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

• US 9,335,243 B2
• Filed: 09/11/2015
• Issued: 05/10/2016
• Est. Priority Date: 12/11/2006
• 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): Wallenhorst, Maureen
• Application Number:
  US14/852,108
• Publication Number:
  US 20150377760A1
• Time in Patent Office: 242 Days
• Field of Search: 436/63, 436/86, 436/164, 436/173, 436/174, 436/180, 436/501, 436/513, 435/7.1, 435/7.8, 435/29, 73/644.7, 356/441
• US Class Current: 1/1
• 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 including 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 method for detecting or measuring a protein of interest in tear fluid, comprising:

i) contacting a substrate with a volume of tear fluid;

ii) transferring optical energy to the volume of tear fluid; and

iii) detecting energy transfer properties of the volume of tear fluid to produce a tear fluid reading, wherein the tear fluid reading is correlated to presence or quantity of a protein of interest in the volume of tear fluid.

2. The method of claim 1, comprising detecting the energy transfer properties of the volume of tear fluid by surface plasmon resonant transduction.

3. The method of claim 1, further comprising contacting the substrate with an eye of an individual and receiving the volume of tear fluid.

4. The method of claim 1, wherein the protein of interest is a biomarker.

5. The method of claim 1, wherein the protein of interest is a protein or peptide.

6. The method of claim 1, wherein the protein of interest is an immunoglobulin, cytokine, or mucin.

7. The method of claim 6, wherein the protein of interest is lactoferrin, TGFβ

, TNFα

, interleukin 1-A, MUC5, or PRG4.

8. The method of claim 6, wherein the protein of interest is IgE, IgM, IgA, or a combination thereof.

9. The method of claim 1, wherein the volume of tear fluid is less than 20 μ

L of tear fluid.

10. The method of claim 1, wherein the volume of tear fluid is less than 100 nL of tear fluid.

11. The method of claim 1, wherein the volume of tear fluid is about 10 nL of tear fluid.

12. The method of claim 1, wherein the substrate comprises a micropipette or capillary tube.

13. The method of claim 1, wherein the substrate is part of a sample receiving chip.

14. The method of claim 1, wherein the substrate comprises a sample region sized such that the volume of the tear fluid is sufficient to operatively cover a portion of the sample region.

15. The method of claim 1, wherein the substrate comprises an adhesive.

16. The method of claim 1, wherein detecting or measuring the protein of interest comprises use of a biological substance that binds to the protein of interest.