Microneedle arrays with ATR sensor

• US 8,160,665 B2
• Filed: 02/16/2007
• Issued: 04/17/2012
• Est. Priority Date: 02/16/2006
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Mischler, Reinhold, Werner, Gerhard
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Liu, Chu Chuan (JJ)
• Application Number:
  US11/675,725
• Publication Number:
  US 20070191696A1
• Time in Patent Office: 1,887 Days
• Field of Search: 600/316, 600/317, 600/322, 600/326, 600/327, 600/310, 600/347, 600/373, 600/573, 600/576, 604/317
• US Class Current: 600/310
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• 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 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• 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 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: G01N 21/11 Filling or emptying of cuvettes
• CPC Class Codes: G01N 21/552 Attenuated total reflection

Abstract

A sensor is described for optically determining the concentration of an analyte in a body fluid. This sensor comprises a needle arrangement which has at least one hollow needle having a hollow space extending from the distal end to the proximal end, the distal end of which is suitable for lancing. The proximal end of the needle opens into a chamber in which liquid that enters through the distal end of the needle can be collected. A window which is at least partially permeable to infrared radiation is in direct contact with the chamber.

Claims

1. A sensor for optical determination of the concentration of an analyte in a body fluid, comprising:

a needle arrangement including a plurality of needles, each needle having a distal end, a proximal end, and a hollow space extending from the distal end to the proximal end, the distal end being configured for lancing and entry of fluid;

a chamber into which the proximal end opens and in which the fluid can be collected; and

a window which is at least partially permeable to infrared radiation and is in contact with the chamber, the chamber forming an interspace between the needle arrangement and the window.

2. The sensor of claim 1, wherein the window is permeable to light of various wavelengths.

3. The sensor of claim 1, wherein the window is permeable to light having a wavelength in the range of 500-20,000 nm.

4. The sensor of claim 3, wherein the window is permeable to light having a wavelength in the range of 2000-12,000 nm.

5. The sensor of claim 1, further comprising a filter located in the needle arrangement and configured for separating molecules of greater than 10 TDa.

6. The sensor of claim 1, wherein the volume of the chamber is 1 to 1000 nl.

7. The sensor of claim 1, wherein the sensor contains no reagent which reacts with the analyte.

8. The sensor of claim 1, further comprising:

a light source configured to transmit radiation into the window;

a detector positioned on a side of the window opposite the light source and configured to generate measurement signals; and

an evaluation unit configured to calculate the concentration of an analyte from the measurement signals.

9. The sensor of claim 8, wherein the light source is configured to irradiate one side of the window and the detector is configured to capture the radiation from the opposite side of the window.

10. The sensor of claim 9, wherein the window is configured to reflect at least a portion of the light which irradiates the window.

11. The sensor of claim 8, wherein at least one of the light source and the detector is connected to the window by an optomodule.

12. The sensor of claim 8, further comprising a membrane filter incorporated into the needle arrangement.

13. A fluid sampling and analyte concentration measurement system, comprising:

a chamber in which fluid can be collected;

a plurality of needles, each needle having a distal end, a proximal end, and a hollow space extending therebetween, the distal end being configured for lancing and entry of fluid, the proximal end opening into the chamber;

a window which is at least partially permeable to infrared radiation positioned adjacent the chamber, the chamber forming an interspace between the needles and the window;

a light source configured to transmit radiation into the window;

a detector positioned on a different side of the window than the light source and configured to generate absorption measurement signals; and

an evaluation unit coupled to the detector and configured to calculate the concentration of an analyte in the fluid from the absorption measurement signals.

14. The system of claim 13, further comprising a filter disposed between the proximal end of the needles and the chamber, wherein the filter is configured to prevent molecules of greater than 10 TDa from entering the chamber.

15. The system of claim 13, wherein the chamber has a volume of 1 to 1000 nl.

16. The system of claim 13, wherein the window is permeable to light having a wavelength in the range of 500-20,000 nm.

17. The system of claim 16, wherein the window is permeable to light having a wavelength in the range of 2000-12,000 nm.

18. The system of claim 13, wherein the needles are arranged in an array.

19. The system of claim 18, wherein the window extends over substantially the entire length of the array.

20. The system of claim 19, wherein the window has a thickness in the range of about 0.025 to 0.2 mm.

21. The system of claim 20, wherein the array comprises a two-dimensional matrix.

22. The system of claim 13, wherein the window is configured for attenuated total reflection.

23. A method of determining concentration of analyte in a body fluid sample of a patient, comprising:

inserting distal ends of a plurality of needles into the patient'"'"'s skin and drawing body fluid into the needles, the needles being coupled to a chamber with a proximal end of each needle being in fluid communication with the chamber;

transferring the body fluid from the needle into the chamber, the chamber being positioned adjacent a window and forming an interspace between the needles and the window, and wherein the body fluid contacts the window;

directing light through the window;

detecting the light that passes through the window; and

determining analyte concentration from the detected light.

24. The method of claim 23, wherein the light is totally reflected several times at internal surfaces of the window before the step of detecting the light, whereby the method comprises attenuated total reflectance.

25. The method of claim 23, wherein the needles are arranged in an array.

26. The method of claim 23, wherein the directed light has a wavelength in the range of 2000 to 12,000 nm.

27. The method of claim 23, wherein the determining analyte concentration comprises continuous measurement.

28. The method of claim 27, further comprising continuously displaying the analyte concentration.

29. The method of claim 23, wherein the determining analyte concentration comprises a single measurement.

30. The method of claim 23, wherein the light comprises infrared light.

31. The method of claim 23, further comprising arranging a filter between the proximal end of the needles and the chamber and filtering high molecular weight constituents from the body fluid sample.

32. The method of claim 23, wherein the step of drawing the body fluid sample into the needles use capillary action.

33. The method of claim 23, further comprising arranging the needles, window and chamber in the form of a system and applying the system to the skin of a patient with an adhesive.

34. The method of claim 33, further comprising integrating the system into a plaster adhesive.

35. The method of claim 23, wherein the analyte concentration is determined from infrared absorption measurement, whereby reagents to react with the body fluid sample are unnecessary.

36. The method of claim 23, wherein the analyte is glucose.

37. The method of claim 23, wherein the body fluid comprises interstitial fluid.

38. The method of claim 23, further comprising providing an optomodule having a light source and a detector and coupling the optomodule to the window.

39. The method of claim 23, wherein the light directed through the window comprises monochromatic light.

40. The method of claim 23, wherein the analyte comprises one or more of glucose, creatinine, triglycerides, urea and cholesterol.

41. The method of claim 23, wherein the chamber has a volume of between 1 and 1000 nl.

42. A sensor for determining the concentration of an analyte in a body fluid, comprising:

a chamber in which fluid can be collected;

a plurality of needles, each needle having a distal end, a proximal end, and a hollow space extending therebetween, the distal end being configured for lancing and entry of body fluid, the proximal end opening into the chamber;

a window positioned adjacent the chamber and having a surface configured to contact body fluid collected in the chamber, the chamber forming an interspace between the needles and the window, the window configured for receiving radiation, reflecting the radiation from interior surfaces of the window, and transmitting the radiation from the window.

43. The sensor of claim 42, further comprising a light source positioned on one side of the window, a detector positioned on a different side of the window than the light source, and an evaluation unit coupled to the detector and configured to calculate the concentration of an analyte in the body fluid.

44. The sensor of claim 42, further comprising a filter disposed between the proximal end of the needles and the chamber, wherein the filter is configured to prevent molecules of greater than 10 TDa from entering the chamber.

45. The sensor of claim 42, wherein the chamber has a volume of 1 to 1000 nl.

46. The sensor of claim 42, wherein the window is permeable to light having a wavelength in the range of 2000-12,000 nm.

47. The sensor of claim 42, wherein the needles are arranged in an array.

48. The sensor of claim 47, wherein the window extends over substantially the entire length of the array.

49. The sensor of claim 47, wherein the window has a thickness in the range of about 0.025 to 0.2 mm.

50. The sensor of claim 42, further comprising an optomodule detachably mountable thereto, the optomodule comprising a light source configured to transmit radiation into the window, a detector configured to detect radiation that passes through the window, and an evaluation unit configured to calculate the concentration of an analyte in the body fluid.