Systems and methods for collecting tear film and measuring tear film osmolarity

• US 8,713,997 B2
• Filed: 09/01/2010
• Issued: 05/06/2014
• Est. Priority Date: 03/25/2003
• Status: Active Grant

• Current Assignee: TearLab Research, Inc. (Tearlab Corp.)
• Original Assignee: TearLab Research, Inc. (Tearlab Corp.)
• Inventors: Donsky, Eric, Sullivan, Benjamin
• Primary Examiner(s): Williams, Hezron E
• Assistant Examiner(s): Frank, Rodney T
• Application Number:
  US12/874,088
• Publication Number:
  US 20110011166A1
• Time in Patent Office: 1,343 Days
• Field of Search: 73/644.7
• US Class Current: 73/64.47
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: G01N 13/04 Investigating osmotic effects
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 2201/06113 Coherent sources; lasers
• CPC Class Codes: G01N 33/487 of liquid biological material
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6854 Immunoglobulins
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

A sample receiving chip comprising a substrate that receives an aliquot volume of a sample fluid and a sample region of the substrate, sized such that the volume of the sample fluid is sufficient to operatively cover a portion of the sample region. The energy imparted into the sample fluid is transduced by the sample region to produce an output signal that indicates energy properties of the sample fluid. The sample receiving chip also includes a channel formed in the substrate, the channel configured to collect the aliquot volume of a sample fluid and transfer the aliquot volume of sample fluid to the sample region.

Claims

1. A sample receiving chip, comprising:

a. a substrate that receives a of a sample fluid, wherein the substrate is operatively shaped to receive the volume of sample fluid through capillary action,

b. a capillary channel of the substrate operatively shaped to collect the sample fluid, and

c. a sample region of the capillary channel comprising at least one transducer, wherein the sample region is configured such that the sample region is operatively covered by the sample fluid when the sample fluid is collected by the capillary channel wherein the transducer transfers energy to the sample fluid energy to produce a sample fluid reading.

2. The sample receiving chip of claim 1, wherein the substrate is formed from a hydrophilic polymer material, a resin, or glass.

3. The sample receiving chip of claim 1, wherein the capillary channel has a sinusoidal cross section, a sigmoidal cross section, a triangular cross section, a rectangular cross section, or a truncated Gaussian cross section.

4. The sample receiving chip of claim 1, wherein the capillary channel has a spatial hybrid cross section comprising two or more of the following:

sinusoidal, sigmoidal, triangular, rectangular, truncated Gaussian.

5. The sample receiving chip of claim 1, wherein the substrate is formed using a stratified stack of materials.

6. The sample receiving chip of claim 5, wherein the strata are formed from a combination of one or more hydrophilic polymers.

7. The sample receiving chip of claim 6, wherein the hydrophilic polymers comprise one or more of the following:

polyether block amides (PEBA), blockcopolyether-esters (PEE), polylactic acid (PLA), polyurethanes (PU) including aliphatic and thermoplastic polyurethanes, polyglycolic acid (PGA) and other polyesters (PE), polycaprolactone (PCL), polyethersulfones (PES), polycarbonate (PC).

8. The sample receiving chip of claim 5, wherein the strata are formed from di- and triblock copolymers.

9. The sample receiving chip of claim 8, wherein the di- and triblock copolymers are constructed with at least one of the blocks comprising amides, amines, sulfates, phosphates or other charged groups.

10. The sample receiving chip of claim 5, wherein one or more of the strata include a hydrophilic pressure sensitive adhesive.

11. The sample receiving chip of claim 5, wherein one or more of the strata are formed from glass.

12. The sample receiving chip of claim 5, wherein the strata comprise a plurality of layers that decrease in hydrophilicity.

13. The sample receiving chip of claim 5, wherein the strata comprise a hydrophilic layer sealing a less hydrophilic layer.

14. The sample receiving chip of claim 5, wherein the strata comprise a hydrophilic layer sealing a hydrophobic layer.

15. The sample receiving chip of claim 5, wherein at least one of the strata is modified to promote fluid collection.

16. The sample receiving chip of claim 5, wherein at least one of the strata is modified to lower the contact angle at the edge of the substrate.

17. The sample receiving chip of claim 5, wherein at least one of the strata is modified to lower the contact angle on the interior of the substrate.

18. The sample receiving chip of claim 5, wherein at least one of the strata is modified using one of the following:

plasma etching, acid treatment, exterior coating, and increased surface roughness.

19. The sample receiving chip of claim 1, wherein the transducer comprises a plurality of electrodes.

20. The sample receiving chip of claim 19, wherein the plurality of electrodes is arranged in a row and column array.

21. The sample receiving chip of claim 19, further comprising a plurality of conductive connection lines coupled to the plurality of electrodes, wherein the conductive connection lines provide means for transferring energy to and from the sample fluid.

22. The sample receiving chip of claim 1, wherein the sample fluid is bodily fluid.

23. The sample receiving chip of claim 22, wherein the bodily fluid is tear film.

24. The sample receiving chip of claim 1, wherein the sample fluid reading indicates osmolarity of the sample fluid.

25. The sample receiving chip of claim 1, wherein the sample fluid reading indicates the presence or amount of an analyte of interest in the sample fluid.

26. The sample receiving chip of claim 1, wherein the transducer comprises a plurality of optical indicators.

27. The sample receiving chip of claim 26, wherein the optical indicators comprise a plurality of luminescent or fluorescent nano-scale spheres.

28. The sample receiving chip of claim 1, wherein the capillary channel extends to the edge of the substrate.

29. The sample receiving chip of claim 1, wherein the capillary channel is situated within the body of the substrate.

30. The sample receiving chip of claim 1, wherein the volume of the sample fluid is less than 20 μ

L.

31. The sample receiving chip of claim 1, wherein the volume of the sample fluid is less than 100 nL.

32. The sample receiving chip of claim 1, wherein the volume of the sample fluid is 10 nL.

33. The sample receiving chip of claim 1, wherein the sample region is further configured to allow light to impart energy transfer within the transduction region.