Non-invasive biomedical detection and monitoring systems

• US 9,986,979 B2
• Filed: 02/19/2010
• Issued: 06/05/2018
• Est. Priority Date: 02/20/2009
• Status: Active Grant

• Current Assignee: Kiffik Inc.
• Original Assignee: Invafree Hms Inc.
• Inventors: Essalik, Abdeltif, Dussault, Andr, Essalik, JalalEddine
• Primary Examiner(s): Cheng, Jacqueline
• Assistant Examiner(s): MESSERSMITH, ERIC J
• Application Number:
  US13/202,038
• Publication Number:
  US 20120041288A1
• Time in Patent Office: 3,028 Days
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• 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 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150954 Means for the detection of operative contact with patient, e.g. by temperature sensitive sensor
• 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 5/155 Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

The present disclosure relates to a non-invasive and continuous biomedical detections and non-invasive and continuous monitoring methods and devices for extracting and analyzing interstitial fluid extracted non-invasively and continuously from the skin of a subject comprising non-invasively electroporating the skin using a non pulsed voltage in combination with a pulsed voltage and applying negative pressure.

Claims

1. A method for non-invasively and continuously extracting interstitial fluid from a subject comprising the steps of:

electroporating the skin by applying a non-pulsed floor voltage 4 volt to 8 volt at a current intensity between 0.1 mA to 0.25 mA before and during an applied pulsed voltage comprised between 20 volt to 90 volt at a current intensity between 0.1 mA to 0.25 mA for a two electrodes configuration;

applying a negative pressure at or near the region of the skin being electroporated, the simultaneous combination of electroporating the skin and applying the negative pressure forming openings in the skin for extracting the interstitial fluid, the interstitial fluid being extractable only so long as the negative pressure is applied in combination with electroporating the skin; and

collecting the extracted interstitial fluid from the skin.

2. The method of claim 1, further comprising the step of analyzing the concentration of an analyte or a plurality of analytes in the interstitial fluid extracted from the skin.

3. The method of claim 1, wherein a non-pulsed voltage and a pulsed voltage are generated between at least a first moving or stationary electrode and a second stationary electrode for electroporating the skin.

4. The method of claim 2, wherein the analyte is glucose.

5. The method of claim 1, wherein said negative pressure is about 2 kPa to about 98 kPa.

6. The method of claim 2, further comprising the step of transmitting the analysis of the concentration of the analyte in the extracted interstitial fluid from the skin.

7. The method of claim 2, wherein the collecting of the interstitial fluid and the analyzing of the concentration of the analyte in the extracted interstitial fluid are regulated by a check valve.

8. The method of claim 1, wherein the negative pressure is pulsed or continuous.

9. The method of claim 1, wherein the negative pressure applied at or near the region of the skin is monitored by a pressure sensor.

10. The method of claim 1, wherein the subject is an animal or a human.

11. The method of claim 7, wherein the check valve is a one-way valve.

12. A device for non-invasively and continuously extracting interstitial fluid from the skin of a subject comprising:

an electroporator generating a non-pulsed floor voltage 4 volt to 8 volt at a current intensity between 0.1 mA to 0.25 mA before and during an applied pulsed voltage comprised between 20 volt to 90 volt at a current intensity between 0.1 mA to 0.25 mA between at least one first moving or stationary electrode and a second stationary electrode for electroporating the skin;

a vacuum pump providing a negative pressure above the skin, the vacuum pump in operation providing the negative pressure simultaneously with electroporating the skin to form openings in the skin for extracting the interstitial fluid, the interstitial fluid being extractable only so long as the negative pressure is applied in combination with electroporating the skin; and

a collecting chamber for collecting the interstitial fluid extracted from the skin.

13. The device of claim 12, wherein said collecting chamber comprises an extraction chamber for collecting the interstitial fluid extracted from the skin.

14. The device of claim 12, wherein said at least one first and second electrodes are contained in the collecting chamber.

15. The device of claim 13, wherein the extraction chamber is a separate part from the first and second electrodes used for the electroporation.

16. The device of claim 12, further comprising a biosensor or a plurality of sensors for analyzing the concentration of an analyte or a plurality of analytes in the extracted interstitial fluid from the skin.

17. The device of claim 16, wherein the biosensor or the plurality of sensors comprise an electrochemical sensor or an optical sensor.

18. The device of claim 16, wherein said biosensor or a plurality of sensors further comprise a wired or wireless communication device.

19. The device of claim 16, wherein said biosensor or plurality of sensors comprise a sensing electrode, a reference electrode and a counter electrode.

20. The device of claim 16, wherein said biosensor or a plurality of sensors comprise a sensing electrode and an accompanying electrode acting both as a reference and a counter electrode.

21. The device of claim 16, wherein said biosensor or a plurality of sensors continuously analyzes the concentration of glucose in the interstitial fluid extracted from the skin.

22. The device of claim 12, wherein said device further comprises an adhesive means for fixing the device on the skin of the subject.

23. The device of claim 22, wherein said adhesive means is a bracelet, a strap or a combination thereof.

24. The device of claim 12, wherein said device further comprises a pressure sensor for monitoring the pressure applied on the skin.

25. The device of claim 12, wherein said device further comprises a temperature sensor for monitoring the temperature of the extracted interstitial fluid.

26. The device of claim 16, wherein a valve is disposed between the biosensor and the collecting chamber creating a discontinuity between the extracted interstitial fluid and the interstitial fluid being analyzed by the biosensor.

27. The device of claim 12, wherein said pump is a peristaltic pump, a diaphragm pump, or a piston pump.

28. The device of claim 12, wherein said negative pressure generated by the pump is from about 2 kPa to about 98 kPa.

29. The device of claim 12, wherein said vacuum generated by the pump is pulsed or continuous.

30. The device of claim 16, wherein said biosensor comprises a Bis(2,2-bipyridyl)dichloro Osmium(II), complexed with poly(1-vinylimidazole) mediator in conjunction with a dispersed electronic conductor.

31. The device of claim 12, wherein said device further comprises a sampling chamber connected to the extraction chamber by a pumping conduit, said sampling chamber collects the extracted interstitial fluid from the skin for its analysis.

32. The device of claim 31, said sampling chamber is continuously sealed by a septum connected to the sampling chamber.

33. The device of claim 24, said device further comprising a microcontroller connected to the pressure sensor in order to monitor and control the pressure above the skin and inside the extraction chamber.

34. A method for electro-suturing the skin from a subject comprising the steps of:

electroporating the skin by applying a non-pulsed floor voltage 4 volt to 8 volt at a current intensity between 0.1 mA to 0.25 mA before and during an applied pulsed voltage comprised between 20 volt to 90 volt at a current intensity between 0.1 mA to 0.25 mA between two electrodes;

applying a negative pressure at or near the region of the skin being electroporated, the simultaneous combination of electroporating the skin and applying the negative pressure forming openings in the skin for suturing the skin and for extracting the interstitial fluid, the interstitial fluid being extractable only so long as the negative pressure is applied in combination with electroporating the skin; and

collecting the extracted interstitial fluid from the skin.

35. The method of claim 34, further comprising the step of analyzing the concentration of an analyte or a plurality of analytes in the interstitial fluid extracted from the skin.

36. The method of claim 34, wherein a non-pulsed voltage and a pulsed voltage are generated between at least a first moving or stationary electrode and a second stationary electrode for electroporating the skin.

37. The method of claim 35, wherein the analyte is glucose.

38. The method of claim 34, wherein said negative pressure is about 2 kPa to about 98 kPa.

39. The method of claim 35, further comprising the step of transmitting the analysis of the concentration of the analyte in the extracted interstitial fluid from the skin.

40. The method of claim 35, wherein the collecting of the interstitial fluid and the analyzing of the concentration of the analyte in the extracted interstitial fluid are regulated by a check valve.

41. The method of claim 34, wherein the negative pressure is pulsed or continuous.

42. The method of claim 34, wherein the negative pressure applied at or near the region of the skin is monitored by a pressure sensor.

43. The method of claim 34, wherein the subject is an animal or a human.

44. The method of claim 40, wherein the check valve is a one-way valve.