초록 ▼

A system, method, and device for non-invasive body fluid sampling is provided. According to one embodiment of the present invention, the system includes a controller that controls the generation of ultrasound; an ultrasonic applicator that applies the ultrasound to an area of biological membrane; a

A system, method, and device for non-invasive body fluid sampling is provided. According to one embodiment of the present invention, the system includes a controller that controls the generation of ultrasound; an ultrasonic applicator that applies the ultrasound to an area of biological membrane; a receiver that contacts the area of biological membrane and receives body fluid through and out of the area of biological membrane; and a meter that interacts with the receiver and detects the presence of at least one analyte in the body fluid in the receiver. The receiver may include a membrane and a medium, such as a hydrogel, a fluid, or a liquid, that is contained in the membrane. According to one embodiment of the present invention, the method includes the steps of (1) identifying an area of biological membrane having a permeability level; (2) increasing the permeability level of the area of biological membrane; (3) contacting the area of biological membrane with a receiver; (4) extracting body fluid through and out of the area of biological membrane; (5) providing an external force to enhance the body fluid extraction; (6) collecting the body fluid in the receiver; (7) analyzing the collected body fluid for the presence of at least one analyte; and (8) providing the results of the step of analyzing the body fluid.

대표청구항 ▼

What is claimed is: 1. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane by applying ultrasound having a frequency range of from about

What is claimed is: 1. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane by applying ultrasound having a frequency range of from about 10 kHz to about 500 kHz to the area of biological membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of the area of biological membrane and into the receiver; providing an external force to enhance the extraction of the at least one analyte; continuously analyzing the at least one analyte; and providing the results of the step of continuously analyzing the at least one analyte. 2. The method of claim 1, wherein the step of increasing the permeability level of the area of biological membrane comprises: applying ultrasound having a frequency range of from about 20 kHz to about 150 kHz to the area of biological membrane. 3. The method of claim 1, wherein the step of increasing the permeability level of the area of biological membrane comprises: applying ultrasound having a frequency of about 50 kHz to the area of biological membrane. 4. The method of claim 1, wherein the step of increasing the permeability level of the area of biological membrane comprises: increasing the permeability level of the area of biological membrane to a predetermined level. 5. The method of claim 1, wherein the step of increasing the permeability level of the area of biological membrane comprises: increasing the permeability level of the biological membrane with a method selected from the group consisting of: creating physical micropores in the area of biological membrane; physically disrupting lipid bilayers in the area of biological membrane; chemically modifying lipid bilayers in the area of biological membrane; physically disrupting the stratum corneum in the area of biological membrane; and chemically modifying the stratum corneum in the area of biological membrane. 6. The method of claim 1, wherein the step of providing an external force to enhance the extraction of the at least one analyte comprises: generating at least one osmotic force to enhance the extraction of the at least one analyte. 7. The method of claim 6, wherein the step of generating at least one osmotic force to enhance the extraction of the at least one analyte comprises: generating the at least one osmotic force by applying at least one osmotic agent to the area of biological membrane. 8. The method of claim 1, wherein the step of continuously analyzing the at least one analyte comprises: providing the receiver with at least one reagent that facilitates the measurement of analyte flux for the at least one analyte. 9. The method of claim 1, wherein the step of continuously analyzing the at least one analyte comprises: using a method selected from the group consisting of electrochemical, biochemical, optical, fluorescence, absorbance, reflectance, Raman, magnetic, mass spectrometry, IR spectroscopy measurement methods, and combinations thereof to measure analyte flux for the at least one analyte. 10. The method of claim 1, wherein the step of continuously analyzing the at least one analyte comprises: providing a meter to analyze the at least one analyte using a method selected from the group consisting of electrochemical, optical, fluorescence, absorbance, reflectance, Raman, magnetic mass spectrometry, IR spectroscopy measurement methods, and combinations therof. 11. The method of claim 1, wherein the step of continuously analyzing the at least one analyte at least comprises: determining an analyte flux for the at least one analyte from the body fluid. 12. The method of claim 1, wherein the step of providing the results of the step of analyzing the at least one analyte comprises: displaying the results of the step of analyzing the at least one analyte. 13. The method of claim 1, wherein said analyte is glucose. 14. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of the area of biological membrane and into the receiver; providing an external force to enhance the extraction of the at least ne analyte; analyzing the at least one analyte; and providing the results of the step of analyzing the at least one analyte; wherein the step of identifying an area of biological membrane having a permeability level comprises: providing a target identifying device to the area of biological membrane. 15. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of the area of biological membrane and into the receiver; providing an external force to enhance the extraction of the at least one analyte; analyzing the at least one analyte; providing the results of the step of analyzing the at least one analyte; providing the receiver with a second receiver, the second receiver having a concentration of the at least one analyte; and maintaining the concentration of the at least one analyte in the second receiver at a level that is lower than a concentration of the extracted at least one analyte. 16. The method of claim 15, further comprising the step of: providing a second external force to the second receiver. 17. The method of claim 16, wherein the first external force and the second external force differ in at least one of a type, duration, and an intensity. 18. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeabiligy level of the area of biologial membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of area of biological membrane and into the receiver; providing a first external force by generating at least one osmotic force to enhance the extraction of the at least one analyte; analyzing the at least one analyte; and providing the results of the step of analyzing the at least one analyte; wherein the step of generating at least one osmotic force to enhance the extraction of the at least one analyte comprises: regulating the at least one osmotic force with a second external force selected from the group consisting of heat, a temperature force, a pressure force, an electromotive force, mechanical agitation, ultrasound, iontophoresis, an electromagnetic force, a magnetic force, a photothermal force, a photoacoustic force, and combinations thereof. 19. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of the area of biological membrane and into the receiver; providing a first external force by generating at least one osmotic force to enhance the extraction of the at least one analyte; analyzing the at least one analyte; and providing the results of the step of analyzing the at least one analyte; wherein the step of generating at least one osmotic force to enhance the extraction of the at least one analyte comprises: manipulating at least one of an intensity of the at least one osmotic force, a duration of the at least one osmotic force, and a frequency of the at least one osmotic force with a second external force. 20. The method of claim 19, wherein the second external force is generated by a method selected from the group consisting of: applying an electric field force, applying a magnetic field force; applying an electromagnetic field force; applying a chemical; adjusting a molarity of the at least one osmotic agent; adjusting a pH level of the at least one osmotic agent; applying an ultrasonic field force; applying an electro-osmotic field force; applying a iontophoretic field force; applying an electroporatic field force; and combinations thereof. 21. A method for non-invasive body fluid samling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of the area of biological membrane and into the receiver; providing an external force to enhance the extraction of the at least one analyte; analyzing the at least one analyte; and providing the results of the step of analyzing the at least one analyte; wherein the step of analyzing the at least one analyte comprises: determining an analyte flux for the at least one analyte from the body fluid based on an analyte flux for a plurality of analytes from the body fluid. 22. A method for non-invasive body fluid sampling and analysis, comprising: identifying an area of biological membrane having a permeability level; increasing the permeability level of the area of biological membrane; contacting the area of biological membrane with a receiver; extracting at least one analyte of the body fluid through and out of the area of biological membrane and into the receiver; providing an external force to enhance the extraction of the at least one analyte; analyzing the at least one analyte; and providing the results of the step of analyzing the at least one analyte; and removing the receiver from the area of biological membrane after a predetermined condition. 23. The method of claim 22, wherein the step of removing the receiver from the area of biological membrane after a predetermined condition comprises: removing the receiver from the area of biological membrane after an amount of the at least one analyte sufficient for analysis is received in the receiver. 24. The method of claim 23, wherein the step of removing the receiver from the area of biological membrane after a predetermined condition comprises: removing the receiver from the area of biological membrane within 15 minutes after the receiver contacts the area of biological membrane. 25. The method of claim 23, wherein the step of removing the receiver from the area of biological membrane after a predetermined condition comprises: removing the receiver from the area of biological membrane within 10 minutes after the receiver contacts the area of biological membrane. 26. The method of claim 23, wherein the step of removing the receiver from the area of biological membrane after a predetermined condition comprises: removing the receiver from the area of biological membrane within 5 minutes after the receiver contacts the area of biological membrane. 27. A system for non-invasive body fluid sampling and analysis comprising: a device for measuring a permeability level of an area of biological membrane; an ultrasonic applicator that applies the ultrasound to the area of biological membrane; a controller that controls the generation of ultrasound in response to permeability measurements; a receiver that contacts the area of biological membrane and receivers at least one analyte of the body fluid through and out the area of biological membrane, the receiver comprising: a medium; and a meter that interacts with thge receiver and detects the analyte flux for the at least one analyte entering the receiver. 28. The system of claim 27, further comprising: a cartridge containing an ultrasonic coupling solution that is inserted into the ultrasound applicator. 29. The system of claim 27, wherein the ultrasonic applicator comprises: a cartridge chamber that receives the cartridge; and a solution chamber that receives the ultrasonic coupling solution from the cartridge. 30. The system of claim 27, wherein the medium comprises at least one osmotic agent and at least one of a hydrogel layer, a fluid, and a liquid. 31. The system of claim 30, wherein the osmotic agent comprises: at least one of sodium chloride, lactate and magnesium sulfate. 32. The system of claim 31, wherein the medium further comprises: at least one agent. 33. The system of claim 27, wherein the meter comprises: a processor; and a device that detects the analyte flux selected from the group consisting of: an electrochemical detector; a biochemical detector; a fluorescence detector; a reflectance detector; a Raman detector; a magnetic detector; a mass spectrometryt detector; an IR spectroscopy detector; and combinations thereof. 34. The system of claim 27, wherein the meter comprises a display that displays an analayte flux. 35. The system of claim 27, further comprising: a device that provides a first additional energy/force to the area of biological membrane. 36. The system of claim 27, further comprising: a target ring that is attached to the area of biological membrane. 37. The system of claim 36, wherein the target ring is preapplied with an adhesive. 38. The system of claim 29, wherein the meter is wearable. 39. A system for non-invasive body fluid sampling and analysis comprising: a controller that controls the generation of ultrasound; an ultrasonic applicator that applies the ultrasound to an area of biological membrane; a receiver that contracts the area of biological membrane and receives at least one analyte of the body fluid through and out of the area biological membrane, the receiver comprising: a medium; and a meter that interacts with the receiver and detects analyte flux for the at least one analyte entering the receiver; a device that provides a first additional energy/force to the area of biological membrane, and a second receiver in communication with the receiver and having a concentration of the at least one analyte; wherein the concentration of the at least one analyte in the second receiver is maintained at a level that is lover than a concentration of the at least one analyte received in the receiver. 40. The system of claim 39, further comprising: a device that provides a second additional energy/force to the receiver. 41. The system of claim 40, wherein the first additional energy/force and the second additional energy/force differ in at least one of a type, a duraton, and an intensity. 42. A method for noninvasive body fluid sampling and analysis, comprising: enhancing a permeability level of an area of biological membrane; attaching a receiver to the area of biological membrane; extracting at least one analyte through and out of the area biological membrane; receiving the at least one analyte in the receiver; and determining a flux of at least one analyte from the body fluid, based on the flux of a plurality of analaytes from the body fluid. 43. The method of claim 42, wherein the step attaching a receiver to the area of biological membrane comprises: using an adhesive to contact the receiver to the area of biological membrane. 44. The method of claim 42, wherein the step of determining a flux of at least one analyte from the body fluid comprises: using a method selected from the group consisting of electrochemical, biochemical, optical, fluorescence, absorbance, reflectance, Raman, magnetic, mass spectrometry, IR spectroscopy measurement methods, and combinations thereof to measure the flux of the at least one analyte. 45. The method of claim 42, wherein the step of determining a flux of at least one analyte from the body fluid comprises: providing a meter to analyze the at least one analyte using a method selected from the group consisting of electrochemical, biochemical, optical, fluorescence, absorbance, reflectance, Raman, magnetic, mass spectrometry, IR spectroscopy measurement methods, and combinations thereof. 46. The method of claim 43, further comprising the step of: wearing the meter. 47. The method of claim 42, wherein the step of determining a flux of at least one analyte from the body fluid comprises: continuously determining the flux for at least one analyte from the body fluid. 48. The method of claim 42, wherein the step of determining a flux of at least one analyte from the body fluid comprises: periodically determining the flux of at least one analyte from the body fluid. 49. The method of claim 42, further comprising: displaying the flux of the at least one analyte. 50. The method of claim 42, wherein the step of attaching a receiver to the area of biological comprises: attaching the receiver to the area of biological membrane for at least 24 hours. 51. The method of claim 42, wherein the step of attaching a receiver to the area of biological membrane comprises: attaching the receiver to the area of biological membrane for at least 12 hours. 52. The method of claim 42, wherein the step of attaching a receiver to the area of biological membrane comprises: attaching the receiver to the area of biological membrane for at least 6 hours. 53. The method of claim 42, wherein the step of attaching a receiver to the area of biological membrane comprises: attaching the receiver to the area of biological membrane for at least 2 hours. 54. A device for noninvasive body fluid sampling and analysis, comprising: a receiver that is adapted to be attached to an area of biological membrane with an enhanced permeability and adapted to receiver at least one analyte through and out of the area of biological membrane, the receiver comprising: a medium; and a wearable meter that measures the flux of the at least one analyte in a continuous manner, the wearable meter comprising: a processor; and a device that detects the flux of the analyte selected from the group consisting of: an electrochemcial detector, a biochemical detector; a fluorescence detector, a absorbance detector, a reflectance detector, a Raman detector; a magnetic detector; a mass spectrometry detector, IR spectroscopy detector; and combinations thereof. 55. The device of claim 54, wherein the medium comprises: at least one osmotic agent and at least one of a hydrogel layer, a fluid, and a liquid 56. The device of claim 55, wherein the osmotic agent comprises: at least one of sodium chloride, lactate, and magnesium sulfate. 57. The device of claim 55, wherein the medium further comprises: at least one agent. 58. The device of claim 54, wherein the wearable meter further comprises: a display that displays the analyte concentration in body fluid. 59. The device of claim 54, wherein the wearable meter further comprises: a display that displays an analyte concentration. 60. A receiver that is adapted to be attached to an area of biological membrane with an enhanced permeability and adapted to receive at least one analyte through and out of the area of biological membrane, the receiver comprising: a first grid; a medium layer comprising at least one agent; a membrane that induces a concentration gradient barrier for the at least one agent; a counter grid; an oxidase layer; a detection layer; and a voltage source that provides a potential difference between the first grid and the counter grid; wherein the at least one analyte flows out of or through the biological membrane to the detector layer via the first grid, the counter grid, and the oxidase layer. 61. The receiver of claim 60, wherein the medium layer comprises at least one of a hydrogel and a liquid. 62. The receiver of claim 60, wherein the at least one agent comprises an osmotic agent. 63. The receiver of claim 62, wherein the osmotic agent comprises negative and positive charged species. 64. The receiver of claim 63, wherein a concentration of the charged species can be changed with the voltage source. 65. The receiver of claim 61, wherein the oxidase layer comprises: at least one catalyst or enzyme that detect at least one analyte. 66. The receiver of claim 60, wherein the detection layer further comprises: at least one working electrode; and at least one reference electrode; wherein the at least one working electrode and the at least one reference electrode allow for the detection of the by-products of the oxidase layer to quantify a concentration of the desired analyte of detection. 67. A method for non-invasive body fluid sampling and analysis, comprising: a) identifying an area of biological membrane having a permeability level; b) increasing the permeability level of said area by applying low frequency ultrasound; c) providing a transport force to said area to extract an analyte from a body fluid through said area into a sensing zone in communication therewith; and d) continuously analyzing said analyte in said sensing zone. 68. The method of claim 67, wherein said analyte is glucose.