Silicon microprobe with integrated biosensor

• US 7,310,543 B2
• Filed: 03/26/2001
• Issued: 12/18/2007
• Est. Priority Date: 03/26/2001
• Status: Expired due to Fees

• Current Assignee: Kumetrix Incorporated
• Original Assignee: Kumetrix Incorporated
• Inventors: Subramanian, Kumar, Smart, Wilson, Orloff, Eugene
• Primary Examiner(s): Nasser; Robert L.
• Application Number:
  US09/816,472
• Publication Number:
  US 20020137998A1
• Time in Patent Office: 2,458 Days
• Field of Search: 600345-350
• US Class Current: 600/345
• CPC Class Codes: A61B 2560/0412 Low-profile patch shaped housings
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• 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 5/6849 in combination with a needle set
• CPC Class Codes: A61B 5/685 Microneedles

Abstract

Microprobe device 10 provides an analyte signal from biosensor 12 to an external analyte meter indicating analyte presence in an analyte-containing bodily fluid of a subject (not shown).

Claims

1. A microprobe device for providing a signal to an external analyte meter indicating analyte presence in an analyte-containing bodily fluid of a subject, the microprobe device comprising:

a silicon substrate having an X length dimension and a Y width dimension and a Z thickness dimension, and having front side and a back side extending in the X and Y dimensions;

a body portion formed by the silicon substrate;

a microprobe portion formed by the silicon substrate, having a body end connected to the body portion, and having a penetration end extending away from the body portion in the X length dimension for penetrating into the subject to access the fluids; and

a biosensor integrated into the silicon substrate, for sensing analyte presence and for providing a signal in response to the analyte presence; and

a silicon microfillet portion at the connection between the body end of the microprobe portion and the body portion.

2. The device of claim 1, wherein the biosensor is an optical biosensor, an electrochemical biosensor, an electrogravimetric biosensor or a thermal biosensor.

3. The device of claim 2, further comprising a signal interface structure coupled to the biosensor.

4. The device of claim 2, wherein the signal is an electrical output signal, the device further comprising:

a signal interface structure and a signal carrier;

wherein the signal carrier includes one or more electrically conductive leads;

the signal interface structure includes one or more electrically conductive contacts.

5. The device of claim 4, wherein the interface structure is located on the surface of the body portion of the substrate, the body portion being configured to provide an electrical contact and sliding mechanical connection with an analyte meter.

6. The device of claim 1, wherein the substrate has a front surface, the biosensor is an optical biosensor or an electrochemical biosensor positioned at a location on the front surface of the body portion, the device further comprising:

an open fluid channel formed in said substrate, the fluid channel opening along said front surface from the penetration end of the microprobe portion to the location on the body portion where the biosensor is positioned for sensing analyte presence, said open fluid channel being configured to transport the analyte-containing bodily fluid to said location by capillary action.

7. The device of claim 6, wherein the open fluid channel is uncovered over the entire length of the microprobe portion.

8. The device of claim 6, wherein the penetration end terminates in a point configured to make an incision in skin, the open fluid channel being configured to transport the analyte-containing bodily fluid from the incision to the location on the body portion where the biosensor is positioned for sensing analyte presence.

9. The device of claim 1, wherein the substrate has a front surface, the biosensor is an optical biosensor or an electrochemical biosensor positioned at a location on the front surface of the body portion, the device further comprising:

an open fluid channel formed in said substrate, the fluid channel opening along said front surface from the penetration end of the microprobe portion to the location on the body portion where the biosensor is positioned for sensing analyte presence, said open fluid channel being configured to transport the analyte-containing bodily fluid to said location by capillary action; and

a cover over the body portion of the substrate;

the cover being adapted to engage a base to close said cover.

10. The device of claim 1, wherein the biosensor is on a surface on one side of the substrate, the biosensor being positioned on top of the surface on the body portion of the substrate, or on top of the surface on the microprobe portion near the body end, the device further comprising:

one or more open fluid channels, each fluid channel formed in said one side of the substrate, each of the one or more fluid channels opening along the surface of said one side from the penetration end to the biosensor, each of said one or more open fluid channels being configured to transport analyte fluid to the biosensor by capillary action.

11. The device of claim 10, wherein each of the one or more open fluid channels is uncovered over any portion that passes into the subject during penetration.

12. The device of claim 10, wherein each of the one or more open fluid channels opens along the surface of said one side from a tip of the penetration end to the biosensor.

13. The device of claim 10, wherein each of the one or more open fluid channels opens along the surface of said one side from a location at the penetration end recessed behind any area of tip formation to the biosensor.

14. The device of claim 10, wherein each of the one or more open fluid channels has a V-groove cross-section.

15. The device of claim 10, wherein each of the one or more open fluid channels has a cross-section of any shape produced by plasma etching.

16. The device of claim 10, wherein the surface on the body portion of the substrate is planar.

17. The device of claim 10, further comprising a cavity wherein the biosensor is configured to be positioned over the cavity or over the open fluid channel.

18. The device of claim 1, wherein any biosensor is located sufficiently back along the microprobe portion towards the body end that it does not come into contact with any part of the penetration end so as not to affect the sharpness of a point of the penetration end or interfere with penetration of the microprobe portion into the subject.

19. The device of claim 1, wherein the microprobe portion is width tapered along the entire the X length dimension, converging continuously from a larger Y width dimension at the body end to a smaller Y width dimension at the termination of the penetration end, wherein the rate of convergence of the microprobe taper is non-uniform for optimizing stress distribution during penetration.

20. The device of claim 1, wherein the X length of the microprobe portion is from about 0.5 mm to about 2.5 mm, and the penetration depth of the microprobe portion is from about 0.5 mm to about 2 mm.

21. The device of claim 1, wherein the X length of the body portion is from about 0.3 mm to about 2 mm, and the Y width of the body portion is from about 0.3 mm to about 2 mm.

22. The device of claim 1, wherein the Y width dimension of the microprobe portion terminates in a symmetrically shaped point at the penetration end.

23. The device of claim 1, wherein the Y width dimension of the microprobe portion terminates in a chisel shaped point at the penetration end.

24. The device of claim 1, wherein the penetration end of the microprobe portion is thinner than the body portion.

25. The device of claim 1, further comprising multiple biosensors integrated into one side of the silicon substrate, wherein any subset of the multiple biosensors is located on the body portion or on the microprobe portion near the body end, and wherein the device further comprises one or more open fluid channels in the substrate for each biosensor in the subset.

26. The device of claim 1, further comprising:

a base through the center of which the microprobe device is mounted, the base having a bottom face generally normal to said microprobe portion and a stabilizing surface applied to the bottom face.

27. The device of claim 26, further comprising:

a cover over the body portion of the substrate, the cover engaging the base for closing said cover; and

a signal transmitter configured to receive a sensed signal from the biosensor and configured to provide a transmitted electrical signal;

the signal transmitter including a source of electrical power and a signal conversion capability, said signal transmitter being located on the body portion of the substrate, the base or the cover.

28. The device of claim 26, wherein the biosensor is on the body portion of the substrate, the device further comprising:

an open fluid channel formed in the substrate, the fluid channel opening longitudinally along a surface of the substrate from the penetration end to the biosensor, said open fluid channel being configured to transport analyte fluid to the biosensor by capillary action.

29. The device of claim 1, further comprising a cover over the body portion of the substrate;

the cover being adapted to engage a base to enclose said body portion.

30. The device of claim 1, further comprising a layer on the substrate, wherein the biosensor is deposited on the layer, the layer being an electrically insulative layer.

31. A microprobe device for providing a signal to an external analyte meter indicating analyte presence in an analyte-containing bodily fluid of a subject, comprising:

a silicon substrate having an X length dimension and a Y width dimension and a Z thickness dimension, and having a front side and a back extending in the X and Y dimensions and a cavity extending into the silicon substrate in the Z thickness dimension

a body portion formed by the silicon substrate;

a microprobe portion formed by the silicon substrate, having a body end connected to the body portion, and having a penetration end extending away from the body portion in the X length dimension for penetrating into the subject to access the fluids; and

a biosensor integrated into the silicon substrate, for sensing analyte presence and for providing a signal in response to the analyte presence, the biosensor being deposited onto the silicon within the cavity.

32. The microprobe device of claim 31, wherein the cavity extends completely through the substrate in the Z thickness dimension.

33. The device of claim 32, wherein the biosensor is in the cavity and the cavity is located on the microprobe portion near the body end or the body portion;

the device further comprising;

an open fluid channel formed in one side of the substrate, the fluid channel opening along the surface of said one side from the penetration end to the biosensor, the open fluid channel being configured to transport analyte fluid to the biosensor by capillary action.

34. The microprobe device of claim 31, wherein the silicon substrate is single crystal silicon.

35. The device of claim 31, wherein the cavity is configured to vary in all three dimensions to accommodate the size of the biosensor.

36. The device of claim 31, further comprising:

a signal interface structure and a signal carrier;

wherein the biosensor is an optical biosensor responsive to the analyte presence by alterations in photon energy of the signal, the signal carrier is a photon containment structure and the interface structure is an optical coupler for interfacing with a detector.

37. The device of claim 32, wherein the biosensor is integrated into a surface of a cavity opening on a surface of one side of the substrate, the cavity extending into said one side on the microprobe portion near the body end or the body portion;

the device further comprising;

an open fluid channel formed in said one side of the substrate, the fluid channel opening along the surface of said one side from the penetration end to the biosensor, the open fluid channel being configured to transport analyte fluid to the biosensor by capillary action.

38. The device of claim 37 wherein the open fluid channel is configured to transport analyte fluid to the biosensor by capillary action without a cover over any portion of the channel that passes into the subject during penetration.

39. The device of claim 37 wherein the analyte fluid is transported from a location recessed from a portion of the penetration end forming any part of a tip.

40. The device of claim 32, wherein the biosensor is in a cavity opening on a surface of one side of the substrate, the cavity extending into said one side on the microprobe portion near the body end or the body portion, the biosensor being an electrochemical biosensor or an optical biosensor configured to provide an electrical signal indicating change in analyte concentration, the device further comprising:

an interface structure and a signal carrier on or above the surface of said one side of the substrate, the signal carrier being a pair of electrically conductive leads configured to carry the signal from the biosensor to the interface structure, the interface structure being a pair of electrically conductive contacts; and

an open fluid channel formed in said one side of the substrate, the fluid channel opening along said surface of said one side from the penetration end to the biosensor, the open fluid channel being configured to transport analyte fluid to the biosensor by capillary action.

41. A microprobe device for providing a signal to an external analyte meter indicating analyte presence in an analyte-containing bodily fluid of a subject, comprising:

a silicon substrate having an X length dimension and a Y width dimension and a Z thickness dimension, and having a front side and a back side extending in the X and Y dimensions;

a body portion formed by the silicon substrate;

a microprobe portion formed by the silicon substrate, having a body end connected to the body portion, and having a penetration end extending away from the body portion in the X length dimension for penetrating into the subject to access the fluids; and

at least one biosensor integrated into each side of the silicon substrate, for sensing analyte presence and for providing a signal in response to the analyte presence.

42. The device of claim 41 wherein any subset of the multiple biosensors is located on the body portion or on the microprobe portion near the body end, and wherein the device further comprises one or more open fluid channels in the substrate for each biosensor in the subset.