 30 in registration with the opening is an integral tubular neck 45 whose lumen 50 is in registration with the opening of the skirt 35 .
  • the access component 5 is preferably formed of a flexible, thermally stable, biocompatible material such as flexible medical grade polyurethane, polymethyl methacrylate (PMMA), polyethylene (PE), polyvinyl chloride (PVC), polycarbonate, polypropylene (PP) polydimethyl siloxane (PDMS), ethylene glycol dimethacrylate (EGDM), polytetrafluoroethylene PTFE), nylon or the like.
  • a flexible medical grade polyurethane polymethyl methacrylate (PMMA), polyethylene (PE), polyvinyl chloride (PVC), polycarbonate, polypropylene (PP) polydimethyl siloxane (PDMS), ethylene glycol dimethacrylate (EGDM), polytetrafluoroethylene PTFE), nylon or the like.
  • PMMA polymethyl methacrylate
  • PE polyethylene
  • PVC polyvinyl chloride
  • PP polypropylene
  • PDMS polydimethyl siloxane
  • EGDM ethylene glycol dime
  • the entire body of the skirt 30 and neck 45 is covered by a porous covering or bed 55 of material such as polyester velour (U.S. Catheter and Instrumentation Company of Glenfalls, N.Y. Part # 600k61121).
  • the thickness of the covering 55 preferably may range from 0.01 mm to 1.5 mm, and even more preferably is about 0.1 mm.
  • the covering encourages cell infiltration and the formation of subcutaneous tissue and collagen.
  • the overall design of the access component 5 may be as set forth in U.S. Pat. No. 5,662,616, which is hereby incorporated herein by reference.
  • the skirt 30 preferably has a diameter ranging from 0.2 to 4.0 cm, even more preferably about 2.5 cm.
  • the thickness of the skirt 30 preferably may range from 0.05 to about 0.5 cm, and even more preferably is about 0.2 cm.
  • the central opening of the skirt and lumen 35 of the neck preferably may range from 0.1 to 3.0 cm in diameter, and even more preferably are about 0.7 cm.
  • the outer diameter of the neck 45 preferably may range from 0.25 to 2.0 cm, and even more preferably is about 1.0 cm.
  • the height of the entire access component 5 preferably ranges from about 0.25 to about 2.5 cm, and even more preferably is about 1.0 cm.
  • FIG. 1D illustrates the advanced filtration membrane 10 according to one embodiment.
  • the membrane 10 is designed to allow for passive diffusion of analytes in interstitial fluid (ISF) while preventing transport of cells and larger proteins.
  • the filtration membrane 10 is preferably constructed from a polyvinylidene fluoride (PVDF) membrane 60 , although other materials may be used including, but not limited to, cellulose acetate, mixed esters of cellulose, polysulfone, polyester, polypropylene, cellulose nitrate, polycarbonate, nylon (charged and uncharged), polyethylene, and vinyl acetate ethylene copolymers.
  • PVDF membrane 60 is used to promote microachitecture-driven neovascularization 62 .
  • the surface of the PVDF membrane 60 adjacent the reservoir 25 is laminated with an ultrafiltration membrane 65 consisting of any biocompatible material with pore sizes of less than 1.0 ⁇ m.
  • the ultrafiltration membrane is constructed using a hydrogel of photopolymerized polyethylene glycol (PEG).
  • PEG photopolymerized polyethylene glycol
  • the molecular weight of the PEG membrane may range in size from 100 Da to 50 Kda or more preferably 575 Da. (Sigma Chemical).
  • the laminated filtration membranes 10 are formed by spin coating aqueous hydrogel precursor solutions on the inside of the PVDF membrane 60 (e.g., a precursor solution consisting of 23% PEG-dacrylate and 0.1% 2,2′-dimethoxy-2Diphenylacetophenone (Sigma Chemical Part # 24650-42-8), a UV-activated free radical polymerization agent).
  • aqueous hydrogel precursor solutions e.g., a precursor solution consisting of 23% PEG-dacrylate and 0.1% 2,2′-dimethoxy-2Diphenylacetophenone (Sigma Chemical Part # 24650-42-8), a UV-activated free radical polymerization agent.
  • the high viscosity of the solution and surface tension between the PVDF membrane and the precursor solution does not allow significant solution penetration into the pores of the PVDF membrane and therefore does not inhibit neovascularization.
  • the coated PVDF membrane 60 is then illuminated by UV light (e.g., 365 nm, 20 mW/cm 2 ) at a distance of approximately 1 cm until complete polymerization has taken place (typically two to ten seconds or less).
  • UV light e.g., 365 nm, 20 mW/cm 2
  • the filtration membrane 10 is then attached to the housing 15 using a medical grade adhesive (e.g., an epoxy such as Loctite # 4981).
  • the PVDF membrane 60 has a pore size ranging from 0.05 ⁇ m to 40 ⁇ m, preferably about 5 ⁇ m.
  • the thickness of the filtration membrane 10 preferably may range from 10 ⁇ m to 500 ⁇ m, and even more preferably is about 100 ⁇ m.
  • the diameter of the filtration membrane 10 preferably ranges from 0.1 to 3.0 cm in diameter, and even more preferably is about 0.7 cm.
  • the filtration membrane is designed to promote neovascularization on the tissue interfacing side while preventing cellular passage with a bioprotective layer on the device side.
  • PEG is preferable but many materials with pore sizes too small for cells to pass through may be used.
  • photopolymerized PEG is suitable but other techniques of polymerization of the PEG are acceptable, for example, thermal or chemical methods may be used to initiate polymerization of the PEG.
  • the central housing 15 includes a conduit 70 with septa 20 contained within the conduit 70 .
  • the distal end of the conduit 75 is sealed with the filtration membrane 10 .
  • the portion of the conduit between the top of the filtration membrane 10 and the bottom of the lower septum 20 form the collection reservoir 25 .
  • the top of the conduit 70 contains a cap 80 to prevent debris and contaminants from entering the conduit 70 when the implant 1 is not in use.
  • the cap depicted in FIG. 1E is a hinged, spring-loaded cap, numerous other cap designs may be used including, without limitation, a removable, snap-on or screw on cap.
  • the conduit 70 is preferably formed of stainless steel tubing or other rigid biocompatible material.
  • the conduit may be formed integrally with the housing unit 15 , being defined by the lumen thereof.
  • the outer diameter of the housing element 15 may range from 0.1 to 2.0 cm, and is preferably about 0.7 cm.
  • the lumen diameter of the housing element 15 may range from 0.125 to 1.775 cm, and is preferably about 0.5 cm.
  • Each of the septum 20 is preferably constructed of a elastic, self-sealing biocompatible material, more preferably silicone rubber and is sized to fit snugly within the lumen of the conduit, thus providing a liquid-tight seal between the collection reservoir 25 and the upper portion of the conduit.
  • the thickness of the individual septum 20 preferably may range from 0.05 to 1.0 cm and more preferably is about 0.3 cm.
  • the distance between the bottom of the lower septum 20 and the filtration membrane 10 defines the depth of the collection reservoir 25 and preferably may range from 0.05 cm to 2.0 cm and more preferably is about 0.2 cm.
  • the resulting volume of the collection reservoir 25 may range from 0.6 ⁇ l to 5.0 ml and more preferably is about 40 ⁇ l.
  • FIG. 2A illustrates an alternative embodiment of an implantable access port designed to be used for filtration of blood components.
  • the implant includes a transcutaneous access component 85 with a central housing component 90 connected to an arterio-venous shunt 95 .
  • the distal end of the housing component 100 is secured to the wall of the arterio-venous shunt such that an appropriate filtration membrane 103 resides within the lumen of the arterio-venous shunt 105 . Blood flowing through the arterio-venous shunt 95 is thereby filtered by the filtration membrane 103 and fluid is subsequently collected through the housing 90 .
  • FIG. 2B illustrates a further embodiment of an implantable access port described above modified such that the filtration membrane 110 is shaped to increase the surface area and hence mass transport between the tissue space and collection reservoir of analytes in interstitial fluid, blood, or blood plasma.
  • FIG. 2C illustrates a further embodiment of the collection reservoir in which a safety stop 115 is incorporated to prevent the aspirating device such as needles or capillary tubes from damaging the filtration membrane and a coating of silver 120 is used to prevent bacterial accumulation in the collected fluid.
  • the safety stop includes apertures along its circumference to permit analyte to pass in either direction between the reservoir and the aspirating device (or an agent delivery device).
  • the aspirating or delivery device having a side opening to the fluid intake or exhaust port to avoid blockage when the tip of the aspirating or delivery device contacts the bottom of the safety stop.
  • apertures smaller than the tip of the aspirating or agent delivery device may be distributed throughout the surface of the safety stop, permitting a fluid intake or exhaust port to be located anywhere on the aspirating or agent delivery device, including on the bottom of its tip.
  • FIG. 2D is a cross-section of the implantable access port shown in FIG. 1A demonstrating alternative configurations for layers contained in the advanced filtration membrane 10 .
  • the advanced filtration membrane 10 may be composed of a discrete twolayer filtration membrane 140 . In this configuration the PVDF membrane 60 is coated with a discrete layer of PEG membrane 65 .
  • the advanced filtration membrane 10 may be composed of a partially embedded 2-layer filtration membrane 141 in which the PEG ultrafiltration membrane 65 partially penetrates a small distance into the PVDF membrane 60 .
  • the advanced filtration membrane 10 may be composed of a fully embedded 2-layer filtration membrane 142 . In this configuration the full thickness of the PEG ultrafiltration membrane 65 is contained within a thickness of the PVDF membrane 60 .
  • the advanced filtration membrane 10 may be composed of a three layer filtration membrane 143 .
  • a membrane support screen 64 is included to provide additional support to the filtration membrane 10 .
  • the membrane support screen may consist of any semi-rigid or rigid material but is preferably made using a stainless steel screen.
  • FIG. 2E is a cross-section of the implantable access port shown in FIG. 1A demonstrating alternative configurations for the housing 15 in which a replaceable septa insert 130 is incorporated.
  • the septa 20 are contained within a replaceable insert 130 .
  • the replaceable insert 130 may contain a threaded wall 135 such that once the septa 20 become worn to the point that they no longer self-seal, the user may unscrew the insert 130 and replace it with a new one.
  • the new septa insert 130 is screwed into the threaded wall of the housing until it abuts a stop wall 131 , thus allowing the inert 130 to be properly disposed within the lumen of the housing 15 (or conduit as shown in FIG. 1E).
  • Other mechanisms for securing the replaceable insert may also be used including, without limitation, friction holds, mechanical catches and the like.
  • FIG. 2F is a cross-section of the housing 15 in which only a single self-sealing septum 20 is used. Any of the alternative embodiments may contain a single self-sealing septum 20 as opposed to the two-septum configuration as shown in FIG. 1B.
  • the access port 1 is implanted so that the skirt 30 of the access component 5 is anchored in the subcutaneous tissue 200 and the neck 45 of the access component 5 penetrates the dermal 205 and epidermal layer 210 of the skin.
  • fibrous collagen begins to deposit in the holes 40 in the skirt 30 to help anchor the access component 5 .
  • the velour covering 55 provides a porous, fibrous-structure bed to encourage the growth of tissue and collagen around the skirt 30 to provide a biological seal with the epidermal cells which migrate and invaginate along the neck 50 until they reach the covering.
  • the housing component 15 which is fixed within the access component 5 , provides for collection of fluid from the body without requiring breaking the skin barrier.
  • the filtration membrane 10 attached to the housing 15 allows passage of interstitial fluid, blood, or blood plasma while preventing larger cells and proteins from entering the collection reservoir 25 .
  • the fluid filtered by the membrane and stored in the collection reservoir becomes the sample for analyte measurement using any applicable small volume sensor.
  • the access port 1 is designed to be used in conjunction with a sampling device 215 .
  • the sampling device 215 may be a needle or catheter, but is preferably a specially designed capillary tube 220 with an integral stop 225 such that it can not be introduced far enough to damage the filtration membrane 10 .
  • the sampling device 215 is passed through the self-sealing septa such that the distal end of the sampling device 230 is positioned within the collection reservoir 25 but does not come in contact with the filtration membrane 10 . Fluid is drawn within a collection chamber of the sampling device 215 by capillary action or aspirating the proximal end of the sampling device 215 (e.g., by slideably withdrawing a plunger from the chamber of the sampling device 215 ).
  • the implantable access port described herein may be used to deliver agents into the body.
  • agents might include, but are not limited to, drugs, hormones, chemotherapeutic agents, photosensitizing agents, vaccines, radiological, or contrast agents.
  • the agent to be administered would be placed within the collection reservoir 25 (now being used as a delivery reservoir) and the membrane 10 would be designed to allow passage of the agent into the subcutaneous fluid or blood space.
  • the implantable access port is the operation of the implantable access port to deliver insulin or for use in combination with insulin pumps.
  • the implantable access port described herein may be implanted anywhere on the body having a soft tissue layer sufficiently thick to accommodate the protrusion of the access port into the subdermal space.
  • the implant is placed on the wrist or arm area for easy patient access and may include a device or implement to cover the port such as a wrist watch interface or skin colored bandage to improve patient acceptance of the aesthetic qualities of the device.
  • the access port is preferably placed somewhere on the body which is not subject to a lot of exposure or contact such as the abdomen.
  • the implantable access port provides a method for withdrawal of body fluids without requiring breach of the skin barrier.
  • the implantable access port also provides for filtration of interstitial fluid, blood, or blood plasma resulting in a sample of fluid containing an analyte of interest. Because of its porosity and fibrous structure, the access port forms an infection-free, transcutaneous implant having a biological seal around the device. Therefore, the implant is suitable for long term use. Since the implant resides in the plane between the subcutaneous and dermal layers of tissue, subsequent removal is simple if necessary. Additionally, the access port has relatively few components and may be easily manufactured with common, readily available materials. Once implanted, the withdrawal of fluid from the body can be performed in a painless and reliable manner.
  • FIG. 4A illustrates a side view of an embodiment of an implanted access port which includes an external sampling stop 235 for providing safe access to the interstitial fluid without damaging the filtration membrane 10 .
  • the external sampling stop 235 permits a needle 217 to be used with the sampling device 215 in a safe manner.
  • the sampling device 215 is inserted into the external sampling stop 235 until a flange at the forward end of the sampling device abuts a stop wall 237 .
  • the needle 217 extends through an aperture in the stop wall 237 , passes through the self-sealing septa 20 and comes to rest with the tip located just within the reservoir 25 .
  • the needle is preferably a non-coring needle (Part No. 7165, Popper & Sons, Inc., New Hyde Park, N.Y.) to prevent coring of the self-sealing septa 20 .
  • the sampling stop 235 can be custom designed according to the needle 217 and sampling device 210 used. In one embodiment, the sampling stop is removable, for example by unplugging or unscrewing from the implant 1 , thus permitting sampling stops having various profiles and receptacle shapes to be used interchangeably. In an alternative embodiment, the sampling stop 235 forms part of the implant and is capped by an end cap as discussed above (see, for example, FIG. 1E, element 80 ).
  • FIG. 5A illustrates a side view of the implanted access port used in conjunction with an external analyte measurement device.
  • an external analyte measurement device 240 is interfaced with the sampling device 215 . This configuration allows for interstitial fluid withdrawn from the device and containing the analyte of interest to be directly communicated to an external analyte measurement device 240 .
  • FIG. 5B illustrates a side view of an implanted access port that incorporates a replaceable electro-enzymatic sensor 245 .
  • the sensor chemistry 260 is contained with the electroenzymatic sensor 245 and is placed within the reservoir 25 containing the interstitial fluid.
  • Such a sensor chemistry is described in detail by Quinn et al. (Photo-crosslinked copolymers of 2 hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors), the entire content of which is hereby incorporated by reference. In the embodiment shown in FIG.
  • FIG. 5B illustrates a close up side view of the replaceable sensor 245 .
  • the sensor 245 may also contain a fluid withdrawal port 252 that would allow the user to withdraw interstitial fluid periodically in order to calibrate the electroenzymatic sensor 245 .
  • the sensor 245 can be removed from the access port 1 and calibrated in known standards.
  • FIG. 5D illustrates the implantable access port and replaceable electroenzymatic sensor of FIG. 5B used in conjunction with a wristwatch style measurement display device.
  • a wristwatch style analyte measurement display device 265 may be continuously worn over the access port 1 and replaceable sensor 245 to display continuous measurement of the analyte of interest.
  • Numerous other styles and configurations of measurement display devices may be worn over the access port in alternative embodiments.

Abstract

A transcutaneous implant having a stable biological seal at the skin interface, obviating the need for puncturing the skin to obtain fluid samples is described. The implant includes an advanced filtration membrane to promote neovascularization which eliminates mass transfer problems by promoting the development of capillary networks with transcapillary mass transfer rates high enough to insure rapid exchange of analyte between blood and the device. Additionally the membrane provides a bioprotective layer which prevents transport of proteins and cellular components into the device.

Description

    BACKGROUND OF THE INVENTION
  • The invention is directed to an apparatus for intradermal implantation of a device to facilitate repeated, painless, safe, and reliable access to interstitial fluid, blood, or blood plasma for monitoring of blood borne or tissue analyte concentrations including but not limited to glucose, cholesterol, lactate, bilirubin, blood gases, ureas, creatinine, phosphates, myoglobin and hormones or delivery of drugs or other injectable agents such as chemotherapeutic agents, photosensitizing agents, hormones, vaccines, or radiological or other contrast agents. [0001]
  • There is now a large body of evidence that intensive management of blood sugars is an effective means to slow or even prevent the progression of diabetic complications such as kidney failure, heart disease, gangrene, and blindness. The design and development of a simple apparatus for obtaining interstitial fluid, blood or blood plasma samples without breaking the skin would be a large advancement in trying to improve diabetic patient compliance for monitoring blood glucose levels. [0002]
  • Maintaining blood glucose concentrations near normal levels in diabetic patients can only be achieved with frequent blood glucose monitoring so that appropriate actions can be taken, such as insulin injections, or sugar ingestion. Unfortunately the current methods of sensing are based on colorimetric or electro-enzymatic approaches that require a blood or interstitial fluid sample each time a reading is needed. Withdrawal of a blood or interstitial fluid sample currently requires invasive methods of penetrating the skin surface. These methods are both time-consuming and painful and therefore there is a significant lack of compliance among the diabetic population for monitoring their blood glucose levels for the recommended five or more times daily. [0003]
  • Several research groups have focused efforts on methods for minimally invasive withdrawal of (primarily) interstitial fluid including the use of electrical current, suction, penetration, microdialysis, and laser-assisted drilling of the stratum corneum. While these techniques have shown some preliminary promise, questions still remain as to the volume of fluid which can be obtained, the repeatability of samples obtained, and the lack of any significant improvement in skin trauma related to the sampling methods. Additionally, the accuracy of glucose measurements on such small samples of interstitial fluid will likely be highly sensitive to contaminants from sweat or dirt on the surfaces being sampled and requires development of new measurement technology appropriate for such small or low concentration samples. Therefore, the ability to directly withdraw interstitial fluid samples in an easy, reliable and safe manner would be a significant advance in minimally invasive sensing techniques. [0004]
  • Other groups are developing totally implantable sensors for measurement of blood or interstitial fluid glucose concentration. Normally, however, when a foreign body such as a medical implant is introduced into a host, the natural tendency of the surrounding tissue is to degrade or extrude the implant. If the host cannot eliminate the foreign body, a chronic inflammatory reaction results and the object is encapsulated in fibrous tissue with foreign body giant cells residing at the tissue-material interface. This capsule poses a difficult problem in the development of implanted sensing or sampling devices. In the case of interstitial fluid sampling, the fibrous capsule presents a mass transfer barrier and therefore limits the concentration of analyte reaching the collection site. Also, encapsulated implants may exhibit a significant lag time in the response to changes in blood glucose concentration. The ability of the capsule to limit mass transfer has been demonstrated in several studies (see, for example, Wood et al., Assessment of a Model for Measuring Drug Diffusion Through Implant-Generated Fibrous Capsule Membranes, [0005] Biomaterials. 16:957-9, (1995)).
  • SUMMARY OF THE INVENTION
  • The present invention is directed to a method and apparatus for analyte detection which substantially overcomes one or more of the problems due to the limitations and disadvantages of the related art. More specifically, the present invention is directed to a transcutaneous implant, methods for implanting and using the transcutaneous implant and fluid withdrawal/delivery implements and replaceable components for use with the transcutaneous implant. In one embodiment, the transcutaneous implant includes an access component to provide a stable dermal interface, a central housing disposed within the access component, a septum disposed within the central housing, and a filtration membrane disposed at a distal end of the central housing to promote mass transfer of analyte in bodily fluid into a reservoir formed by the filtration membrane, the septum and the central housing. [0006]
  • These and other features and advantages of the present invention will be apparent from the accompanying drawings and from the detailed description and claims that follow. [0007]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements and in which: [0008]
  • FIG. 1A is an elevational perspective side view of the implantable access port in accordance with the present invention; [0009]
  • FIG. 1B is an elevational cross-section of the implantable access port shown in FIG. 1A; [0010]
  • FIG. 1C is an elevational perspective side view of the transcutaneous access component according to one embodiment of the present invention; [0011]
  • FIG. 1D is an elevational perspective side view of the advanced filtration membrane component of the present invention; [0012]
  • FIG. 1E is an elevational perspective side view of the housing component which contains safety valves and reservoir of the present invention; [0013]
  • FIG. 2A is an elevational cross-section of another embodiment of a port for access to the blood space in accordance with the present invention; [0014]
  • FIG. 2B is an elevational cross section of another embodiment of the access port that includes a specially shaped filtration membrane to enhance mass transfer; [0015]
  • FIG. 2C is an elevational side view of another embodiment of the access port in which a safety stop is included within the collection chamber to prevent damage to the filtration membrane and the collection chamber is coated with an antibacterial agent; [0016]
  • FIG. 2D is a cross-sectional view of an another embodiment the of the access port of the present invention; [0017]
  • FIG. 2E is a cross-sectional view of yet another embodiment the of the access port of the present invention; [0018]
  • FIG. 2F is a cross-sectional view of an another embodiment the of the access port of the present invention; [0019]
  • FIG. 3A illustrates a side view of the access port of the present invention which has been implanted; [0020]
  • FIG. 3B illustrates a side view of the access port of the present invention which has been implanted and is in use with a device for collection or delivery of fluid; [0021]
  • FIG. 4A illustrates a side view of an implanted access port according to an embodiment that includes an external sampling stop; [0022]
  • FIG. 4B illustrates insertion of a sampling device that includes a needle into the implanted access port of FIG. 4A; [0023]
  • FIG. 5A illustrates a side view of an implanted access port used in conjunction with an external analyte measurement device; [0024]
  • FIG. 5B illustrates a side view of an implanted access port according to an embodiment that includes a replaceable electro-enzymatic sensor; [0025]
  • FIG. 5C illustrates a close up side view of the replaceable sensor included in the implanted access port of FIG. 5B; and [0026]
  • FIG. 5D illustrates the implantable access port and replaceable electroenzymatic sensor of FIG. 5B used in conjunction with a wristwatch style measurement device. [0027]
  • DETAILED DESCRIPTION
  • The invention disclosed herein eliminates many of the problems associated with prior art methods for fluid withdrawal. In one embodiment, a transcutaneous implant is provided, obviating the need for puncturing the skin to obtain fluid samples. The implant promotes a stable biological seal at the skin interface and prevents capsule formation and exit site infection. The implant includes an advanced filtration membrane that eliminates the mass transfer problem by promoting capillary networks with transcapillary mass transfer rates high enough to insure rapid exchange of analyte between blood and the device. There are several strategies for promoting this neovascularization, including prevascularization, the release of angiogenic factors, and microarchitecture-driven neovascularization. [0028]
  • Certain microporous materials allow blood vessels to grow and be maintained at the tissue-material interface and in some cases within the pores of the material. However this is not true for all porous polymer membranes, even those with similar porosities and chemistries. What influences the host response is not necessarily the chemistry of the material, but the microstructure of individual features within the material onto which host cells can attach. Materials that are microporous but contain large planar features promote an avascular host response while the same material lacking these planar features and having a more fibrous structure promote neovascularization at the tissue-material interface. Thus, in embodiments of the present invention, microporous polymers having a fibrous structure are integrated into the implanted transport membrane to reduce fibrosis and enhance neovascularization. [0029]
  • An embodiment of the present invention is illustrated in FIGS. [0030] 1A-1E. As shown in FIG. 1A, an implantable access port (IAP) 1 includes three main components. First, the device includes an access component 5 for providing a stable dermal interface for the transcutaneous implant. Second, the device uses an advanced filtration membrane 10 engineered to promote improved mass transfer between analytes in the blood and those collected by the device. Finally, a central housing 15 with septa 20 that form self-sealing apertures and a reservoir 25 for storage of fluid prior to collection is provided. Annular support members 19 are affixed to the central housing 15 (or formed integrally with the central housing) to support and position the septa 20.
  • Using needles, capillary tubes or other aspirating device, interstitial fluid, blood or blood plasma can be sampled from the [0031] access port 1 in a painless fashion since the skin at the exit site is effectively removed. Practice of this device by a diabetic patient would allow the patient to monitor blood glucose levels more frequently and maintain approximately normal 24-hour blood-glucose profiles thereby reducing complications related to the disease.
  • The preferred embodiment of this invention is described below. Alternate embodiments are listed as well. The design of the IAP is based on providing a stable interface for the implant at an externally located site and incorporating a suitable membrane for long-term biocompatibility and filtration performance. [0032]
  • Access Component [0033]
  • The [0034] access component 5 shown in FIG. 1C includes a flat, disc-shaped skirt 30 having a central opening 35 and an array of through holes 40 distributed around the discshaped skirt 30. Extending out from one side of the skirt 30 in registration with the opening is an integral tubular neck 45 whose lumen 50 is in registration with the opening of the skirt 35. The access component 5, including the skirt 30 and neck 45, is preferably formed of a flexible, thermally stable, biocompatible material such as flexible medical grade polyurethane, polymethyl methacrylate (PMMA), polyethylene (PE), polyvinyl chloride (PVC), polycarbonate, polypropylene (PP) polydimethyl siloxane (PDMS), ethylene glycol dimethacrylate (EGDM), polytetrafluoroethylene PTFE), nylon or the like.
  • Preferably, the entire body of the [0035] skirt 30 and neck 45 is covered by a porous covering or bed 55 of material such as polyester velour (U.S. Catheter and Instrumentation Company of Glenfalls, N.Y. Part # 600k61121). In one embodiment, the thickness of the covering 55 preferably may range from 0.01 mm to 1.5 mm, and even more preferably is about 0.1 mm. The covering encourages cell infiltration and the formation of subcutaneous tissue and collagen. The overall design of the access component 5 may be as set forth in U.S. Pat. No. 5,662,616, which is hereby incorporated herein by reference.
  • In the present invention, the [0036] skirt 30 preferably has a diameter ranging from 0.2 to 4.0 cm, even more preferably about 2.5 cm. The thickness of the skirt 30 preferably may range from 0.05 to about 0.5 cm, and even more preferably is about 0.2 cm. The central opening of the skirt and lumen 35 of the neck preferably may range from 0.1 to 3.0 cm in diameter, and even more preferably are about 0.7 cm. The outer diameter of the neck 45 preferably may range from 0.25 to 2.0 cm, and even more preferably is about 1.0 cm. The height of the entire access component 5 preferably ranges from about 0.25 to about 2.5 cm, and even more preferably is about 1.0 cm.
  • Advanced Filtration Membrane [0037]
  • FIG. 1D illustrates the [0038] advanced filtration membrane 10 according to one embodiment. The membrane 10 is designed to allow for passive diffusion of analytes in interstitial fluid (ISF) while preventing transport of cells and larger proteins. The filtration membrane 10 is preferably constructed from a polyvinylidene fluoride (PVDF) membrane 60, although other materials may be used including, but not limited to, cellulose acetate, mixed esters of cellulose, polysulfone, polyester, polypropylene, cellulose nitrate, polycarbonate, nylon (charged and uncharged), polyethylene, and vinyl acetate ethylene copolymers. The PVDF membrane 60 is used to promote microachitecture-driven neovascularization 62. To prevent cells from entering the collection reservoir 25, the surface of the PVDF membrane 60 adjacent the reservoir 25 is laminated with an ultrafiltration membrane 65 consisting of any biocompatible material with pore sizes of less than 1.0 μm. Preferably, the ultrafiltration membrane is constructed using a hydrogel of photopolymerized polyethylene glycol (PEG). The molecular weight of the PEG membrane may range in size from 100 Da to 50 Kda or more preferably 575 Da. (Sigma Chemical). In one embodiment, the laminated filtration membranes 10 are formed by spin coating aqueous hydrogel precursor solutions on the inside of the PVDF membrane 60 (e.g., a precursor solution consisting of 23% PEG-dacrylate and 0.1% 2,2′-dimethoxy-2Diphenylacetophenone (Sigma Chemical Part # 24650-42-8), a UV-activated free radical polymerization agent). The high viscosity of the solution and surface tension between the PVDF membrane and the precursor solution does not allow significant solution penetration into the pores of the PVDF membrane and therefore does not inhibit neovascularization. The coated PVDF membrane 60, is then illuminated by UV light (e.g., 365 nm, 20 mW/cm2) at a distance of approximately 1 cm until complete polymerization has taken place (typically two to ten seconds or less). The filtration membrane 10 is then attached to the housing 15 using a medical grade adhesive (e.g., an epoxy such as Loctite # 4981).
  • In one embodiment, the [0039] PVDF membrane 60 has a pore size ranging from 0.05 μm to 40 μm, preferably about 5 μm. The thickness of the filtration membrane 10 preferably may range from 10 μm to 500 μm, and even more preferably is about 100 μm. The diameter of the filtration membrane 10 preferably ranges from 0.1 to 3.0 cm in diameter, and even more preferably is about 0.7 cm.
  • In short, the filtration membrane is designed to promote neovascularization on the tissue interfacing side while preventing cellular passage with a bioprotective layer on the device side. As mentioned above, PEG is preferable but many materials with pore sizes too small for cells to pass through may be used. In addition, as mentioned above, photopolymerized PEG is suitable but other techniques of polymerization of the PEG are acceptable, for example, thermal or chemical methods may be used to initiate polymerization of the PEG. [0040]
  • Implant Housing [0041]
  • As depicted in FIG. 1E, the [0042] central housing 15 includes a conduit 70 with septa 20 contained within the conduit 70. The distal end of the conduit 75 is sealed with the filtration membrane 10. The portion of the conduit between the top of the filtration membrane 10 and the bottom of the lower septum 20 form the collection reservoir 25. The top of the conduit 70 contains a cap 80 to prevent debris and contaminants from entering the conduit 70 when the implant 1 is not in use. Although the cap depicted in FIG. 1E is a hinged, spring-loaded cap, numerous other cap designs may be used including, without limitation, a removable, snap-on or screw on cap.
  • The [0043] conduit 70 is preferably formed of stainless steel tubing or other rigid biocompatible material. Alternatively, the conduit may be formed integrally with the housing unit 15, being defined by the lumen thereof. The outer diameter of the housing element 15 may range from 0.1 to 2.0 cm, and is preferably about 0.7 cm. The lumen diameter of the housing element 15 may range from 0.125 to 1.775 cm, and is preferably about 0.5 cm. Each of the septum 20 is preferably constructed of a elastic, self-sealing biocompatible material, more preferably silicone rubber and is sized to fit snugly within the lumen of the conduit, thus providing a liquid-tight seal between the collection reservoir 25 and the upper portion of the conduit. The thickness of the individual septum 20 preferably may range from 0.05 to 1.0 cm and more preferably is about 0.3 cm. The distance between the bottom of the lower septum 20 and the filtration membrane 10 defines the depth of the collection reservoir 25 and preferably may range from 0.05 cm to 2.0 cm and more preferably is about 0.2 cm. The resulting volume of the collection reservoir 25 may range from 0.6 μl to 5.0 ml and more preferably is about 40 μl.
  • FIG. 2A illustrates an alternative embodiment of an implantable access port designed to be used for filtration of blood components. The implant includes a [0044] transcutaneous access component 85 with a central housing component 90 connected to an arterio-venous shunt 95. The distal end of the housing component 100 is secured to the wall of the arterio-venous shunt such that an appropriate filtration membrane 103 resides within the lumen of the arterio-venous shunt 105. Blood flowing through the arterio-venous shunt 95 is thereby filtered by the filtration membrane 103 and fluid is subsequently collected through the housing 90.
  • FIG. 2B illustrates a further embodiment of an implantable access port described above modified such that the [0045] filtration membrane 110 is shaped to increase the surface area and hence mass transport between the tissue space and collection reservoir of analytes in interstitial fluid, blood, or blood plasma.
  • FIG. 2C illustrates a further embodiment of the collection reservoir in which a [0046] safety stop 115 is incorporated to prevent the aspirating device such as needles or capillary tubes from damaging the filtration membrane and a coating of silver 120 is used to prevent bacterial accumulation in the collected fluid. As shown in FIG. 2C, the safety stop includes apertures along its circumference to permit analyte to pass in either direction between the reservoir and the aspirating device (or an agent delivery device). Preferably, the aspirating or delivery device having a side opening to the fluid intake or exhaust port to avoid blockage when the tip of the aspirating or delivery device contacts the bottom of the safety stop. In an alternative embodiment, apertures smaller than the tip of the aspirating or agent delivery device may be distributed throughout the surface of the safety stop, permitting a fluid intake or exhaust port to be located anywhere on the aspirating or agent delivery device, including on the bottom of its tip.
  • FIG. 2D is a cross-section of the implantable access port shown in FIG. 1A demonstrating alternative configurations for layers contained in the [0047] advanced filtration membrane 10. The advanced filtration membrane 10 may be composed of a discrete twolayer filtration membrane 140. In this configuration the PVDF membrane 60 is coated with a discrete layer of PEG membrane 65. Alternatively the advanced filtration membrane 10 may be composed of a partially embedded 2-layer filtration membrane 141 in which the PEG ultrafiltration membrane 65 partially penetrates a small distance into the PVDF membrane 60. In another alternative, the advanced filtration membrane 10 may be composed of a fully embedded 2-layer filtration membrane 142. In this configuration the full thickness of the PEG ultrafiltration membrane 65 is contained within a thickness of the PVDF membrane 60. In yet another alternative, the advanced filtration membrane 10 may be composed of a three layer filtration membrane 143. In this configuration a membrane support screen 64 is included to provide additional support to the filtration membrane 10. The membrane support screen may consist of any semi-rigid or rigid material but is preferably made using a stainless steel screen.
  • FIG. 2E is a cross-section of the implantable access port shown in FIG. 1A demonstrating alternative configurations for the [0048] housing 15 in which a replaceable septa insert 130 is incorporated. In this embodiment, the septa 20 are contained within a replaceable insert 130. The replaceable insert 130 may contain a threaded wall 135 such that once the septa 20 become worn to the point that they no longer self-seal, the user may unscrew the insert 130 and replace it with a new one. The new septa insert 130 is screwed into the threaded wall of the housing until it abuts a stop wall 131, thus allowing the inert 130 to be properly disposed within the lumen of the housing 15 (or conduit as shown in FIG. 1E). Other mechanisms for securing the replaceable insert may also be used including, without limitation, friction holds, mechanical catches and the like.
  • FIG. 2F is a cross-section of the [0049] housing 15 in which only a single self-sealing septum 20 is used. Any of the alternative embodiments may contain a single self-sealing septum 20 as opposed to the two-septum configuration as shown in FIG. 1B.
  • Turning to the operation of the preferred embodiment of the present invention, referring to FIG. 3A, the [0050] access port 1 is implanted so that the skirt 30 of the access component 5 is anchored in the subcutaneous tissue 200 and the neck 45 of the access component 5 penetrates the dermal 205 and epidermal layer 210 of the skin. After implantation, fibrous collagen begins to deposit in the holes 40 in the skirt 30 to help anchor the access component 5. The velour covering 55 provides a porous, fibrous-structure bed to encourage the growth of tissue and collagen around the skirt 30 to provide a biological seal with the epidermal cells which migrate and invaginate along the neck 50 until they reach the covering.
  • The [0051] housing component 15, which is fixed within the access component 5, provides for collection of fluid from the body without requiring breaking the skin barrier. The filtration membrane 10 attached to the housing 15 allows passage of interstitial fluid, blood, or blood plasma while preventing larger cells and proteins from entering the collection reservoir 25. The fluid filtered by the membrane and stored in the collection reservoir becomes the sample for analyte measurement using any applicable small volume sensor.
  • In the preferred embodiment, as shown in FIG. 3B, the [0052] access port 1 is designed to be used in conjunction with a sampling device 215. The sampling device 215 may be a needle or catheter, but is preferably a specially designed capillary tube 220 with an integral stop 225 such that it can not be introduced far enough to damage the filtration membrane 10. The sampling device 215 is passed through the self-sealing septa such that the distal end of the sampling device 230 is positioned within the collection reservoir 25 but does not come in contact with the filtration membrane 10. Fluid is drawn within a collection chamber of the sampling device 215 by capillary action or aspirating the proximal end of the sampling device 215 (e.g., by slideably withdrawing a plunger from the chamber of the sampling device 215).
  • Alternatively the implantable access port described herein may be used to deliver agents into the body. Such agents might include, but are not limited to, drugs, hormones, chemotherapeutic agents, photosensitizing agents, vaccines, radiological, or contrast agents. In operation, the agent to be administered would be placed within the collection reservoir [0053] 25 (now being used as a delivery reservoir) and the membrane 10 would be designed to allow passage of the agent into the subcutaneous fluid or blood space. Of particular interest, is the operation of the implantable access port to deliver insulin or for use in combination with insulin pumps.
  • The implantable access port described herein may be implanted anywhere on the body having a soft tissue layer sufficiently thick to accommodate the protrusion of the access port into the subdermal space. Preferably the implant is placed on the wrist or arm area for easy patient access and may include a device or implement to cover the port such as a wrist watch interface or skin colored bandage to improve patient acceptance of the aesthetic qualities of the device. Further, for durability, the access port is preferably placed somewhere on the body which is not subject to a lot of exposure or contact such as the abdomen. [0054]
  • As seen from the foregoing, the implantable access port provides a method for withdrawal of body fluids without requiring breach of the skin barrier. The implantable access port also provides for filtration of interstitial fluid, blood, or blood plasma resulting in a sample of fluid containing an analyte of interest. Because of its porosity and fibrous structure, the access port forms an infection-free, transcutaneous implant having a biological seal around the device. Therefore, the implant is suitable for long term use. Since the implant resides in the plane between the subcutaneous and dermal layers of tissue, subsequent removal is simple if necessary. Additionally, the access port has relatively few components and may be easily manufactured with common, readily available materials. Once implanted, the withdrawal of fluid from the body can be performed in a painless and reliable manner. [0055]
  • FIG. 4A illustrates a side view of an embodiment of an implanted access port which includes an [0056] external sampling stop 235 for providing safe access to the interstitial fluid without damaging the filtration membrane 10. As shown in FIG. 4B, the external sampling stop 235 permits a needle 217 to be used with the sampling device 215 in a safe manner. The sampling device 215 is inserted into the external sampling stop 235 until a flange at the forward end of the sampling device abuts a stop wall 237. As the sampling device 215 is inserted into the sampling stop 235, the needle 217 extends through an aperture in the stop wall 237, passes through the self-sealing septa 20 and comes to rest with the tip located just within the reservoir 25. The needle is preferably a non-coring needle (Part No. 7165, Popper & Sons, Inc., New Hyde Park, N.Y.) to prevent coring of the self-sealing septa 20. The sampling stop 235 can be custom designed according to the needle 217 and sampling device 210 used. In one embodiment, the sampling stop is removable, for example by unplugging or unscrewing from the implant 1, thus permitting sampling stops having various profiles and receptacle shapes to be used interchangeably. In an alternative embodiment, the sampling stop 235 forms part of the implant and is capped by an end cap as discussed above (see, for example, FIG. 1E, element 80).
  • FIG. 5A illustrates a side view of the implanted access port used in conjunction with an external analyte measurement device. In this embodiment an external [0057] analyte measurement device 240 is interfaced with the sampling device 215. This configuration allows for interstitial fluid withdrawn from the device and containing the analyte of interest to be directly communicated to an external analyte measurement device 240.
  • FIG. 5B illustrates a side view of an implanted access port that incorporates a replaceable electro-[0058] enzymatic sensor 245. In one embodiment, the sensor chemistry 260 is contained with the electroenzymatic sensor 245 and is placed within the reservoir 25 containing the interstitial fluid. Such a sensor chemistry is described in detail by Quinn et al. (Photo-crosslinked copolymers of 2 hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors), the entire content of which is hereby incorporated by reference. In the embodiment shown in FIG. 5B, a working electrode terminal 250 and a reference electrode terminal 255 are incorporated on the replaceable sensor 245 such that they are located outside the access port 1 with electrical conductors that are connected with the sensor chemistry 260. By this arrangement, an external analyte measurement device 240 may be interfaced with the replaceable sensor 245 to provide a measurement of the analyte of interest. FIG. 5C illustrates a close up side view of the replaceable sensor 245. The sensor 245 may also contain a fluid withdrawal port 252 that would allow the user to withdraw interstitial fluid periodically in order to calibrate the electroenzymatic sensor 245. Alternatively, the sensor 245 can be removed from the access port 1 and calibrated in known standards.
  • FIG. 5D illustrates the implantable access port and replaceable electroenzymatic sensor of FIG. 5B used in conjunction with a wristwatch style measurement display device. In this embodiment, a wristwatch style analyte [0059] measurement display device 265 may be continuously worn over the access port 1 and replaceable sensor 245 to display continuous measurement of the analyte of interest. Numerous other styles and configurations of measurement display devices may be worn over the access port in alternative embodiments.
  • While the present invention has been described with reference to illustrative embodiments that include specific details, such embodiments and details should not be construed as limiting the scope of the invention. For example, though numerous preferences for shapes, materials, sizes and configurations have been described, other shapes, materials, sizes and configurations may be used without departing from the spirit and scope of the present invention. Those having ordinary skill in the art and access to the teachings provided herein will recognize additional modifications, applications, and embodiments within the scope the invention described herein and additional fields in which the invention would be of significant utility without undue experimentation. Thus the scope of the invention should be determined by the appended claims and their legal equivalents, rather than by the examples given. [0060]

Claims (58)

What is claimed is:
1. An transcutaneous implant comprising:
an access component to provide a stable dermal interface;
a central housing disposed within the access component, the central housing having a first end for external access and a second end;
a first septum disposed within the central housing; and
a filtration membrane disposed at the second end of the central housing to promote neovascularization and transfer of analyte in bodily fluid into a reservoir formed by the filtration membrane, the first septum and the central housing.
2. The implant of claim 1 wherein the access component includes a neck having a first end and a second end, and skirt that extends outwardly from the second end of the neck to anchor the access component in subcutaneous tissue.
3. The implant of claim 2 wherein the central housing is formed integrally with the access component and is defined by an inner surface of the neck.
4. The implant of claim 2 wherein the central housing extends beneath the skirt of the access component and is adapted to be secured to a wall of an arterio-venous shunt such that the filtration membrane resides within the arterio-venous shunt.
5. The implant of claim 2 wherein the access component is covered by a porous covering of material that encourages cell infiltration and formation of subcutaneous tissue and collagen.
6. The implant of claim 5 wherein the porous covering of material includes polyester velour.
7. The implant of claim 2 wherein the skirt and neck are integrally formed of a flexible, biocompatible material.
8. The implant of claim 7 wherein the flexible biocompatible material is a member of a group of materials that includes flexible medical grade polyurethane, polymethyl methacrylate (PMMA), polyethylene (PE), polyvinyl chloride (PVC), polycarbonate, polypropylene (PP) polydimethyl siloxane (PDMS), ethylene glycol dimethacrylate (EGDM), polytetrafluoroethylene PTFE), and nylon.
9. The implant of claim 2 wherein the skirt includes holes in which deposition of fibrous collagen after implantation helps to anchor the access component.
10. The implant of claim 1 wherein the filtration membrane includes a material that allows passive diffusion of the analyte in the bodily fluid, but substantially prevents transport of cells and larger proteins.
11. The implant of claim 1 wherein the filtration membrane includes first material to promote neovascularization.
12. The implant of claim 11 wherein the first material includes polyvinylidene fluoride (PVDF).
13. The implant of claim 11 wherein the filtration membrane further includes a second material which allows passive diffusion of the analyte in the bodily fluid, but substantially prevents transport of cells and larger proteins.
14. The implant of claim 13 wherein the second material includes polymerized polyethylene glycol (PEG).
15. The implant of claim 13 wherein the second material is laminated on the first material to form a discrete two-layer filtration membrane.
16. The implant of claim 13 wherein a portion of the second material penetrates into the first material to form a partially embedded two-layer filtration membrane.
17. The implant of claim 13 wherein the second material is contained within a layer of the first material to form a fully embedded two-layer filtration membrane.
18. The implant of claim 13 wherein the filtration membrane further includes a third material more rigid than at least one of the first material and the second material to provide mechanical support to the filtration membrane.
19. The implant of claim 11 wherein the first material has a pore size ranging from 0.05 μm to 40 μm.
20. The implant of claim 1 wherein the first septum forms a liquid-tight seal between the reservoir and a side of the first septum nearest the first end of the central housing.
21. The implant of claim 20 wherein the first septum is formed of a self-sealing material such that, after the first septum has been penetrated by a fluid sampling/delivery device and the fluid sampling/delivery device removed, the first septum self-seals to re-establish the liquid-tight seal.
22. The implant of claim 21 wherein the first septum is formed from a material that includes silicone rubber.
23. The implant of claim 1 wherein the central housing includes a conduit disposed within the lumen of the central housing and wherein the first septum is disposed within the conduit and the filtration membrane is disposed at an end of the conduit adjacent the second end of the central housing.
24. The implant of claim 23 wherein the conduit is formed integrally with the central housing, the conduit being defined by an inner surface of the central housing.
25. The implant of claim 23 wherein the conduit is formed of a rigid biocompatible material.
26. The implant of claim 23 further comprising a cap disposed over an end of the conduit adjacent the first end of the central housing.
27. The implant of claim 23 further comprising a second septum disposed within the conduit nearer the first end of the central housing than the first septum, the first and second septa defining a chamber within the conduit.
28. The implant of claim 23 further comprising a support member disposed within the conduit to support the first septum, the first septum being disposed within the conduit adjacent the support member.
29. The implant of claim 1 further comprising a cap disposed over the first end of the central housing.
30. The implant of claim 1 further comprising a second septum disposed within the central housing nearer the first end than the first septum, the first and second septa defining a chamber within the central housing.
31. The implant of claim 30 wherein the second septum forms a liquid-tight seal between the chamber and a side of the second septum nearest the first end of the central housing.
32. The implant of claim 1 wherein the filtration membrane is attached to the central housing using a medical grade adhesive.
33. The implant of claim 1 wherein the filtration membrane extends outwardly to form a filtration surface area that exceeds an area of a cross section of the second end of the central housing.
34. The implant of claim 1 further comprising a safety stop to prevent a fluid sampling/delivery device from contacting the filtration membrane.
35. The implant of claim 34 wherein the safety stop is disposed within the reservoir, the safety stop including an aperture to permit the analyte to pass between the reservoir and the fluid sampling/delivery device.
36. The implant of claim 1 wherein the reservoir is lined with an antibacterial coating.
37. The implant of claim 36 wherein the antibacterial coating includes silver.
38. The implant of claim 1 wherein the first septum is removable from the central housing to allow replacement thereof.
39. The implant of claim 1 further comprising a sampling stop disposed at the first end of the central housing to limit the insertion of a fluid sampling/delivery device such that the device is prevented from contacting the filtration membrane.
40. The implant of claim 39 wherein the sampling stop includes a stop wall adapted to engage a flange of the fluid sampling/delivery device, the stop wall including an aperture to receive a narrower portion of the fluid sampling/delivery device such that a tip of the narrower portion of the fluid sampling/delivery device rests within the reservoir when the flange of the fluid sampling/delivery device engages the stop wall.
41. The implant of claim 39 wherein the sampling stop is removable from the implant.
42. The implant of claim 1 wherein the central housing is adapted to engage an analyte measurement device and fluid sampling device such that the analyte in the reservoir is communicated to the analyte measurement device via the fluid sampling device and measured by the analyte measurement device while the analyte measurement device and fluid sampling device are engaged by the central housing.
43. A sensing system having a transcutaneous implant device comprising:
an electroenzymatic sensor;
a transcutaneous implant device, including:
an access component to provide a stable dermal interface;
a central housing disposed within the access component, the central housing having a first end for external access and a second end;
a first septum disposed within the central housing; and
a filtration membrane disposed at the second end of the central housing to promote neovascularization and transfer of analyte in bodily fluid into a reservoir formed by the filtration membrane, the first septum and the central housing.
44. The sensing system of claim 43 wherein the electroenzymatic sensor includes a chemical sensor disposed within the reservoir and first and second terminals disposed adjacent the first end of the central housing and coupled to the chemical sensor via respective electrical conductors.
45. The sensing system of claim 43 wherein the electroenzymatic sensor further includes a fluid withdrawal port to allow periodic withdrawal of the analyte.
46. The sensing system of claim 43 wherein the electroenzymatic sensor is removable.
47. The sensing system of claim 43 further comprising a display device coupled adjacent the first end of the central housing, the display device cooperating with the electroenzymatic sensor to display a measure of the analyte.
48. The sensing system of claim 47 wherein the display device is a wristwatch style device.
49. An apparatus for safely withdrawing bodily fluid from a transcutaneous implant, the apparatus comprising:
a projecting portion adapted to extend through a septum of the transcutaneous implant and into a collection reservoir of the implant; and
a flange adapted to engage a stop wall of the transcutaneous implant such that the projecting portion of the apparatus is prevented from contacting a filtration membrane of the transcutaneous implant.
50. The apparatus of claim 49 wherein the projecting portion includes a non-coring needle.
51. The apparatus of claim 49 further comprising:
a chamber; and
an aspirator to draw the bodily fluid from the collection reservoir into the chamber.
52. The apparatus of claim 51 wherein the aspirator is a plunger slideably disposed within the chamber and wherein the bodily fluid is drawn from the collection reservoir into the chamber when the plunger is slideably withdrawn from the chamber.
53. An apparatus for safely withdrawing bodily fluid from a transcutaneous implant, the apparatus comprising:
a chamber;
an aspirator operable to create suction pressure within the chamber; and
a projecting portion adapted to extend through a septum of the transcutaneous implant and into a collection reservoir of the transcutaneous implant, the projecting portion including a tip having an aperture, and a passage extending between the chamber and the aperture, the tip of the projecting portion being configured to engage a safety stop disposed within the collection reservoir of the transcutaneous implant such that tip of the aperture is prevented from contacting a filtration membrane of the transcutaneous implant and such that the aperture is unblocked and able to receive the bodily fluid when the aspirator is operated to create suction pressure within the chamber.
54. The apparatus of claim 53 wherein the projecting portion is configured to prevent coring of the septum when extended there through.
55. A septum for forming a liquid-tight seal within a lumen of a transcutaneous implant, the septum comprising:
an outer surface for engaging the lumen of the transcutaneous implant; and
a first self-sealing aperture disposed within the outer surface.
56. The septum of claim 55 wherein the outer surface for engaging the lumen of the transcutaneous implant includes threads to screwably insert the septum into the lumen of the transcutaneous implant.
57. The septum of claim 55 further comprising a second self-sealing aperture disposed within the outer surface, the first and second self-sealing apertures being positioned at respective ends of the septum.
58. The septum of claim 55 wherein the septum further comprises a stop surface to engage a stop wall of the lumen of the transcutaneous implant to establish appropriate disposition of the septum within the lumen.
US10/209,819 2000-05-22 2002-07-31 Apparatus for access to interstitial fluid, blood, or blood plasma components Abandoned US20020183604A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/209,819 US20020183604A1 (en) 2000-05-22 2002-07-31 Apparatus for access to interstitial fluid, blood, or blood plasma components

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/575,591 US6459917B1 (en) 2000-05-22 2000-05-22 Apparatus for access to interstitial fluid, blood, or blood plasma components
US10/209,819 US20020183604A1 (en) 2000-05-22 2002-07-31 Apparatus for access to interstitial fluid, blood, or blood plasma components

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/575,591 Division US6459917B1 (en) 2000-05-22 2000-05-22 Apparatus for access to interstitial fluid, blood, or blood plasma components

Publications (1)

Publication Number Publication Date
US20020183604A1 true US20020183604A1 (en) 2002-12-05

Family

ID=24300921

Family Applications (2)

Application Number Title Priority Date Filing Date
US09/575,591 Expired - Fee Related US6459917B1 (en) 2000-05-22 2000-05-22 Apparatus for access to interstitial fluid, blood, or blood plasma components
US10/209,819 Abandoned US20020183604A1 (en) 2000-05-22 2002-07-31 Apparatus for access to interstitial fluid, blood, or blood plasma components

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/575,591 Expired - Fee Related US6459917B1 (en) 2000-05-22 2000-05-22 Apparatus for access to interstitial fluid, blood, or blood plasma components

Country Status (1)

Country Link
US (2) US6459917B1 (en)

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050240155A1 (en) * 2004-04-27 2005-10-27 Conlon Sean P Surgically implantable injection port having a centered catheter connection tube
US20060094945A1 (en) * 2004-10-28 2006-05-04 Sontra Medical Corporation System and method for analyte sampling and analysis
US20100076284A1 (en) * 2007-06-21 2010-03-25 Abbott Diabetes Care Inc. Health Management Devices and Methods
US7727147B1 (en) * 2004-05-14 2010-06-01 Flint Hills Scientific Llc Method and system for implantable glucose monitoring and control of a glycemic state of a subject
US20110098525A1 (en) * 2009-10-26 2011-04-28 Kermode James R Ventricular volume reduction
US20110178362A1 (en) * 2006-02-06 2011-07-21 Evans Michael A Systems and methods for volume reduction
US7985199B2 (en) * 2005-03-17 2011-07-26 Unomedical A/S Gateway system
US8064977B2 (en) * 2002-05-22 2011-11-22 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US8165651B2 (en) * 2004-02-09 2012-04-24 Abbott Diabetes Care Inc. Analyte sensor, and associated system and method employing a catalytic agent
US8219175B2 (en) 2003-10-31 2012-07-10 Abbott Diabetes Care Inc. Method of calibrating an analyte-measurement device, and associated methods, devices and systems
US8506482B2 (en) 2006-02-28 2013-08-13 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US8617069B2 (en) 2007-06-21 2013-12-31 Abbott Diabetes Care Inc. Health monitor
US8657873B2 (en) 1999-08-09 2014-02-25 Cardiokinetix, Inc. System for improving cardiac function
US8672827B2 (en) 1999-08-09 2014-03-18 Cardiokinetix, Inc. Cardiac device and methods of use thereof
US8827892B2 (en) 2002-08-01 2014-09-09 Cardiokinetix, Inc. Therapeutic methods and devices following myocardial infarction
EP2859911A1 (en) * 2013-10-11 2015-04-15 qSTAR Medical SAS Vascular access port devices with incorporated sensors
US9017394B2 (en) 1999-08-09 2015-04-28 Cardiokinetix, Inc. Retrievable cardiac devices
US9069536B2 (en) 2011-10-31 2015-06-30 Abbott Diabetes Care Inc. Electronic devices having integrated reset systems and methods thereof
US9078660B2 (en) 2000-08-09 2015-07-14 Cardiokinetix, Inc. Devices and methods for delivering an endocardial device
US9332992B2 (en) 2004-08-05 2016-05-10 Cardiokinetix, Inc. Method for making a laminar ventricular partitioning device
US9332993B2 (en) 2004-08-05 2016-05-10 Cardiokinetix, Inc. Devices and methods for delivering an endocardial device
US9532737B2 (en) 2011-02-28 2017-01-03 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US9694121B2 (en) 1999-08-09 2017-07-04 Cardiokinetix, Inc. Systems and methods for improving cardiac function
EP3243549A1 (en) * 2016-05-12 2017-11-15 Renishaw plc Percutaneous access apparatus
US10064696B2 (en) 2000-08-09 2018-09-04 Edwards Lifesciences Corporation Devices and methods for delivering an endocardial device
US10136816B2 (en) 2009-08-31 2018-11-27 Abbott Diabetes Care Inc. Medical devices and methods
US10307147B2 (en) 1999-08-09 2019-06-04 Edwards Lifesciences Corporation System for improving cardiac function by sealing a partitioning membrane within a ventricle
US10307253B2 (en) 1999-08-09 2019-06-04 Edwards Lifesciences Corporation System for improving cardiac function by sealing a partitioning membrane within a ventricle
US20190308004A1 (en) * 2018-04-04 2019-10-10 Marius Saines Low profile self-sealing access port
US10617823B2 (en) 2007-02-15 2020-04-14 Abbott Diabetes Care Inc. Device and method for automatic data acquisition and/or detection
US10751183B2 (en) 2014-09-28 2020-08-25 Edwards Lifesciences Corporation Apparatuses for treating cardiac dysfunction
US10898330B2 (en) 2017-03-28 2021-01-26 Edwards Lifesciences Corporation Positioning, deploying, and retrieving implantable devices
US11006871B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11229382B2 (en) 2013-12-31 2022-01-25 Abbott Diabetes Care Inc. Self-powered analyte sensor and devices using the same
US11793936B2 (en) 2009-05-29 2023-10-24 Abbott Diabetes Care Inc. Medical device antenna systems having external antenna configurations

Families Citing this family (126)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7899511B2 (en) 2004-07-13 2011-03-01 Dexcom, Inc. Low oxygen in vivo analyte sensor
US7192450B2 (en) 2003-05-21 2007-03-20 Dexcom, Inc. Porous membranes for use with implantable devices
US20050033132A1 (en) 1997-03-04 2005-02-10 Shults Mark C. Analyte measuring device
US6001067A (en) 1997-03-04 1999-12-14 Shults; Mark C. Device and method for determining analyte levels
US9155496B2 (en) 1997-03-04 2015-10-13 Dexcom, Inc. Low oxygen in vivo analyte sensor
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066695B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6949816B2 (en) 2003-04-21 2005-09-27 Motorola, Inc. Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
DE19822711B4 (en) * 1998-05-20 2006-11-23 Disetronic Licensing Ag Sensor system with port body
US7247138B2 (en) * 1999-07-01 2007-07-24 Medtronic Minimed, Inc. Reusable analyte sensor site and method of using the same
JP2003508734A (en) * 1999-08-31 2003-03-04 シーエムイー テレメトリックス インク. Apparatus for verifying the accuracy of a spectrum analyzer
DE19942898B4 (en) * 1999-09-08 2007-07-05 Disetronic Licensing Ag dialysis probe
US6560471B1 (en) 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
US7041468B2 (en) 2001-04-02 2006-05-09 Therasense, Inc. Blood glucose tracking apparatus and methods
US7209783B2 (en) * 2001-06-15 2007-04-24 Cardiac Pacemakers, Inc. Ablation stent for treating atrial fibrillation
US7044911B2 (en) * 2001-06-29 2006-05-16 Philometron, Inc. Gateway platform for biological monitoring and delivery of therapeutic compounds
US6702857B2 (en) 2001-07-27 2004-03-09 Dexcom, Inc. Membrane for use with implantable devices
US20030032874A1 (en) 2001-07-27 2003-02-13 Dexcom, Inc. Sensor head for use with implantable devices
DE10142637B4 (en) * 2001-08-31 2009-07-09 Disetronic Licensing Ag Transcutaneous implant with surface structure and method for producing such an implant
US8364229B2 (en) 2003-07-25 2013-01-29 Dexcom, Inc. Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
US7236821B2 (en) 2002-02-19 2007-06-26 Cardiac Pacemakers, Inc. Chronically-implanted device for sensing and therapy
US7226978B2 (en) 2002-05-22 2007-06-05 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US7072711B2 (en) 2002-11-12 2006-07-04 Cardiac Pacemakers, Inc. Implantable device for delivering cardiac drug therapy
US7134999B2 (en) 2003-04-04 2006-11-14 Dexcom, Inc. Optimized sensor geometry for an implantable glucose sensor
US7875293B2 (en) 2003-05-21 2011-01-25 Dexcom, Inc. Biointerface membranes incorporating bioactive agents
WO2005012873A2 (en) 2003-07-25 2005-02-10 Dexcom, Inc. Electrode systems for electrochemical sensors
US9763609B2 (en) 2003-07-25 2017-09-19 Dexcom, Inc. Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
US7761130B2 (en) 2003-07-25 2010-07-20 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8060173B2 (en) 2003-08-01 2011-11-15 Dexcom, Inc. System and methods for processing analyte sensor data
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US7774145B2 (en) 2003-08-01 2010-08-10 Dexcom, Inc. Transcutaneous analyte sensor
US8275437B2 (en) 2003-08-01 2012-09-25 Dexcom, Inc. Transcutaneous analyte sensor
US7494465B2 (en) 2004-07-13 2009-02-24 Dexcom, Inc. Transcutaneous analyte sensor
US20100168543A1 (en) 2003-08-01 2010-07-01 Dexcom, Inc. System and methods for processing analyte sensor data
US7591801B2 (en) 2004-02-26 2009-09-22 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US20190357827A1 (en) 2003-08-01 2019-11-28 Dexcom, Inc. Analyte sensor
US7320675B2 (en) 2003-08-21 2008-01-22 Cardiac Pacemakers, Inc. Method and apparatus for modulating cellular metabolism during post-ischemia or heart failure
US7920906B2 (en) 2005-03-10 2011-04-05 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US9247900B2 (en) 2004-07-13 2016-02-02 Dexcom, Inc. Analyte sensor
US11633133B2 (en) 2003-12-05 2023-04-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8287453B2 (en) 2003-12-05 2012-10-16 Dexcom, Inc. Analyte sensor
US8423114B2 (en) 2006-10-04 2013-04-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8364231B2 (en) 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
EP2239567B1 (en) 2003-12-05 2015-09-02 DexCom, Inc. Calibration techniques for a continuous analyte sensor
US8774886B2 (en) 2006-10-04 2014-07-08 Dexcom, Inc. Analyte sensor
US7364592B2 (en) * 2004-02-12 2008-04-29 Dexcom, Inc. Biointerface membrane with macro-and micro-architecture
US20050194303A1 (en) * 2004-03-02 2005-09-08 Sniegowski Jeffry J. MEMS flow module with filtration and pressure regulation capabilities
US8808228B2 (en) 2004-02-26 2014-08-19 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US7840263B2 (en) 2004-02-27 2010-11-23 Cardiac Pacemakers, Inc. Method and apparatus for device controlled gene expression
US8792955B2 (en) 2004-05-03 2014-07-29 Dexcom, Inc. Transcutaneous analyte sensor
US7764995B2 (en) 2004-06-07 2010-07-27 Cardiac Pacemakers, Inc. Method and apparatus to modulate cellular regeneration post myocardial infarct
US7783333B2 (en) 2004-07-13 2010-08-24 Dexcom, Inc. Transcutaneous medical device with variable stiffness
US8565848B2 (en) 2004-07-13 2013-10-22 Dexcom, Inc. Transcutaneous analyte sensor
US7857760B2 (en) 2004-07-13 2010-12-28 Dexcom, Inc. Analyte sensor
US7310544B2 (en) 2004-07-13 2007-12-18 Dexcom, Inc. Methods and systems for inserting a transcutaneous analyte sensor
US8452368B2 (en) 2004-07-13 2013-05-28 Dexcom, Inc. Transcutaneous analyte sensor
US20060270922A1 (en) 2004-07-13 2006-11-30 Brauker James H Analyte sensor
US20060030790A1 (en) * 2004-08-06 2006-02-09 Braig James R Sample element with barrier material and vacuum
US7828711B2 (en) 2004-08-16 2010-11-09 Cardiac Pacemakers, Inc. Method and apparatus for modulating cellular growth and regeneration using ventricular assist device
US20060041318A1 (en) * 2004-08-19 2006-02-23 Shannon Donald T Laminar skin-bone fixation transcutaneous implant and method for use thereof
US7567841B2 (en) 2004-08-20 2009-07-28 Cardiac Pacemakers, Inc. Method and apparatus for delivering combined electrical and drug therapies
US7981065B2 (en) 2004-12-20 2011-07-19 Cardiac Pacemakers, Inc. Lead electrode incorporating extracellular matrix
US8060219B2 (en) 2004-12-20 2011-11-15 Cardiac Pacemakers, Inc. Epicardial patch including isolated extracellular matrix with pacing electrodes
US8346346B1 (en) 2005-01-24 2013-01-01 The Board Of Trustees Of The Leland Stanford Junior University Optical analysis system and approach therefor
US8133178B2 (en) 2006-02-22 2012-03-13 Dexcom, Inc. Analyte sensor
US20090076360A1 (en) 2007-09-13 2009-03-19 Dexcom, Inc. Transcutaneous analyte sensor
US7665424B2 (en) * 2005-07-06 2010-02-23 Strategic Applications, Inc. Harness interface conduit, tether line, and swivel for use in animals
US7616990B2 (en) 2005-10-24 2009-11-10 Cardiac Pacemakers, Inc. Implantable and rechargeable neural stimulator
US9757061B2 (en) 2006-01-17 2017-09-12 Dexcom, Inc. Low oxygen in vivo analyte sensor
US20080071158A1 (en) 2006-06-07 2008-03-20 Abbott Diabetes Care, Inc. Analyte monitoring system and method
US7831287B2 (en) 2006-10-04 2010-11-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US20200037875A1 (en) 2007-05-18 2020-02-06 Dexcom, Inc. Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
EP2152350A4 (en) 2007-06-08 2013-03-27 Dexcom Inc Integrated medicament delivery device for use with continuous analyte sensor
EP2227132B1 (en) 2007-10-09 2023-03-08 DexCom, Inc. Integrated insulin delivery system with continuous glucose sensor
US8417312B2 (en) 2007-10-25 2013-04-09 Dexcom, Inc. Systems and methods for processing sensor data
US9440058B2 (en) * 2007-12-17 2016-09-13 Cook Medical Technologies, LLC Device for enabling repeated access to a vessel
WO2009096855A1 (en) * 2008-01-28 2009-08-06 Milux Holding Sa Blood clot removal device, system, and method
WO2009105432A2 (en) * 2008-02-19 2009-08-27 Portaero, Inc. Devices and methods for delivery of a therapeutic agent through a pneumostoma
US8396528B2 (en) 2008-03-25 2013-03-12 Dexcom, Inc. Analyte sensor
US8583204B2 (en) 2008-03-28 2013-11-12 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8682408B2 (en) 2008-03-28 2014-03-25 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
WO2009129474A1 (en) 2008-04-17 2009-10-22 Allergan, Inc. Implantable access port device and attachment system
US9023063B2 (en) 2008-04-17 2015-05-05 Apollo Endosurgery, Inc. Implantable access port device having a safety cap
KR20100139144A (en) 2008-04-21 2010-12-31 카를 프레데릭 에드만 Metabolic energy monitoring system
WO2009145920A1 (en) * 2008-05-30 2009-12-03 Intuity Medical, Inc. Body fluid sampling device -- sampling site interface
EP2467149B1 (en) * 2009-08-17 2018-04-04 Ashok K. Singh Fluid from skin and omentum for medical use
US8506532B2 (en) 2009-08-26 2013-08-13 Allergan, Inc. System including access port and applicator tool
US8715158B2 (en) 2009-08-26 2014-05-06 Apollo Endosurgery, Inc. Implantable bottom exit port
US8708979B2 (en) 2009-08-26 2014-04-29 Apollo Endosurgery, Inc. Implantable coupling device
CN102711607B (en) * 2009-11-16 2016-05-04 马奎特急救护理股份公司 Gravity flow mensuration system
US8882728B2 (en) 2010-02-10 2014-11-11 Apollo Endosurgery, Inc. Implantable injection port
WO2011112972A2 (en) 2010-03-11 2011-09-15 Philometron, Inc. Physiological monitor system for determining medication delivery and outcome
US20110270021A1 (en) 2010-04-30 2011-11-03 Allergan, Inc. Electronically enhanced access port for a fluid filled implant
US20110270025A1 (en) 2010-04-30 2011-11-03 Allergan, Inc. Remotely powered remotely adjustable gastric band system
US8992415B2 (en) 2010-04-30 2015-03-31 Apollo Endosurgery, Inc. Implantable device to protect tubing from puncture
EP2384699B1 (en) * 2010-05-06 2012-12-12 Roche Diagnostics GmbH Lancet cartridge and method for its production
JP4815024B1 (en) * 2010-07-02 2011-11-16 日機装株式会社 Artificial blood vessels and artificial blood vessel access ports
US20120041258A1 (en) 2010-08-16 2012-02-16 Allergan, Inc. Implantable access port system
US9737660B2 (en) 2010-08-25 2017-08-22 Medtronic, Inc. Drug infusion device with controllable valve
US10143796B2 (en) 2010-08-25 2018-12-04 Medtronic, Inc. Fluid delivery device refill access
US20120065460A1 (en) 2010-09-14 2012-03-15 Greg Nitka Implantable access port system
WO2012142502A2 (en) 2011-04-15 2012-10-18 Dexcom Inc. Advanced analyte sensor calibration and error detection
US8821373B2 (en) 2011-05-10 2014-09-02 Apollo Endosurgery, Inc. Directionless (orientation independent) needle injection port
US9615759B2 (en) * 2011-07-12 2017-04-11 Bard Access Systems, Inc. Devices and methods for ECG guided vascular access
US8801597B2 (en) 2011-08-25 2014-08-12 Apollo Endosurgery, Inc. Implantable access port with mesh attachment rivets
US9199069B2 (en) 2011-10-20 2015-12-01 Apollo Endosurgery, Inc. Implantable injection port
US8858421B2 (en) 2011-11-15 2014-10-14 Apollo Endosurgery, Inc. Interior needle stick guard stems for tubes
US9089395B2 (en) 2011-11-16 2015-07-28 Appolo Endosurgery, Inc. Pre-loaded septum for use with an access port
US20150297873A1 (en) * 2012-08-22 2015-10-22 Clemson University Research Foundation Percutaneous tube stabilization device
US11420033B2 (en) 2013-01-23 2022-08-23 C. R. Bard, Inc. Low-profile single and dual vascular access device
US11464960B2 (en) 2013-01-23 2022-10-11 C. R. Bard, Inc. Low-profile single and dual vascular access device
EP3342391A1 (en) 2013-01-23 2018-07-04 C.R. Bard Inc. Low-profile access port
JP2015175837A (en) * 2014-03-18 2015-10-05 ソニー株式会社 Plate-like member for pipette tips, pipette tip, liquid agitation kit and liquid agitation apparatus
EP3128932A4 (en) * 2014-04-10 2017-11-29 University Health Network Cannula for connecting medical devices to biological systems
US9814413B2 (en) * 2014-07-24 2017-11-14 Thomas Jefferson University Long-term implantable monitoring system and methods of use
USD870264S1 (en) 2017-09-06 2019-12-17 C. R. Bard, Inc. Implantable apheresis port
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
CA3077720A1 (en) 2017-10-24 2019-05-02 Dexcom, Inc. Pre-connected analyte sensors
EP3749176A1 (en) * 2018-02-09 2020-12-16 W.L. Gore & Associates, Inc. Implantable access chamber and associated methods of use
EP3760273A1 (en) * 2019-07-02 2021-01-06 SeraIP AG Implantable skin penetration device

Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3638649A (en) * 1969-07-07 1972-02-01 Univ Minnesota Implantable prosthetic pass-through device
US3683965A (en) * 1970-04-08 1972-08-15 Materials Technology Corp Adjustable choke valve
US3783868A (en) * 1971-05-06 1974-01-08 Gulf Oil Corp Percutaneous implant
US3991756A (en) * 1975-08-18 1976-11-16 Donald Synder Method and apparatus for intravenous access
US4402694A (en) * 1981-07-16 1983-09-06 Biotek, Inc. Body cavity access device containing a hormone source
US4633878A (en) * 1983-04-18 1987-01-06 Guiseppe Bombardieri Device for the automatic insulin or glucose infusion in diabetic subjects, based on the continuous monitoring of the patient's glucose, obtained without blood withdrawal
US4777953A (en) * 1987-02-25 1988-10-18 Ash Medical Systems, Inc. Capillary filtration and collection method for long-term monitoring of blood constituents
US4810246A (en) * 1987-11-04 1989-03-07 L. Vad Technology, Inc. Disposable cell culture chamber with remote access
US4854322A (en) * 1987-02-25 1989-08-08 Ash Medical Systems, Inc. Capillary filtration and collection device for long-term monitoring of blood constituents
US4886501A (en) * 1987-08-25 1989-12-12 Shiley Infusaid Inc. Implantable device
US4886502A (en) * 1986-12-09 1989-12-12 Thermedics, Inc. Peritoneal access catheter
US4955861A (en) * 1988-04-21 1990-09-11 Therex Corp. Dual access infusion and monitoring system
US5001054A (en) * 1986-06-26 1991-03-19 Becton, Dickinson And Company Method for monitoring glucose
US5035711A (en) * 1983-03-24 1991-07-30 Kabushiki Kaisya Advance Kaihatsu Kenkyujo Transcutaneously implantable element
US5161532A (en) * 1990-04-19 1992-11-10 Teknekron Sensor Development Corporation Integral interstitial fluid sensor
US5242415A (en) * 1992-08-14 1993-09-07 L-Vad Technology, Inc. Percutaneous access device
US5582184A (en) * 1993-10-13 1996-12-10 Integ Incorporated Interstitial fluid collection and constituent measurement
US5588808A (en) * 1994-12-08 1996-12-31 Hytech Pumps International, Inc. Pump pressure multiplier
US5617851A (en) * 1992-10-14 1997-04-08 Endodermic Medical Technologies Company Ultrasonic transdermal system for withdrawing fluid from an organism and determining the concentration of a substance in the fluid
US5662616A (en) * 1995-07-07 1997-09-02 Bousquet; Gerald G. Transcutaneous access device
US5706607A (en) * 1994-09-17 1998-01-13 Frey; Harry Magnetic door seal
US5722397A (en) * 1993-11-15 1998-03-03 Altea Technologies, Inc. Enhancement of transdermal monitoring applications with ultrasound and chemical enhancers
US5833655A (en) * 1997-05-15 1998-11-10 L. Vad Technology, Inc. Percutaneous access device having removable turret assembly
US5885211A (en) * 1993-11-15 1999-03-23 Spectrix, Inc. Microporation of human skin for monitoring the concentration of an analyte
US5913833A (en) * 1997-02-07 1999-06-22 Abbott Laboratories Method and apparatus for obtaining biological fluids
US5964804A (en) * 1990-10-31 1999-10-12 Baxter International Inc. Close vascularization implant material
US6099508A (en) * 1995-07-07 2000-08-08 Bousquet; Gerald G. Transcutaneous access device
US6122536A (en) * 1995-07-06 2000-09-19 Animas Corporation Implantable sensor and system for measurement and control of blood constituent levels

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3663965A (en) 1970-06-08 1972-05-23 Henry L Lee Jr Bacteria-resistant percutaneous conduit device
US5271736A (en) 1991-05-13 1993-12-21 Applied Medical Research Collagen disruptive morphology for implants
US5568806A (en) 1995-02-16 1996-10-29 Minimed Inc. Transcutaneous sensor insertion set

Patent Citations (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3638649A (en) * 1969-07-07 1972-02-01 Univ Minnesota Implantable prosthetic pass-through device
US3683965A (en) * 1970-04-08 1972-08-15 Materials Technology Corp Adjustable choke valve
US3783868A (en) * 1971-05-06 1974-01-08 Gulf Oil Corp Percutaneous implant
US3991756A (en) * 1975-08-18 1976-11-16 Donald Synder Method and apparatus for intravenous access
US4402694A (en) * 1981-07-16 1983-09-06 Biotek, Inc. Body cavity access device containing a hormone source
US5035711A (en) * 1983-03-24 1991-07-30 Kabushiki Kaisya Advance Kaihatsu Kenkyujo Transcutaneously implantable element
US4633878A (en) * 1983-04-18 1987-01-06 Guiseppe Bombardieri Device for the automatic insulin or glucose infusion in diabetic subjects, based on the continuous monitoring of the patient's glucose, obtained without blood withdrawal
US5001054A (en) * 1986-06-26 1991-03-19 Becton, Dickinson And Company Method for monitoring glucose
US4886502A (en) * 1986-12-09 1989-12-12 Thermedics, Inc. Peritoneal access catheter
US4777953A (en) * 1987-02-25 1988-10-18 Ash Medical Systems, Inc. Capillary filtration and collection method for long-term monitoring of blood constituents
US4854322A (en) * 1987-02-25 1989-08-08 Ash Medical Systems, Inc. Capillary filtration and collection device for long-term monitoring of blood constituents
US4886501A (en) * 1987-08-25 1989-12-12 Shiley Infusaid Inc. Implantable device
US4810246A (en) * 1987-11-04 1989-03-07 L. Vad Technology, Inc. Disposable cell culture chamber with remote access
US4955861A (en) * 1988-04-21 1990-09-11 Therex Corp. Dual access infusion and monitoring system
US5161532A (en) * 1990-04-19 1992-11-10 Teknekron Sensor Development Corporation Integral interstitial fluid sensor
US5964804A (en) * 1990-10-31 1999-10-12 Baxter International Inc. Close vascularization implant material
US5242415A (en) * 1992-08-14 1993-09-07 L-Vad Technology, Inc. Percutaneous access device
US5617851A (en) * 1992-10-14 1997-04-08 Endodermic Medical Technologies Company Ultrasonic transdermal system for withdrawing fluid from an organism and determining the concentration of a substance in the fluid
US5582184A (en) * 1993-10-13 1996-12-10 Integ Incorporated Interstitial fluid collection and constituent measurement
US5820570A (en) * 1993-10-13 1998-10-13 Integ Incorporated Interstitial fluid collection and constituent measurement
US5746217A (en) * 1993-10-13 1998-05-05 Integ Incorporated Interstitial fluid collection and constituent measurement
US5722397A (en) * 1993-11-15 1998-03-03 Altea Technologies, Inc. Enhancement of transdermal monitoring applications with ultrasound and chemical enhancers
US5885211A (en) * 1993-11-15 1999-03-23 Spectrix, Inc. Microporation of human skin for monitoring the concentration of an analyte
US5706607A (en) * 1994-09-17 1998-01-13 Frey; Harry Magnetic door seal
US5588808A (en) * 1994-12-08 1996-12-31 Hytech Pumps International, Inc. Pump pressure multiplier
US6122536A (en) * 1995-07-06 2000-09-19 Animas Corporation Implantable sensor and system for measurement and control of blood constituent levels
US5662616A (en) * 1995-07-07 1997-09-02 Bousquet; Gerald G. Transcutaneous access device
US6099508A (en) * 1995-07-07 2000-08-08 Bousquet; Gerald G. Transcutaneous access device
US5913833A (en) * 1997-02-07 1999-06-22 Abbott Laboratories Method and apparatus for obtaining biological fluids
US5833655A (en) * 1997-05-15 1998-11-10 L. Vad Technology, Inc. Percutaneous access device having removable turret assembly

Cited By (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10307253B2 (en) 1999-08-09 2019-06-04 Edwards Lifesciences Corporation System for improving cardiac function by sealing a partitioning membrane within a ventricle
US10307147B2 (en) 1999-08-09 2019-06-04 Edwards Lifesciences Corporation System for improving cardiac function by sealing a partitioning membrane within a ventricle
US9017394B2 (en) 1999-08-09 2015-04-28 Cardiokinetix, Inc. Retrievable cardiac devices
US8672827B2 (en) 1999-08-09 2014-03-18 Cardiokinetix, Inc. Cardiac device and methods of use thereof
US8657873B2 (en) 1999-08-09 2014-02-25 Cardiokinetix, Inc. System for improving cardiac function
US9872767B2 (en) 1999-08-09 2018-01-23 Edwards Lifesciences Corporation Retrievable cardiac devices
US8747454B2 (en) 1999-08-09 2014-06-10 Cardiokinetix, Inc. System for improving cardiac function
US9694121B2 (en) 1999-08-09 2017-07-04 Cardiokinetix, Inc. Systems and methods for improving cardiac function
US10064696B2 (en) 2000-08-09 2018-09-04 Edwards Lifesciences Corporation Devices and methods for delivering an endocardial device
US9078660B2 (en) 2000-08-09 2015-07-14 Cardiokinetix, Inc. Devices and methods for delivering an endocardial device
US8543184B2 (en) 2002-05-22 2013-09-24 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US9549693B2 (en) 2002-05-22 2017-01-24 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US8064977B2 (en) * 2002-05-22 2011-11-22 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US10052051B2 (en) 2002-05-22 2018-08-21 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US11020026B2 (en) 2002-05-22 2021-06-01 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US8827892B2 (en) 2002-08-01 2014-09-09 Cardiokinetix, Inc. Therapeutic methods and devices following myocardial infarction
US9592123B2 (en) 2002-08-01 2017-03-14 Cardiokinetix, Inc. Therapeutic methods and devices following myocardial infarction
US8219174B2 (en) 2003-10-31 2012-07-10 Abbott Diabetes Care Inc. Method of calibrating an analyte-measurement device, and associated methods, devices and systems
US8219175B2 (en) 2003-10-31 2012-07-10 Abbott Diabetes Care Inc. Method of calibrating an analyte-measurement device, and associated methods, devices and systems
US8684930B2 (en) 2003-10-31 2014-04-01 Abbott Diabetes Care Inc. Method of calibrating an analyte-measurement device, and associated methods, devices and systems
US8761857B2 (en) 2004-02-09 2014-06-24 Abbott Diabetes Care Inc. Analyte sensor, and associated system and method employing a catalytic agent
US8165651B2 (en) * 2004-02-09 2012-04-24 Abbott Diabetes Care Inc. Analyte sensor, and associated system and method employing a catalytic agent
US20050240155A1 (en) * 2004-04-27 2005-10-27 Conlon Sean P Surgically implantable injection port having a centered catheter connection tube
US8348842B1 (en) 2004-05-14 2013-01-08 Flint Hills Scientific, L.L.C. Method and system for implantable glucose monitoring and control of a glycemic state of a subject
US7988630B1 (en) 2004-05-14 2011-08-02 Flint Hills Scientific Llc Method and system for implantable glucose monitoring and control of a glycemic state of a subject
US7727147B1 (en) * 2004-05-14 2010-06-01 Flint Hills Scientific Llc Method and system for implantable glucose monitoring and control of a glycemic state of a subject
US9332993B2 (en) 2004-08-05 2016-05-10 Cardiokinetix, Inc. Devices and methods for delivering an endocardial device
US9332992B2 (en) 2004-08-05 2016-05-10 Cardiokinetix, Inc. Method for making a laminar ventricular partitioning device
US8224414B2 (en) * 2004-10-28 2012-07-17 Echo Therapeutics, Inc. System and method for analyte sampling and analysis with hydrogel
US20060094945A1 (en) * 2004-10-28 2006-05-04 Sontra Medical Corporation System and method for analyte sampling and analysis
US7985199B2 (en) * 2005-03-17 2011-07-26 Unomedical A/S Gateway system
US20110178362A1 (en) * 2006-02-06 2011-07-21 Evans Michael A Systems and methods for volume reduction
US10117614B2 (en) 2006-02-28 2018-11-06 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US8506482B2 (en) 2006-02-28 2013-08-13 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US11872039B2 (en) 2006-02-28 2024-01-16 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US10617823B2 (en) 2007-02-15 2020-04-14 Abbott Diabetes Care Inc. Device and method for automatic data acquisition and/or detection
US11264133B2 (en) 2007-06-21 2022-03-01 Abbott Diabetes Care Inc. Health management devices and methods
US11276492B2 (en) 2007-06-21 2022-03-15 Abbott Diabetes Care Inc. Health management devices and methods
US20100076284A1 (en) * 2007-06-21 2010-03-25 Abbott Diabetes Care Inc. Health Management Devices and Methods
US8617069B2 (en) 2007-06-21 2013-12-31 Abbott Diabetes Care Inc. Health monitor
US11166656B2 (en) 2009-02-03 2021-11-09 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11006871B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11006870B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11006872B2 (en) 2009-02-03 2021-05-18 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11213229B2 (en) 2009-02-03 2022-01-04 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11202591B2 (en) 2009-02-03 2021-12-21 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US11872370B2 (en) 2009-05-29 2024-01-16 Abbott Diabetes Care Inc. Medical device antenna systems having external antenna configurations
US11793936B2 (en) 2009-05-29 2023-10-24 Abbott Diabetes Care Inc. Medical device antenna systems having external antenna configurations
US10492685B2 (en) 2009-08-31 2019-12-03 Abbott Diabetes Care Inc. Medical devices and methods
US10136816B2 (en) 2009-08-31 2018-11-27 Abbott Diabetes Care Inc. Medical devices and methods
USD1010133S1 (en) 2009-08-31 2024-01-02 Abbott Diabetes Care Inc. Analyte sensor assembly
US20110098525A1 (en) * 2009-10-26 2011-04-28 Kermode James R Ventricular volume reduction
US8790242B2 (en) 2009-10-26 2014-07-29 Cardiokinetix, Inc. Ventricular volume reduction
US9039597B2 (en) 2009-10-26 2015-05-26 Cardiokinetix, Inc. Ventricular volume reduction
US10028835B2 (en) 2009-10-26 2018-07-24 Edwards Lifesciences Corporation Ventricular volume reduction
US9364327B2 (en) 2009-10-26 2016-06-14 Cardiokinetix, Inc. Ventricular volume reduction
US9532737B2 (en) 2011-02-28 2017-01-03 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US9465420B2 (en) 2011-10-31 2016-10-11 Abbott Diabetes Care Inc. Electronic devices having integrated reset systems and methods thereof
US9069536B2 (en) 2011-10-31 2015-06-30 Abbott Diabetes Care Inc. Electronic devices having integrated reset systems and methods thereof
WO2015052235A1 (en) * 2013-10-11 2015-04-16 Qstar Medical Sas Vascular access port devices with incorporated sensors
EP2859911A1 (en) * 2013-10-11 2015-04-15 qSTAR Medical SAS Vascular access port devices with incorporated sensors
US11229382B2 (en) 2013-12-31 2022-01-25 Abbott Diabetes Care Inc. Self-powered analyte sensor and devices using the same
US11690720B2 (en) 2014-09-28 2023-07-04 Edwards Lifesciences Corporation Systems and methods for treating cardiac dysfunction
US10751183B2 (en) 2014-09-28 2020-08-25 Edwards Lifesciences Corporation Apparatuses for treating cardiac dysfunction
EP3243549A1 (en) * 2016-05-12 2017-11-15 Renishaw plc Percutaneous access apparatus
WO2017194933A1 (en) * 2016-05-12 2017-11-16 Renishaw Plc Percutaneous access apparatus
US11638811B2 (en) 2016-05-12 2023-05-02 Renishaw Plc Percutaneous access apparatus
CN109414576A (en) * 2016-05-12 2019-03-01 瑞尼斯豪公司 Transcutaneous access device
US10898330B2 (en) 2017-03-28 2021-01-26 Edwards Lifesciences Corporation Positioning, deploying, and retrieving implantable devices
US20190308004A1 (en) * 2018-04-04 2019-10-10 Marius Saines Low profile self-sealing access port
WO2019195353A1 (en) * 2018-04-04 2019-10-10 Sainess Marius Low profile self-sealing access port

Also Published As

Publication number Publication date
US6459917B1 (en) 2002-10-01

Similar Documents

Publication Publication Date Title
US6459917B1 (en) Apparatus for access to interstitial fluid, blood, or blood plasma components
US7166074B2 (en) Reusable analyte sensor site and method of using the same
US4777953A (en) Capillary filtration and collection method for long-term monitoring of blood constituents
US5002054A (en) Interstitial filtration and collection device and method for long-term monitoring of physiological constituents of the body
US4854322A (en) Capillary filtration and collection device for long-term monitoring of blood constituents
CA2424288C (en) Device and method for obtaining interstitial fluid from a patient for diagnostic tests
CA2787010C (en) Combined sensor and infusion sets
US6368274B1 (en) Reusable analyte sensor site and method of using the same
US6254586B1 (en) Method and kit for supplying a fluid to a subcutaneous placement site
DK2732837T3 (en) Combined sensor and infusion set for use on separate sites
US5951521A (en) Subcutaneous implantable sensor set having the capability to remove deliver fluids to an insertion site
US20090312622A1 (en) Device And Method For Determining A Value Of A Physiological Parameter Of A Body Fluid
US20060253085A1 (en) Dual insertion set
WO2000035530A1 (en) Insertion sets with micro-piercing members for use with medical devices and methods of using the same
MXPA02005068A (en) Tissue interface device.
WO2007054317A1 (en) Determining a value of a physiological parameter
US20080234563A1 (en) Device for and Method of Delivery and Removal of Substances in and From a Tissue or Vessel

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION