System, method, and device for non-invasive body fluid sampling and analysis

• US 20030100846A1
• Filed: 03/11/2002
• Published: 05/29/2003
• Est. Priority Date: 01/08/1998
• Status: Active Grant

• Current Assignee: Echo Therapeutics Incorporated
• Original Assignee: Sontra Medical, Inc. (Echo Therapeutics Incorporated)
• Inventors: Elstrom, Tuan A., Warner, Nicholas F., Kost, Joseph, Kellogg, Scott C., Custer, Linda
• Granted Patent: US 7,066,884 B2
• Time in Patent Office: Days
• US Class Current: 600/573
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150083 by vibration, e.g. ultrasound
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150755 Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/15134 Bladeless capillary blood sampling devices, i.e. devices for perforating the skin in order to obtain a blood sample but not using a blade, needle, canula, or lancet, e.g. by laser perforation, suction or pressurized fluids
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 8/00 Diagnosis using ultrasonic, sonic or infrasonic waves imaging of objects using sonar G01S15/00
• CPC Class Codes: A61M 2025/0206 where the catheter is secured by using devices worn by the patient, e.g. belts or harnesses
• CPC Class Codes: A61M 25/02 Holding devices, e.g. on the body
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

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.

Claims

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;

contacting the area of biological membrane with a receiver;

extracting body fluid through and out of the area of biological membrane;

providing an external force to enhance the body fluid extraction;

collecting the body fluid in the receiver;

analyzing the collected body fluid for the presence of at least one analyte; and

providing the results of the step of analyzing the body fluid.

2. The method of claim 1, 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.

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 range of from about 10 kHz to about 500 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:

applying ultrasound having a frequency range of from about 20 kHz to about 150 kHz to the area of biological membrane.

5. 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.

6. 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.

7. 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.

8. The method of claim 1, further comprising the steps of:

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 at least one analyte in the body fluid.

9. The method of claim 8, further comprising the step of:

providing a second external force to the second receiver.

10. The method of claim 9, wherein the first external force and the second external force differ in at least one of a type, duration, and an intensity.

11. The method of claim 1, wherein the step of providing an external force to enhance the body fluid extraction comprises:

generating at least one osmotic force to enhance the body fluid extraction.

12. The method of claim 11, wherein the step of generating at least one osmotic force to enhance the body fluid extraction comprises:

generating the at least one osmotic force by applying at least one osmotic agent to the area of biological membrane.

13. The method of claim 11, wherein the step of generating at least one osmotic force to enhance the body fluid extraction comprises:

regulating the at least one osmotic force with an 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.

14. The method of claim 11, wherein the step of generating at least one osmotic force to enhance the body fluid extraction 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 an external force.

15. The method of claim 14, wherein the 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 electroomostic field force;

applying an iontophoretic field force;

applying an electroporatic field force; and

combinations thereof.

16. The method of claim 1, wherein the step of analyzing the body fluid for the presence of at least one analyte comprises:

providing the receiver with at least one reagent to detect the at least one analyte.

17. The method of claim 1, wherein the step of analyzing the body fluid for the presence of 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 detect the presence of the at least one analyte.

18. The method of claim 1, wherein the step of analyzing the body fluid for the presence of at least one analyte comprises:

providing a meter to analyze the body fluid 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 detect the presence of the at least one analyte.

19. The method of claim 1, wherein the step of analyzing the collected body fluid for the presence of at least one analyte comprises:

periodically analyzing the collected body fluid for the presence of at least one analyte.

20. The method of claim 1, wherein the step of analyzing the collected body fluid for the presence of at least one analyte comprises:

continuously analyzing the collected body fluid for the presence of at least one analyte.

21. The method of claim 1, wherein the step of analyzing the collected body fluid for the presence of at least one analyte comprises:

determining a concentration of the at least one analyte in the body fluid.

22. The method of claim 1, wherein the step of analyzing the collected body fluid for the presence of at least one analyte comprises:

determining a concentration of the at least one analyte in the body fluid based on a concentration of a plurality of analytes in the body fluid.

23. The method of claim 1, further comprising the step of removing the receiver from the area of biological membrane after a predetermined condition.

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 after an amount of body fluid sufficient for analysis is collected in the receiver.

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 15 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 10 minutes after the receiver contacts the area of biological membrane.

27. 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.

28. The method of claim 1, wherein the step of providing the results of the step of analyzing the body fluid comprises:

displaying the results of the step of analyzing the body fluid.

29. 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 contacts the area of biological membrane and receives body fluid through and out of the area of biological membrane, the receiver comprising;

a membrane; and

a medium contained in the 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.

30. The system of claim 29, wherein the controller comprises:

a device that measures the permeability level of the area of biological membrane.

31. The system of claim 29, further comprising:

a cartridge containing an ultrasonic coupling solution that is inserted into the ultrasound applicator.

32. The system of claim 31, 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.

33. The system of claim 29, wherein the medium comprises at least one osmotic agent and at least one of a hydrogel layer, a fluid, and a liquid.

34. The system of claim 33, wherein the osmotic agent comprises:

at least one of sodium chloride, lactate, and magnesium sulfate.

35. The system of claim 33, wherein the medium further comprises:

at least one reagent.

36. The system of claim 29, wherein the meter comprises:

a processor; and

a device that detects the presence of the analyte selected from the group consisting of;

an electrochemical detector;

a biochemical detector;

a fluorescence detector;

a absorbance detector;

a reflectance detector;

a Raman detector;

a magnetic detector;

a mass spectrometry detector;

an IR spectroscopy detector; and

combinations thereof.

37. The system of claim 29, wherein the meter comprises a display that displays an analyte concentration.

38. The system of claim 29, further comprising:

a device that provides a first additional energy/force to the area of biological membrane.

39. The system of claim 29, further comprising:

a target ring that is attached to the area of biological membrane.

40. The system of claim 29, wherein the target ring is preapplied with an adhesive.

41. The system of claim 38, further comprising:

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 lower than a concentration of the at least one analyte in the body fluid.

42. The system of claim 41, further comprising:

a device that provides a second additional energy/force to the receiver.

43. The system of claim 42, wherein the first additional energy/force and the second additional energy/force differ in at least one of a type, a duration, and an intensity.

44. The system of claim 29, wherein the meter is wearable.

45. 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 a body fluid through and out of the area of biological membrane;

collecting the body fluid in the receiver; and

determining a concentration of at least one analyte in the body fluid.

46. The method of claim 45, wherein the step of attaching a receiver to the area of biological membrane comprises:

using an adhesive to contact the receiver to the area of biological membrane.

47. The method of claim 45, wherein the step of determining a concentration of at least one analyte in 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 detect the presence of the at least one analyte.

48. The method of claim 45, wherein the step of determining a concentration of at least one analyte in the body fluid comprises:

providing a meter to analyze the body fluid 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 detect the presence of the at least one analyte.

49. The method of claim 48, further comprising the step of:

wearing the meter.

50. The method of claim 45, wherein the step of determining a concentration of at least one analyte in the body fluid comprises:

continuously determining the concentration of at least one analyte in the body fluid.

51. The method of claim 45, wherein the step of determining a concentration of at least one analyte in the body fluid comprises:

periodically determining the concentration of at least one analyte in the body fluid.

52. The method of claim 45, wherein the step of determining a concentration of at least one analyte in the body fluid comprises:

determining the concentration of the at least one analyte in the body fluid based on a concentration of a plurality of analytes in the body fluid.

53. The method of claim 45, further comprising:

displaying the concentration of the at least one analyte.

54. The method of claim 45, 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 24 hours.

55. The method of claim 45, 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.

56. The method of claim 45, 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.

57. The method of claim 45, 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.

58. A device for noninvasive body fluid sampling and analysis, comprising:

a receiver that is attached to an area of biological membrane with an enhanced permeability and receives body fluid through and out of the area of biological membrane, the receiver comprising;

a membrane; and

a medium contained in the membrane; and

wearable meter that detects the presence of at least one analyte in the received body fluid and indicates a concentration of that analyte, the wearable meter comprising;

a processor; and

a device that detects the presence of the analyte selected from the group consisting of;

an electrochemical detector;

a biochemical detector;

a fluorescence detector;

a absorbance detector;

a reflectance detector;

a Raman detector;

a magnetic detector;

a mass spectrometry detector;

an IR spectroscopy detector; and

combinations thereof.

59. The device of claim 58, wherein the medium comprises:

at least one osmotic agent and at least one of a hydrogel layer, a fluid, and a liquid.

60. The device of claim 59, wherein the osmotic agent comprises:

at least one of sodium chloride, lactate, and magnesium sulfate.

61. The device of claim 59, wherein the medium further comprises:

at least one reagent.

62. The device of claim 58, wherein the wearable meter further comprises:

a display that displays an analyte concentration.

63. The device of claim 58, wherein the receiver further comprises:

a transdermal adhesive.

64. A receiver that is attached to an area of biological membrane with an enhanced permeability and receives body fluid 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 body fluid flows out of or through the biological membrane to the detector layer via the first grid, the counter grid, and the oxidase layer.

65. The receiver of claim 64, wherein the body fluid comprises at least one of blood, interstitial fluid, analyte, and lymph.

66. The receiver of claim 64, wherein the medium layer comprises at least one of a hydrogel and a liquid.

67. The receiver of claim 64, wherein the at least one agent comprises an osmotic agent.

68. The receiver of claim 67, wherein the osmotic agent comprises negative and positive charged species.

69. The receiver of claim 68, wherein a concentration of the charged species can be changed with the voltage source.

70. The receiver of claim 64, wherein the oxidase layer comprises:

at least one catalyst or enzyme that to detect at least one analyte.

71. The receiver of claim 64, 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.