CN102406979A - Method and system for leading macromolecule substances into living target cells - Google Patents
Method and system for leading macromolecule substances into living target cells Download PDFInfo
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- CN102406979A CN102406979A CN2010105366124A CN201010536612A CN102406979A CN 102406979 A CN102406979 A CN 102406979A CN 2010105366124 A CN2010105366124 A CN 2010105366124A CN 201010536612 A CN201010536612 A CN 201010536612A CN 102406979 A CN102406979 A CN 102406979A
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Abstract
A method and a system for leading macromolecule substances into target cells includes an image picking unit, an image merging unit, an injection unit, and an energy conversion module. The ultrasound energy conversion module comprises ultrasound transducers or tweeters. The image picking unit is used for picking up the three-dimensional (3D) and the 3D blood vessel photographic images of the tissue or organ where the target cells locate. The image merging unit is used for merging the 3D structure images into the 3D blood vessel photographic images, therefore choosing a blood vessel passage fully covering the target cells for transmitting the macromolecule substances. The injection unit is used for injecting liquid and transmitting the macromolecule substances to the target cells. The energy conversion module is used for exerting energy to activate the liquid to perform biological effects. The energy conversion module comprises ultrasound transducers or tweeters, thereby forming non-permanent holes in the cell membranes of the target cells. The macromolecule substances enter into the target cells through the non-permanent holes.
Description
The cross reference of related application
The application is with filing an application on August 19th, 2008 and denomination of invention is the U.S. Patent application the 12/194th of " macromolecular substances being imported the method and system of live body target cell " (METHOD AND SYSTEM FOR LEADING MACROMOLECULE SUBSTANCE INTO LIVING TARGET CELLS); Filed an application on May 15th, No. 497 1 and denomination of invention is the U.S. Patent application the 12/121st of " macromolecular substances being imported the method and system of live body target cell "; Got permission on August 19th, No. 712 1 patent for the time being denomination of invention be the United States Patent (USP) the 7th of " macromolecular substances being imported the method and system of live body target cell "; Above-mentioned whole patent application documents such as No. the 092128522nd, 415, No. 302 and the Taiwan patent application of filing an application on October 15th, 2003 and patent are incorporated this paper by reference into.
Technical field
The present invention relates generally to macromolecular substances is imported the method and system of target cell, more particularly, relate to the penetrance that the using ultrasound ripple is regulated the cell membrane of target cell, effectively the macromolecular substances of low dosage is imported the method and system of target cell thus.
Background technology
The histiocyte of human body is stimulated by inside or outside injurious factor sometimes and causes and catch an illness.As a result, the number of the cell of catching an illness increases sharply, and the cell transfer of catching an illness is to health tissues, thereby forms tumor.Tumor comprises benign tumor and malignant tumor.Compare with benign tumor, malignant tumor is difficult to cure, and bigger to human harm.
At present, have every year 5,000,000 people to die from tumor, and malignant tumor is main killer.Along with the development of medical science, multiple advanced person's diagnosing tumor method and Therapeutic Method is provided.Tumor therapeuticing method mainly comprises surgical operation, chemotherapy and X-ray therapy.In chemotherapeutic treatment, scatter the toxicity that medicine produced owing to hang down the medication accuracy to human body, limitation that this remains unsolved and defective are often being engulfed the health of tumor patient.Therefore, realize maximum hospital benefit like minimum drug dose how, and how to promote the medication accuracy, the problem of demanding urgently overcoming for people.
Recent discovers that (shock wave lithotripsy SWL) can produce microvesicle at cell peripheral to extracorporeal shock wave.These microvesicles form the impermanency hole in cell membrane.Therefore, promote the penetrance of cell membrane and realize the better medicament absorbability.United States Patent (USP) the 6th, 298, No. 264 a kind of methods that promote the cell membrane penetrance of exposure.This method use first impulse wave (pulsed wave, PW) and second impulse wave produce the microvesicle of encircling cell.These microvesicles form the impermanency hole in cell membrane, to promote the penetrance of cell membrane.This method can increase to 90% with the penetrance of cell membrane.Therefore, only need low drug dose.Yet how accurately this method does not disclose locatees this target cell and how to promote the medication degree of accuracy.Therefore, still need accurately locate target cell and promote the method for medication degree of accuracy.
Summary of the invention
Main purpose of the present invention is, the method and system that macromolecular substances imported effectively the target cell are provided.
Another object of the present invention is to, the method and system that are applied in the gene conveying are provided, increase the efficient that gene is carried.
A purpose more of the present invention is, the method and system that are applied in the gene conveying are provided, and promotes the efficient of gene therapy.
Another purpose of the present invention is, the method and system that promote the medication degree of accuracy are provided.
Another purpose more of the present invention is, the method and system that reduce drug dose and effectively medicine is imported tumor cell are provided.
According to above-mentioned and other purpose, the present invention provides the method and system that macromolecular substances imported live body target cell.This comprises the system that macromolecular substances imports live body target cell: image acquisition unit, this image acquisition unit are used to capture three-dimensional (3D) the structure image of residing tissue of target cell or organ and the 3D vasography image of residing tissue of target cell or organ; Image synthesis unit, this image synthesis unit select to contain fully the blood vessel access of the target cell that transmits macromolecular substances thus in order to 3D structure image is integrated with 3D vasography image; Injecting unit, this injecting unit are used for injecting fluid and transmit macromolecular substances to this target cell; Energy conversion module, this energy conversion module is used to apply energy, with this liquid of activation and produce biological effect; Wherein, this energy conversion module comprises the ultrasound wave modular converter that comprises ultrasonic transducer or high frequency microphone (tweeter), in the cell membrane of this target cell, forms the impermanency hole thus; Wherein, macromolecular substances gets in the target cell through the impermanency hole in the target cell film.
This comprises the method that macromolecular substances imports live body target cell: at first, and the acquisition residing tissue of target cell or the 3D structure image of organ and the 3D vasography image of residing tissue of target cell or organ; The second, 3D structure image is integrated with 3D vasography image, select to contain fully the blood vessel access of the target cell that transmits macromolecular substances; The 3rd, use conduit along selected blood vessel access injection microvesicle liquid (ultrasound wave or artificial blood), this microvesicle is arranged around the target cell; The 4th, apply energy with this microvesicle liquid of activation, to produce biological effect, in the cell membrane of this target cell, form the impermanency hole thus; And last, via the impermanency hole in the cell membrane,, the macromolecular substances injection is got in the target cell along selected blood vessel access.
Compare the method and system acquisition residing tissue of target cell or the 3D structure image of organ and the 3D vasography image of residing tissue of target cell or organ that macromolecular substances is imported live body target cell of the present invention with the traditional medical method and system; 3D structure image is integrated with 3D vasography image, accurately locate this target cell thus, to select to contain fully the most effectively blood vessel access of target cell; And macromolecular substances injection is got in the target cell along selected blood vessel access.Subsequently, these method and system apply the microvesicle that energy is arranged around the target cell with activation, to produce biological effect, in the cell membrane of target cell, form the impermanency hole thus.Macromolecular substances gets in the target cell through the impermanency hole in the target cell film.Therefore, the method and system that macromolecular substances is imported live body target cell of the present invention have lot of advantages, like low drug dose, low cost, accurately medication and effective curative effect.
For further understanding of the present invention being provided, following detail specifications illustrative specific embodiment of the present invention and embodiment; Will be appreciated that this detail specifications only provides illustrative of the present invention, but not as limitation of the scope of the invention.
Description of drawings
Figure 1A is the block schematic diagram that basic structure illustrated of the system that macromolecular substances is imported live body target cell according to an advantageous embodiment of the invention.
Figure 1B to Fig. 1 D is respectively perspective view, front view and the side view of the ultrasonic wave module that is used for power conversion.
Fig. 1 E has illustrated disk perimeter, and several diameters are arranged is 2 centimetres of (cm) low-yield ultrasonic transducers or high frequency microphone; Its frequency range is that 20 kilo hertzs (KHz) are to 50KHz; The position is apart from this disk 20cm place, and each low-yield ultrasonic transducer or the micropkonic intensity of acoustic wave of high frequency are 0.0375 watt (W)/square centimeter (cm
2), be 8 * 0.0375W/cm merging the zone
2=0.3W/cm
2
Fig. 1 F points out to be within the merging zone at the symmetrically arranged low-yield ultrasonic transducer of disk perimeter; Wherein, The low ultrasonic energy propagation unit of imaging guiding robotic arm control (being used for the ultrasound wave molecule carries), this disk center is a B mode ultrasound diagnostic transducer, to confirm target placement.
Fig. 1 G for before the injection nano-emulsion and after tumor, it is synthetic that wherein the left side has illustrated the 3D image of tumor entity and blood vessel thereof; The right side has illustrated injection artificial blood perfluorocarbon nano-emulsion (small white point) and has got in the tumor vessel, to fill the tumor cell clearance space.
Fig. 1 H has shown the design of ultrasonic head, and wherein left figure shows the design of ultrasound machine arm; The focal zone (merging the zone) of transducer is positioned at from the about 20cm of cephalic disc at a distance around the right figure explanation.
Fig. 1 I shows that via the computer generated image guiding, through assisting of robotic arm, low-yield hyperacoustic focal zone is accurately positioned in the real intravital predetermined treatment of tumor zone.
Fig. 1 J is the sketch map of the tumor after reaching before the treatment.
Fig. 1 K shows, the ultrasound machine arm can be independent individual or its and can be connected to or attach dress or be mounted on the imaging device.
Fig. 2 imports macromolecular substances for the system that uses Fig. 1 the flow chart that step illustrated of live body target cell.
[primary clustering symbol description]
1 imports the system of live body target cell with macromolecular substances
100 image acquisition units
110 image synthesis units
120 injecting units
130 energy conversion module
131 base part
132 imaging guiding robotic arms
134 ultrasonic propagation unit
136 disks
140 microprocessing units
150 low-yield ultrasonic transducers or high frequency microphone
A acoustic horn effect transducer or high frequency microphone
B becomes image converter.
The specific embodiment
The present invention relates generally to the method and system of macromolecular substances being introduced the target cell; Be more especially,, effectively the macromolecular substances of low dosage imported the method and system of target cell thus about the penetrance that the using ultrasound ripple is regulated the cell membrane of target cell.Appearing of following narration makes those skilled in the art can accomplish and use the present invention, and is provided in the article of patent application and important document thereof.Preferred specific embodiment that those skilled in the art are easy to this paper is disclosed and common principle and characteristic are made various modifications.Therefore, the present invention desires to be restricted to the said specific embodiment that is shown, but consistent with the maximum category of said principle disclosed herein and characteristic.
The method and system that macromolecular substances is imported live body target cell of the present invention can be applicable to multiple different field, like gene conveying, gene therapy, medicine transmission, part medication and oncotherapy.The present invention is particularly useful for oncotherapy, is more especially the treatment of solid tumor.For example, in the treatment of solid tumor, generally with computed tomography (CT) or nuclear magnetic resonance (MRI) as preliminary step.Capture the basis of three-dimensional (3D) the structure image of residing tissue of tumor cell or organ through this preliminary step as successive treatment (like surgical operation, chemotherapy and X-ray therapy).
See also Figure 1A; The basic structure illustrative in Figure 1A that accordings to the system that macromolecular substances is imported live body target cell of preferred specific embodiment of the present invention; Comprise Fig. 2, it is only made simple and clear illustrative to the primary clustering of the system 1 that macromolecular substances imported live body target cell and uses.The actual system 1 that uses can be more complicated.
The system 1 that macromolecular substances is imported live body target cell comprises image acquisition unit 100, image synthesis unit 110, injecting unit 120 and energy conversion module 130.In this specific embodiment, image acquisition unit 100, image synthesis unit 110, injecting unit 120 and energy conversion module 130 receive 140 controls of microprocessing unit.
Image acquisition unit 100 is used to capture the 3D structure image of residing tissue of target cell or organ and the 3D photographic image of the residing blood vessel of acquisition target cell.In this specific embodiment, image acquisition unit 100 is one of following: CT device, MRI device and vasography device.The target cell is at least a tumor cell.
Usually, the CT device utilizes the tomography of fan-shaped X ray from the axial scan human body, and utilizes the string detector to receive the signal that penetrates human body.When the X ray emitter was fixed on ad-hoc location, said detector can receive signal from the certain layer of correspondence.When the X ray transmitter loop when a tomography rotates, be positioned the reverse detector of X ray emitter and can receive from one deck but the signal of different directions.The said signal of computer analysis also calculates the Density Distribution of forming this layer composition point, shows the image of the dot pattern with different GTGs (gray level) subsequently, is used for strengthening the resolution of this layer.With regard to the scanning brain, the aspect of about 15 1 cm thicks promptly can contain whole brain and XIAONAO fully, and can show the fine structure of brain.Therefore, can detect whether water brain or clot are arranged in the brain.At present, whole body type scanner can be in 30 seconds interscan livers under the patient holds the breath the interferential situation that moves with very big reduction breathing and intestinal fast.Also can use scanner fast detecting and other disease of clear demonstration such as small liver cancer, adrenal gland neoplasms or pancreatic diseases.
The MRI device is used to provide multilamellar photo clearly.The MRI device utilizes electromagnetic wave to stimulate the patient, and utilizes detector to be received from the echo that the patient discharges.After repeatedly complicated stimulation-echo process, can realize high resolution image according to huge echo data.Discharge different echoes after the different tissues irriate, thereby in the image of gained, produce distinct comparison.From the CT device of axial (more than adding a coronal plane the brain) scanning tomography, the MRI device can scan the part of human body from different angles than usually, and like the specific part of similar hypophysis cerebri or brain stem, its structure can clearly show.Among another embodiment, the MRI device does not utilize X ray, can in 15 minutes, accomplish scanography, therefore, significantly reduces the radiation to human body.Moreover; A lot of diseases in the nervous system, like the little tumor of the slight apoplexy of brain stem, contiguous skull bottom or bone marrow disease (like the acute injury or the intervertebral disk hernia (lumbar disc herniation, LDH)) of bone marrow; Be generally the CT device and ignore, but can detect easily through the MRI device.In skeleton and musculature, the MRI device is particularly useful for the disease that inspection influences joint and essence (parenchyma), like sport injury.The MRI device also can be in order to the inspection bile duct.Use in the BDE of MRI device; Can be at the image that in 20 seconds, obtains this bile duct under the situation of holding the breath; Thereby can avoid the retrograde pancreatic duct photography of endoscope (endoscopic retrograde cholangiopancreatography, misery ERCP).
Although the MRI device has above-mentioned lot of advantages, its cost that is used to check is too high, makes the MRI inspection to be widely used.Moreover, if patient wear pace maker or other physiological monitor, with the checking efficiency of restriction use MRI device.Therefore, the proper method of the 3D structure image of acquisition tissue or organ should be according to the tumor present position, and patient personal considerations and selecting.Although CT device and MRI device can capture the 3D structure image of tissue or organ effectively; But use in the medication of injecting method; The transfer passage of general uncontrollable medicine; And be not sure of and use the medicine of tube injection whether to transfer to whole tumor cells effectively, therefore, the curative effect extreme difference.In order to overcome these problems, further comprise the vasography device according to the image acquisition unit 100 that macromolecular substances is imported the system 1 of live body target cell of the present invention.
This vasography device is gone into specific dye injection in the blood vessel, to generate a series of blood vessel images.For example, in the inspection of cardiovascular system, from groin femur is bored a hole earlier, put into conduit subsequently, reverse transfer gets in the particular blood vessel again.Subsequently, developing agent is injected fast, carry out the consecutive image acquisition simultaneously through conduit.Therefore, can obtain the organ of blood vessel inflow such as the blood flow situation of brain, heart, liver or kidney.Moreover; Can use 3D to rebuild vasography; As (General Electric, the diagnostic of GE) making and intervention property Angiography system (Advantx LCA+), cardiovascular and Angiography imaging system (Advantx LCV+) and biplane neural blood vessel photography system (Advantx LCN+) capture the 3D vasography image of residing tissue of tumor cell or organ to use General Electric Co. Limited.
Image synthesis unit 110 will be integrated with in the 3D vasography image through the 3D structure image of image acquisition unit 100 acquisition, with positioning tumor cell accurately, and the suitable blood vessel access of selecting to contain fully tumor cell.As stated; After CT device and 3D vasography device and/or MRI device or 3D vasography device captured the 3D structure image and 3D vasography image of tumor cell respectively, image synthesis unit 110 was carried out image synthetic operations (also being called tissue charts).Image after synthetic is used for accurately positioning tumor cell, and is used for selecting the most effectively blood vessel access.Via conduit, along selected blood vessel access injectable drug, guarantee thus medicine is transferred to tumor cell effectively, and realize thoroughly treatment and low recurrence chance.
In addition, after image is synthetic, show that accurately tumor reaches the relative position around the blood vessel of tumor.Except accurately the positioning tumor cell, can also select the most effectively blood vessel access.Therefore, can medicine be transferred to whole tumor cells along the most effective blood vessel access through conduit.
Injecting unit 120 utilizes conduit that microvesicle liquid and macromolecular substances are injected in the target cell.Macromolecular substances gets in the target cell through the impermanency hole that microvesicle forms in the cell membrane of target cell.In this specific embodiment, via the conduit of injecting unit 120, along selected blood vessel access, injection microvesicle liquid also distributes around tumor cell.Through blood vessel, bubble is preferably dimensioned to be less than 10 microns for smooth-goingly.Via the step of tube injection medicine can be before in cell membrane, forming the impermanency hole or after carry out.Because medicine gets into tumor cell through the hole that in cell membrane, forms, the dosage of medicine can be reduced to 1% of general dose, and realizes more effectively curative effect, the infringement of avoiding drug toxicity that other cells are caused, and save great amount of cost.
Figure 1B to Fig. 1 D is respectively perspective view, front view and the side view of the ultrasonic energy modular converter 130 of power conversion.Ultrasonic energy modular converter 130 comprises base part 131 and imaging guiding robotic arm 132.Module 130 comprises ultrasonic propagation unit 134, and it comprises and has transducer and the micropkonic disk that is used for the radiation ultrasonic energy of high frequency.The low ultrasonic energy propagation unit 134 of imaging guiding robotic arm 132 controls (molecule that is used for ultrasonic activation is carried).In one specific embodiment, the center of disk 136 is ultrasound wave (B pattern) diagnosis transducer (not shown), with the check target placement.
Fig. 1 E indicates disk perimeter and has several low-yield ultrasonic transducers or high frequency microphone 150 (frequency range be 20 to 50KHz), and energy to merge regional adjustable strength range be about 0.2 to 0.3 watt (W)/square centimeter (cm
2) (apart from the about 20cm of disk).
Fig. 1 F is indicated in the symmetrically arranged low-yield ultrasonic transducer of disk perimeter or high frequency microphone (frequency range be 20 to 50KHz), is in as in disk 20cm merging zone far away, and the ultrasonic intensity about 0.2 that merges the zone is to 0.3W/cm
2Scope in.Through using energy conversion module 130, effective conveying of energy can be provided to tumor etc.
Fig. 1 G for before the injection nano-emulsion and after tumor, it is synthetic that wherein the left side has illustrated the 3D image of tumor entity and blood vessel thereof; The right side illustrates artificial blood perfluorocarbon nano-emulsion (small white point) is injected in the tumor vessel, to fill the tumor cell gap.
The left figure of Fig. 1 H shows the design of ultrasound machine arm.The cephalic disc of ultrasound machine arm has 8 symmetrically arranged low-yield transducers or high frequency microphone (frequency range be 20 to 50KHz); The micropkonic size of these transducers or high frequency is about the diameter of 2cm.The micropkonic focal zone of these transducers or high frequency is about 20cm place from the surface of this dish.The diameter of cephalic disc is about 15 to 20cm.There is one to be arranged at wherein B pattern diagnostic transducer (frequency 3 to 8 megahertzes (MHz), diameter are 3 to 5cm, and maximum penetration is 20 to 30cm) in the dish.
The focal zone (merging the zone) of transducer is positioned the about 20cm place apart from cephalic disc around the right figure explanation of Fig. 1 H.The ultrasonic energy level that it should be noted that focal zone be every square centimeter about 0.2 to 0.3W, it is for low-frequency ultrasonic waves cavitation (acoustic horn effect) best results, but in FDA ultrasound wave security guide, is good.These 8 independently the path of ultrasound beamformer have low-down ultrasonic energy, it can not create acoustic horn effect, also can't obtain any non-physiological effect of desiring.In other words, only focal zone can have the therapeutic acoustic horn effect, and cumulative energy is safe for the patient in this focal zone.
Fig. 1 I has shown the accurately energy-activated of target area, and wherein, via the computer generated image guiding, through assisting of robotic arm, low-yield hyperacoustic focal zone is accurately positioned in the real intravital predetermined treatment of tumor zone.
Fig. 1 J is the sketch map of the tumor after reaching before the treatment.The entity of tumor significantly shrinks after treatment.
Fig. 1 K has shown CT scanner with ultrasound wave arm (in imaging of same site and treatment), and the ultrasound machine arm can be independent individual or its and can be connected to or attach and be loaded on or be mounted on the imaging device (like CT, MR, PET scanner).
See also Fig. 2, this figure has illustrated and has used said system 1 macromolecular substances to be imported the step of live body target cell.
In step S201, the 3D structure image of image acquisition unit 100 acquisition residing tissues of tumor cell or organ, and the 3D vasography image of residing tissue of tumor cell or organ.Carry out step S202 subsequently.
In step S202, image synthesis unit 110 is integrated with 3D vasography image with 3D structure image, with positioning tumor cell accurately and select to contain fully the blood vessel access of the target cell that is used to transmit this macromolecular substances.Carry out step S203 subsequently.
In step S203, injecting unit 120 is via selected blood vessel access, and injection microvesicle liquid is with around tumor cell.Carry out step S204 subsequently.
In step S204, energy conversion module 130 is used transducer or high frequency microphone, applies the ultrasound wave that is used for activation microvesicle liquid, to produce biological effect, in the cell membrane of tumor cell, forms the impermanency hole thus.Carry out step S205 subsequently.
In step S205, injecting unit 120 is injected into macromolecular substances in the tumor cell via the impermanency hole in the cell membrane of tumor cell.
In another instantiation of the present invention, with artificial blood as the microvesicle liquid infusion and around tumor cell.Artificial blood is meant that it satisfies some function of blood biology, especially in human body.Because human blood is also carried out other function, so it is more accurate to be called oxygen therapy except carrying out the oxygen carrier function.For example, leukocyte defence infectious disease, and platelet is participated in blood clotting.An instance of artificial blood is perfluorocarbon (PFC) nano-emulsion.Therefore this artificial blood has the very little volume of about 150 nanometers, can not stop up blood capillary, and the crack of this artificial blood between can intravasation.Therefore, can improve when using conduit because the anoxia that low blood flow causes.
This 3D vasography image of ultrasound wave developing agent acquisition also capable of using.This ultrasound wave developing agent is made up of the microvesicle that is wrapped in the specific containment vessel.First generation developing agent is processed by the bubble of its internal package air, the albunex (mallinckrodt) that for example has the average external volume of 4 microns (μ m) and processed by the albumin of ultrasonic vibration.Other ultrasound wave developing agent comprises echovist, echogen, levovist, aerosomes etc.A new generation's ultrasound wave developing agent is to be processed by the gas that is insoluble in water such as fluorine carbon or sulfur tetrafluoride.Phospholipid, albumin, polymer, surfactant and other material are added in this gas.A new generation's ultrasound wave developing agent can prolong its life-span in blood, and strengthens the ultrasonic propagation effect.The gravel size decision of this ultrasound wave developing agent is no more than 10 microns, so this ultrasound wave developing agent can pass through this blood capillary smoothly.Can or use the ultrasound wave developing agent that uses in the tube injection method and system of the present invention through intravenous injection.
When applying the ultrasound wave of 1 MPa (Mpa) intensity, the bubble of developing agent can produce Non-Linear Vibration, and the emission harmonic ringing.Because the harmonic ringing of bubble is more a lot of by force than the harmonic ringing of tissue, the signal of developing agent is completely different in the signal of tissue, therefore can clearly show the vascularity of organizing situation and tumor of the blood circumstance that comprises cardiac muscle and kidney.As stated, 3D structure image is integrated with after the 3D vasography image, selected the most effectively blood vessel access.Via selected passage, the medicine of injection oncotherapy is with around tumor cell.
With the medicine injection is around after the tumor cell; Apply the ultrasound wave of use transducer or the micropkonic 1Mpa at least of high frequency intensity or the Sasser of suitable intensity; With activation microvesicle or ultrasound wave developing agent and carry out intensive bubble and move, in cell membrane, form the impermanency hole thus, increase the penetrance of cell membrane thus; Reduce dosage immediately significantly, and keep effective curative effect.Perhaps, can in the cell membrane of tumor cell, form impermanency hole injectable drug before, realize accurate medication effect same as described above thus.
In addition, the system 1 that macromolecular substances is imported live body target cell of the present invention further comprises the date processing electronic installation or operates with the date processing electronic installation, is used for handling the data that produce in system's 1 progress of work.The date processing electronic installation can be personal computer (PC), mobile computer (NB), server, work station, PDA(Personal Digital Assistant), liquid crystal display (LCD) computer or flat computer etc.The date processing electronic installation comprises display unit and input block.Display unit is used to show the synthetic processing of the image of carrying out through image synthesis unit 110, through the medicament injection process of injecting unit 120 execution, and passes through the power transfer situation that energy conversion module 130 is carried out.Input block is used to import and of the present invention macromolecular substances is imported the instruction and/or the parameter of the system 1 of live body target cell, to this date processing electronic installation.
Obviously, to those skilled in the art, above-mentioned description appearance is the illustrative of certain specific embodiments of the present invention and embodiment.Therefore the present invention should contain various modifications and the change that the structure of the present invention and the operation of this paper announcement are done, and it falls in the defined protection category of claims of the present invention.
Although disclose the present invention according to the specific embodiment that is shown already, those skilled in the art will be easy to cognition, but said specific embodiment is changed, and this change will be in spirit of the present invention and the category.Thus, those skilled in the art can make a lot of modifications to the present invention, and do not deviate from the spirit and the category of claims of the present invention.
Claims (15)
1. one kind imports the system of live body target cell with macromolecular substances, it is characterized in that, comprises:
Image acquisition unit, this image acquisition unit are used to capture the 3D structure image of residing tissue of this target cell or organ and the 3D vasography image of residing tissue of this target cell or organ;
Image synthesis unit, this image synthesis unit are used for this 3D structure image is incorporated into this 3D vasography image, select to contain fully the blood vessel access of the target cell that transmits this macromolecular substances thus;
Injecting unit, this injecting unit are used for injecting fluid and transmit this macromolecular substances to this target cell;
Energy conversion module, this energy conversion module is used to apply energy, with this liquid of activation and produce biological effect, in the cell membrane of this target cell, forms the impermanency hole thus; Wherein, this energy conversion module comprises and comprises ultrasonic transducer or the micropkonic ultrasound wave modular converter of high frequency, and this macromolecular substances gets in this target cell through the impermanency hole in the cell membrane of this target cell.
2. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that this ultrasound wave modular converter comprises base part, image guide robotic arm and ultrasonic propagation unit.
3. according to claim 2 macromolecular substances is imported the system of live body target cell, it is characterized in that this ultrasonic propagation unit comprises this ultrasonic transducer or high frequency microphone.
4. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that, this image acquisition unit is one of following: computer tomography device, MR imaging apparatus and vasography device.
5. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that this 3D vasography image obtains through using 3D to rebuild vasography.
6. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that, this liquid is one of following: microvesicle liquid, artificial blood and ultrasound wave developer solution.
7. according to claim 6 macromolecular substances is imported the system of live body target cell, it is characterized in that the volume of this liquid is less than 10 microns.
8. according to claim 7 macromolecular substances is imported the system of live body target cell, it is characterized in that, this comprises the ultrasound wave that ultrasonic transducer or the micropkonic ultrasound wave modular converter of high frequency send 20KHz to 50KHz.
9. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that, be used for one of following: gene conveying, gene therapy, medicine transmission, part medication and treatment of solid tumors.
10. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that this further comprises the date processing electronic installation with the system that macromolecular substances imports live body target cell.
11. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that this operates the system that macromolecular substances imports live body target cell with the date processing electronic installation.
12. according to claim 10 macromolecular substances is imported the system of live body target cell, it is characterized in that this date processing electronic installation comprises:
Display unit, this display unit are used to show the image building-up process that this image synthesis unit carries out, the medicament injection process that this injecting unit is carried out, and, comprise the power transfer situation of ultrasonic transducer or micropkonic this energy conversion module of high frequency; And
Input block, this input block are used for inputing to this date processing electronic installation to the instruction and/or the parameter that macromolecular substances are imported the system of live body target cell.
13. the system that macromolecular substances is imported live body target cell according to claim 10; It is characterized in that this date processing electronic installation is one of following: personal computer, mobile computer, server, work station, personal digital assistant, liquid crystal display computer and flat computer.
14. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that this ultrasound wave modular converter is arranged to independent individual.
15. according to claim 1 macromolecular substances is imported the system of live body target cell, it is characterized in that this comprises that ultrasonic transducer or the micropkonic ultrasound wave modular converter of high frequency are positioned at this image synthesis unit.
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| US12/888,245 US20110071381A1 (en) | 2003-10-15 | 2010-09-22 | Method and system for leading macromolecule substances into living target cells |
| US12/888,245 | 2010-09-22 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020098601A1 (en) * | 2018-11-12 | 2020-05-22 | 深圳大学 | Percutaneous vaccine delivery device employing acoustically induced micropore array |
| CN111905248A (en) * | 2020-08-14 | 2020-11-10 | 沈阳北部医院 | Facial nerve targeted decompression treatment method and device and computer equipment |
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| US20030078227A1 (en) * | 1998-07-02 | 2003-04-24 | Greenleaf James F. | Site-directed transfection with ultrasound and cavitation nuclei |
| US20050038340A1 (en) * | 1998-09-18 | 2005-02-17 | University Of Washington | Use of contrast agents to increase the effectiveness of high intensity focused ultrasound therapy |
| US20040030227A1 (en) * | 2002-05-16 | 2004-02-12 | Barbara Ann Karmanos Cancer Institute | Method and apparatus for combined diagnostic and therapeutic ultrasound system incorporating noninvasive thermometry, ablation control and automation |
| CN1683542A (en) * | 2004-04-16 | 2005-10-19 | 田德扬 | Method and its system for leading large molecular matter into target cell |
| CN101028524A (en) * | 2006-03-03 | 2007-09-05 | 重庆融海超声医学工程研究中心有限公司 | Supersonic microvesicle target positioning controlled-release/gene device and target transferring method |
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| WO2020098601A1 (en) * | 2018-11-12 | 2020-05-22 | 深圳大学 | Percutaneous vaccine delivery device employing acoustically induced micropore array |
| CN111905248A (en) * | 2020-08-14 | 2020-11-10 | 沈阳北部医院 | Facial nerve targeted decompression treatment method and device and computer equipment |
| CN111905248B (en) * | 2020-08-14 | 2022-03-22 | 沈阳北部医院 | Facial nerve targeted decompression treatment method and device and computer equipment |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201212892A (en) | 2012-04-01 |
| TWI432182B (en) | 2014-04-01 |
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