Optical sensor for in situ measurement of analytes

• US 6,671,527 B2
• Filed: 10/12/2001
• Issued: 12/30/2003
• Est. Priority Date: 10/13/2000
• Status: Expired due to Term

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Precisense A/S (Medtronic Plc)
• Inventors: Petersson, Bo, Weber, Anders
• Primary Examiner(s): Winakur, Eric F.
• Assistant Examiner(s): McCrosky, David J.
• Application Number:
  US09/975,305
• Publication Number:
  US 20020058863A1
• Time in Patent Office: 809 Days
• Field of Search: 600/310, 600/316, 600/317, 600/347, 600/365, 424/1.17, 424/94.3, 424/533, 435/4, 435/14
• US Class Current: 600/316
• 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 5/685 Microneedles
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

An assay implantation apparatus is provided comprising a sensor for use for the in vivo measurement of an analyte and means for implanting said sensor within an upper layer of the skin from which it is naturally ejected over time by growth of the skin and progressive replacement of the outer layer of the skin.

The sensor may comprise microparticles containing a chemical assay system into which an analyte may diffuse from intercellular fluid and which assay system can be interrogated remotely by a light signal and a fluorescence sensor.

Claims

1. An assay implantation apparatus comprising:

a sensor for the in vivo measurement of an analyte; and

means for implanting said sensor within an upper layer of the skin from which the sensor is naturally ejected over time by growth of the skin and progressive replacement of the outer layer of the skin.

2. Apparatus as claimed in claim 1, wherein said implantation means comprises at least one injection needle having a length penetrable into the skin of no more than 200 μ

m.

3. Apparatus as claimed in claim 1, comprising means for projecting said sensor into the skin to penetrate to the required depth within the skin.

4. Apparatus as claimed in claim 1, wherein said sensor comprises a multitude of micro-particles, each comprising an assay for said analyte, said assay producing a readout upon interrogation which readout is an optical signal which is detectable or measurable transcutaneously by external optical means.

5. Apparatus as claimed in claim 1, wherein said assay is a binding assay, a readout of which is a detectable or measurable optical signal.

6. Apparatus as claimed in claim 5, wherein said binding assay is a competitive binding assay components of which include an analyte binding agent and an analyte analog.

7. Apparatus as claimed in claim 6, wherein said analyte analog is labelled with a first chromophore and said analyte binding agent is labelled with a second chromophore, an emission spectrum of said first chromophore overlapping with an absorption spectrum of said second chromophore.

8. Apparatus as claimed in claim 5 or claim 6, wherein the analyte binding agent is an antibody, an Fab fragment, a lectin, a hormone receptor, a drug receptor, an aptamer or a molecularly-imprinted polymer.

9. Apparatus as claimed in claim 5, wherein said detectable or measurable optical signal is generated by fluorescence resonance energy transfer, fluorescence polarisation, fluorescence quenching, phosphorescence, luminescence enhancement, luminescence quenching, diffraction or plasmon resonance.

10. Apparatus as claimed in claim 1, wherein the sensor comprises a matrix material, the components of said assay being suspended in said matrix material.

11. Apparatus as claimed in claim 1, wherein said sensor comprises solid microparticles and the components of said assay are uniformly dispersed in said solid microparticles.

12. Apparatus as claimed in claim 1, wherein said sensor comprises hollow microparticles and the components of said assay are encapsulated inside said hollow microparticles.

13. Apparatus as claimed in claim 1, wherein said sensor comprises a plurality of liposomes, the components of said assay being encapsulated inside said liposomes.

14. Apparatus as claimed in claim 1, wherein said sensor comprises a plurality of empty erythrocytes which have been loaded with the components of said assay.

15. An analytical system for the detection or quantitative measurement of an analyte in cutaneous fluid, which analytical system comprises, assay implantation apparatus as claimed in claim 1 together with optical means suitable for the transcutaneous interrogation of said sensor.

16. A method for in vivo assay of an analyte comprising:

placing a sensor within an upper layer of the skin from which the sensor is naturally ejected over time by growth of the skin and progressive replacement of the outer layer of the skin.

17. A method as claimed in claim 16, wherein the sensor is placed below the stratum corneum and within the epidermis.