Micro-invasive method for painless detection of analytes in extracellular space

• US 8,965,470 B2
• Filed: 07/17/2008
• Issued: 02/24/2015
• Est. Priority Date: 08/20/1998
• Status: Expired due to Term

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Raskas, Eric Jules
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US12/219,228
• Publication Number:
  US 20090093693A1
• Time in Patent Office: 2,413 Days
• Field of Search: 600/309, 600/310, 600/316, 600/322, 600/344, 600/365, 600/473, 600/476
• US Class Current: 600/310
• 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 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6825 Hand
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: G01N 21/8507 Probe photometers, i.e. with optical measuring part dipped into fluid sample

Abstract

A method of detecting at least one analyte in extra-cellular spaces includes the step of inserting a microprobe through the stratum corneum toward the stratum basale of the skin of a subject into extra-cellular spaces containing interstitial fluid having at least one analyte to be detected, said microprobe having a diameter at its tip no larger than approximately 10-50 microns. The method further includes optically testing for a predetermined analyte in the extra-cellular space adjacent the distal end of the microprobe without drawing a sample of the interstitial fluid. Preferably the microprobe body includes a sensor layer covering the distal optical tip of the microprobe body, the sensor layer being adapted to interact with a predetermined analyte to be detected in the interstitial fluid, and an optical detector responsive to interaction of the sensor layer with the predetermined analyte to signal detection of said predetermined analyte.

Claims

1. An optical microprobe system for detecting at least one analyte in extra-cellular spaces comprising:

a elongate microprobe body comprising a sensor head terminating in a distal optical tip adapted to enter the stratum corneum of the skin of a subject and extend toward the stratum basale of the skin terminating in extra-cellular spaces containing interstitial fluid, the elongate microprobe body comprising a micropipette tip, the micropipette tip comprising a conical base portion having a proximal and distal end, and a conical tip portion having a proximal and distal end with a substantial step configured where the conical base portion distal end meets the conical tip portion proximal end, the conical base portion distal end having a larger diameter than the conical tip portion proximal end, to cause the microprobe tip to stop in extra cellular spaces of the skin;

a sensor layer covering the distal optical tip of the microprobe body, said sensor layer being adapted to interact with a predetermined analyte to be detected in the interstitial fluid;

an optical detector within said distal optical tip sensor head and responsive to interaction of the sensor layer with the predetermined analyte to signal detection of said predetermined analyte.

2. The system as set forth in claim 1 wherein the microprobe body distal optical tip has a diameter no larger than approximately 10-50 microns.

3. The microprobe system as set forth in claim 1 further including a computer for analyzing the signal from the optical detector to determine the concentration of said analyte.

4. The microprobe system as set forth in claim 1 further including an electrically conductive member disposed in and extending to the exterior of the distal tip, said electrically conductive member being connected to a circuit for obtaining electrochemical measurements of an analyte in the interstitial fluid.

5. The microprobe system as set forth in claim 1 further including a plurality of optical distal tips for insertion into but not through the stratum basale of the subject, each optical distal tip its own sensor layer to provide multiple tests of analyte in the interstitial fluid.

6. The microprobe system as set forth in claim 1 wherein the sensor layer is sensitive to an analyte inherently found in biological systems.

7. The microprobe system as set forth in claim 1 wherein the sensor layer is sensitive to an environmental analyte not inherently found in biological systems.

8. The optical microprobe system of claim 1, wherein the microprobe body is formed of molded silica.

9. A method of detecting at least one analyte in extra-cellular spaces comprising:

inserting an elongate microprobe sensor head comprising a micropipette tip, the micropipette tip comprising a conical base portion having a proximal end and a distal end and a conical tip portion having a proximal end and a distal end with a substantial step configured where the conical base portion distal end meets the conical tip portion proximal end, the conical base portion distal end having a larger diameter than the conical tip portion proximal end, to cause the microprobe to stop in extra cellular spaces of skin, a sensor layer covering the distal optical tip of the microprobe body, through the stratum corneum toward but not through the stratum basale of the skin of a subject into extra-cellular spaces containing interstitial fluid having at least one analyte to be detected,

activating a light source and a detector, the light source and the detector disposed within the sensor head, and

optically testing for a predetermined analyte in the extra-cellular space adjacent the distal end of the microprobe without drawing a sample of the interstitial fluid using the light source and the detector.

10. The method as set forth in claim 9 wherein said microprobe has a diameter no larger than approximately 10-50 microns.

11. The method as set forth in claim 9 wherein the microprobe is held in place with the distal end thereof in the interstitial fluid for a predetermined time, further including the step of monitoring the concentration of the analyte a plurality of times while the microprobe is held in place.

12. The method as set forth in claim 11 wherein the concentration of the analyte is continuously monitored during the time the microprobe is held in place with the distal end thereof in the interstitial fluid.

13. The method of claim 9, wherein the molding step further comprises molding the microprobe from silica.

14. The method of claim 9, wherein the molding step further comprises injection molding the microprobe.

15. The method of claim 9, wherein the molding step further comprises molding the elongate microprobe to correspond in shape to a mold having a conical base portion and a conical tip portion with a substantial step configured where the conical base portion meets the conical tip portion.