Transdermal sampling and analysis device

• US 9,877,673 B2
• Filed: 11/11/2011
• Issued: 01/30/2018
• Est. Priority Date: 12/10/2010
• Status: Active Grant

• Current Assignee: Cambridge Medical Technologies, LLC, Medina Isf Equity, LLC
• Original Assignee: Clinitech, LLC
• Inventors: Currie, John F., Marcanio, Joseph A., Vidalis, Joseph J., Nadarajan, Sundar B.
• Primary Examiner(s): Natnithithadha, Navin
• Assistant Examiner(s): MESSERSMITH, ERIC J
• Application Number:
  US13/294,368
• Publication Number:
  US 20120150004A1
• Time in Patent Office: 2,272 Days
• Field of Search: 20440301-40315, 600345, 600347, 600365
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/0022 Monitoring a patient using a global network, e.g. telephone networks, internet
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150076 by heating
• CPC Class Codes: A61B 5/150122 by heating
• 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 5/150412 Pointed piercing elements, e.g. needles, lancets for piercing the skin blade-like piercing elements A61B5/150442
• CPC Class Codes: A61B 5/150854 long distance, e.g. between patient's home and doctor's office
• CPC Class Codes: A61B 5/150862 intermediate range, e.g. within room or building
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150946 Means for varying, regulating, indicating or limiting the speed or time of blood collection
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• 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

Abstract

Transdermal sampling and analysis device, method and system are provided for non-invasively and transdermally obtaining biological samples from a subject and determining levels of analytes of the obtained biological samples. The transdermal sampling and analysis device, method and system may cause disruption to the skin cells to create capillary-like channels from which biological samples may flow to the transdermal sampling and analysis device. The transdermal sampling and analysis device, method and system may collect the biological samples in a reservoir where the biological sample may chemically react with a biologically reactive element. A sensor may convert the produced electrons (ions) into measured electrical signals. The converted signals may be measured and the levels of an analyte may be determined based on the measured signals.

Claims

1. A transdermal sampling and analysis device comprising:

a substrate having a first side;

a disruptor mounted on the first side of the substrate, wherein the disruptor has a resistance of about 5 Ohms to about 50 Ohms and is configured to generate a localized heat capable of altering the permeability characteristics of barrier cells of an organism to become permeable when a voltage is applied across the disruptor;

a reservoir on the first side of the transdermal sampling and analysis device, wherein the reservoir comprises;

a collection portion configured to collect and contain a biological sample that is obtained through the permeable barrier cells; and

a sensing chamber configured with a plurality of channels formed between a plurality of channel supports;

a biological sensing element comprising at least two sensing electrodes mounted on the first side of the substrate, wherein the biological sensing element is configured to determine the levels of an analyte in the biological sample;

a lid configured to enclose the reservoir and the at least two sensing electrodes within a volume formed in the reservoir;

a spacer disposed on top of the substrate; and

a lid adhesive layer adhering the lid to the spacer, wherein the lid adhesive layer has a hydrophilic wetting angle that is less than 40°

,

wherein the sensing chamber is configured to contain the biological sample around the at least two sensing electrodes, wherein the biological sample is directed over the surface of the at least two sensing electrodes by the plurality of channels.

2. The transdermal sampling and analysis device of claim 1, wherein the biological sensing element is an amperometric sensing element configured to measure a current generated across the at least two sensing electrodes carried by ions generated during a reaction between the analyte in the biological sample and a reactive agent coating the at least two sensing electrodes.

3. The transdermal sampling and analysis device of claim 1, wherein the substrate is a flexible substrate.

4. The transdermal sampling and analysis device of claim 1, wherein the substrate is made of a material selected from the group consisting of ceramic, plastic, metal and silicon.

5. The transdermal sampling and analysis device of claim 1, wherein the substrate is made of a material with a coefficient of thermal expansion (CTE) of about 10 to 50 ppm/°

C.

6. The transdermal sampling and analysis device of claim 1, wherein the substrate is made of a material with a coefficient of thermal expansion (CTE) of about 20 ppm/°

C.

7. The transdermal sampling and analysis device of claim 1, wherein the substrate is made of a material with a coefficient of thermal conductivity (CTC) of about 0.05 to 1.1 W/m°

K.

8. The transdermal sampling and analysis device of claim 1, wherein the substrate is made of a material with a CTC of about 0.12 W/m°

K.

9. The transdermal sampling and analysis device of claim 1, wherein the substrate is made from plastic.

10. The transdermal sampling and analysis device of claim 9, wherein the plastic substrate is annealed to prevent the plastic substrate from shrinking when heat is generated by the at least one disruptor mounted on the substrate.

11. The transdermal sampling and analysis device of claim 9, wherein the substrate is a polyimide.

12. The transdermal sampling and analysis device of claim 11, wherein the polyimide is Kapton™

.

13. The transdermal sampling and analysis device of claim 1, wherein the at least one disruptor is made from a material selected from the group consisting of titanium, tungsten, stainless steel, platinum and gold.

14. The transdermal sampling and analysis device of claim 1, wherein the at least one disruptor is formed in a shape selected from the group consisting of serpentine, circular, linear, square, rectangular, trapezoidal, hexagonal and triangular.

15. The transdermal sampling and analysis device of claim 14, wherein the disruptor is formed in a serpentine shape.

16. The transdermal sampling and analysis device of claim 15, wherein the coils of the serpentine disruptor are at most 20 μ

m apart.

17. The transdermal sampling and analysis device of claim 1, wherein an area covered by the at least one disruptor has a 1:

1 aspect ratio +/−

50%.

18. The transdermal sampling and analysis device of claim 14, wherein the at least one disruptor has at least one side of about 100 μ

m in length.

19. The transdermal sampling and analysis device of claim 14, wherein the at least one disruptor has at least one side of about 200 μ

m in length.

20. The transdermal sampling and analysis device of claim 14, wherein the at least one disruptor has at least one side of about 400 μ

m in length.

21. The transdermal sampling and analysis device of claim 1, wherein the at least one disruptor delivers heat at a rate of about 3 W per mm².

22. The transdermal sampling and analysis device of claim 1, wherein the at least one disruptor delivers heat at a rate of more than about 1 W per mm² and less than about 10 W per mm².

23. The transdermal sampling and analysis device of claim 1, wherein the temperature of the at least one disruptor during heating is about 50°

C to 150°

C.

24. The transdermal sampling and analysis device of claim 1, wherein the temperature of the at least one disruptor during heating is 90°

C to 110°

C.

25. The transdermal sampling and analysis device of claim 1, wherein the voltage applied across the at least one disruptor is supplied by a direct current source.

26. The transdermal sampling and analysis device of claim 1, wherein the voltage applied across the at least one disruptor reaches a voltage potential of about 2 V.

27. The transdermal sampling and analysis device of claim 26, wherein the voltage applied to the disruptor is applied in a stepwise manner until the voltage potential is reached.

28. The transdermal sampling and analysis device of claim 1, wherein the biological sensing element is a biologically reactive element.

29. The transdermal sampling and analysis device of claim 1, wherein the analyte is glucose.

30. The transdermal sampling and analysis device of claim 1, wherein the biological sensing element is an electrochemical sensor.

31. The transdermal sampling and analysis device of claim 1, wherein the at least two sensing electrodes are made from a material selected from the group consisting of platinum, carbon, silver, and gold.

32. The transdermal sampling and analysis device of claim 1, wherein the at least two sensing electrodes comprise three or more inter-digitated electrodes.

33. The transdermal sampling and analysis device of claim 32, wherein the three or more inter-digitated electrodes comprising at least one working electrode and at least one counter electrode.

34. The transdermal sampling and analysis device of claim 1, wherein the reservoir has a depth of about 20 μ

m to 70 μ

m.

35. The transdermal sampling and analysis device of claim 1, wherein the reservoir has a depth of about 50 μ

m to 70 μ

m.

36. The transdermal sampling and analysis device of claim 1, wherein the reservoir has a depth of about 30 μ

m.

37. The transdermal sampling and analysis device of claim 1, wherein a width of the plurality of channels varies along the vertical axis.

38. The transdermal sampling and analysis device of claim 1, wherein the width of each of the plurality of channels is 30 μ

m.

39. The transdermal sampling and analysis device of claim 1, wherein:

the plurality of channels comprises a first end and a second end along a horizontal axis, wherein a width of adjacent channel is successively widened such that a most narrow channel is at the first end of the plurality of channels and a most wide channel is at the second end of the plurality of channels.

40. The transdermal sampling and analysis device of claim 1, wherein each of plurality of channel supports are configured to form a contact angle of greater than 90°

when attached to the substrate.

41. The transdermal sampling and analysis device of claim 1, wherein each of the plurality of channel supports are formed from a material having a maximum wetting angle of 30°

.

42. The transdermal sampling and analysis device of claim 1, wherein the transdermal sampling and analysis device is configured to obtain a volume of biological sample through the permeable barrier cells of less than 40 nl.

43. The transdermal sampling and analysis device of claim 1, wherein the transdermal sampling and analysis device is configured to obtain a volume of biological sample through the permeable barrier cells of less than 10 nl.

44. The transdermal sampling and analysis device of claim 28, wherein the biologically reactive element is selected from the group consisting of tissues, micro-organisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, biologically derived material, bio-mimics, selective ion membranes.

45. The transdermal sampling and analysis device of claim 1, wherein the transdermal sampling and analysis device detects and measures a level of the analyte in the biological sample by using a sensing method selected from the group consisting of amperometry, coulometry, potentiometry and electrochemical impedance methods.

46. The transdermal sampling and analysis device of claim 28, wherein the biologically reactive element is selected from the group consisting of glucose oxidase and glucose dehydrogenase.

47. The transdermal sampling and analysis device of claim 1, wherein the lid is configured to expose the at least one disruptor to a user'"'"'s skin.

48. The transdermal sampling and analysis device of claim 1, wherein the lid has a thickness of about 10 μ

m to 50 μ

m.

49. The transdermal sampling and analysis device of claim 1, wherein the lid is made from a material selected from the group consisting of plastic and metal.

50. The transdermal sampling and analysis device of claim 1, wherein the spacer has a thickness of about 10 μ

m to 70 μ

m.

51. The transdermal sampling and analysis device of claim 1, wherein the lid adhesive layer has a thickness of about 5 μ

m to 20 μ

m.

52. The transdermal sampling and analysis device of claim 1, wherein the lid adhesive layer and the lid have a combined thickness of about 10 μ

m to 75 μ

m.

53. The transdermal sampling and analysis device of claim 1, wherein the lid adhesive layer has a RMS roughness value below 3 μ

m.

54. The transdermal sampling and analysis device of claim 1, wherein the lid adhesive layer has a flow characteristic T_g between 0 and 50°

C.

55. The transdermal sampling and analysis device of claim 1, wherein the sensing chamber has a volume less than 100 nl.

56. The transdermal sampling and analysis device of claim 1, wherein the sensing chamber has a volume of 10 nl.

57. The transdermal sampling and analysis device of claim 1, further comprising:

air vents coupled to the reservoir and configured to allow air contained in the reservoir to escape as the biological sample is obtained through the permeable barrier cells.

58. A system comprising:

a transdermal sampling and analysis device comprising;

a substrate having a first side;

a disruptor mounted on the first side of the substrate, wherein the disruptor has a resistance of about 5 Ohms to about 50 Ohms and is configured to generate a localized heat capable of altering the permeability characteristics of barrier cells of an organism to become permeable when a voltage is applied across the disruptor;

a reservoir on the first side of the transdermal sampling and analysis device, wherein the reservoir comprises;

a collection portion configured to collect and contain a biological sample that is obtained through the permeable barrier cells; and

a sensing chamber configured with a plurality of channels formed between a plurality of channel supports;

a biological sensing element comprising at least two sensing electrodes mounted on the first side of the substrate, wherein the biological sensing element is configured to determine the levels of an analyte in the biological sample;

a lid configured to enclose the reservoir and the at least two sensing electrodes within a volume formed in the reservoir;

a spacer disposed on top of the substrate; and

a lid adhesive layer adhering the lid to the spacer, wherein the lid adhesive layer has a hydrophilic wetting angle that is less than 40°

,

wherein the sensing chamber is configured to contain the biological sample around the at least two sensing electrodes, wherein the biological sample is directed over the surface of the at least two sensing electrodes by the plurality of channels; and

an applicator device comprising;

a housing configured to selectively engage the transdermal sampling and analysis device;

a processor, wherein the processor is coupled to the at least two sensing electrodes when the transdermal sampling and analysis device is engaged;

a display coupled to the processor;

a memory coupled to the processor; and

a voltage source coupled to the processor and for providing a voltage signal to the at least one disruptor when the transdermal sampling and analysis device is engaged, wherein the processor is configured to modify the voltage signal provided by the voltage source and apply the modified voltage signal to the at least one disruptor, and wherein the processor is configured to receive electrical signals from the at least two sensing electrodes and determine the levels of analyte present in the biological sample.

59. The system of claim 58, wherein the processor is configured to modify the voltage signal provided by the voltage source and apply the modified voltage signal to the at least one disruptor, wherein the voltage signal applied across the at least one disruptor is pulsed with a duty cycle of about 80 percent.

60. The system of claim 59, wherein a period of a completed duty cycle is 200 ms.

61. The system of claim 60, wherein the voltage signal is applied for 160 ms and turned off for 40 ms.

62. The system of claim 59, wherein the pulsed duty cycle has a frequency of about 1 Hz to 1 kHz.

63. The system of claim 59, wherein the pulsed duty cycle has a frequency of 5 Hz.

64. The system of claim 59, wherein the period of the pulses is about 0.5 sec to 5 sec.

65. The system of claim 59, wherein the voltage signal is applied for 3 sec to 20 sec.

66. The system of claim 59, wherein the voltage is applied for 3 sec to 10 sec.

67. The system of claim 58, wherein the display is configured to display the determined levels of analyte present in the biological sample.

68. The system of claim 58, wherein the applicator device further comprises a wireless transmitter configured to transmit the determined levels of analyte present in the biological sample to a remote computing device.

69. The system of claim 58, wherein the applicator device further comprises a communication port configured to transmit the determined levels of analyte present in the biological sample to a computing device via a wired connection.