Microfluidic Tear Analysis Device for Dry Eye Diagnostics

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Solution Overview

Problem

Current methods for measuring tear osmolarity and analyzing analytes in dry eye disease are impractical due to the need for large sample volumes, induction of reflex tearing, and require skilled technicians and expensive equipment, making them unsuitable for clinical settings.

Innovation Solution

A microfluidic device that allows for simultaneous measurement of osmolarity and analyte concentration using a single device with passive or active valves for fluid control, enabling analysis of small sample volumes (10 nL to 10 μL) and integrating detection substrates for precise analyte detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ex vivo freezing point depression analysis is used to measure tear osmolarity, then diagnostic accuracy is improved, but large sample volumes (20 μL) are required which exceed the available tear volume from KCS patients

Engineering Contradiction:
Improveosmolarity measurement accuracyVSAvoidsample volume
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent replaces conventional mechanical freezing point depression apparatus with a microfluidic chip-based system that uses integrated temperature sensors and micro-scale thermal control to achieve freezing point measurement in nanoliter volumes, eliminating the need for large sample volumes while maintaining measurement accuracy

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention changes the measurement scale from microliter to nanoliter by miniaturizing the measurement chamber and adapting the thermal measurement parameters to the microfluidic environment, allowing accurate osmolarity measurement in the 10-100 nL range that is available from KCS patients

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If reflex tearing is induced to obtain sufficient tear sample volume, then sample volume is improved, but tear dilution occurs reducing diagnostic validity

Engineering Contradiction:
Improvesample volumeVSAvoidosmolarity measurement accuracy
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The microfluidic system replaces the need for reflex tearing induction by using highly sensitive nanoliter-scale measurement capabilities that can accurately measure osmolarity in the 10-100 nL volume range, allowing collection of basal tears without dilution while maintaining diagnostic accuracy

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If skilled technicians and expensive equipment are used for tear analysis, then measurement precision is improved, but device complexity and operational difficulty increase

Engineering Contradiction:
Improveanalyte detection accuracyVSAvoidequipment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges osmolarity measurement and analyte detection functions into a single integrated microfluidic chip with multiple detection zones, eliminating the need for separate expensive instruments and skilled technical operations while maintaining comprehensive diagnostic capability

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The microfluidic device achieves multi-functionality by incorporating both osmolarity sensing and multiple analyte detection capabilities in one platform, allowing a single device to perform comprehensive tear film analysis that previously required multiple specialized instruments and trained personnel

Inventive Principle:
Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables rapid, convenient, and cost-effective analysis of small fluid samples, improving diagnostic capabilities for dry eye disease and other eye conditions by minimizing sample volume requirements and eliminating the need for extensive training or expensive equipment.

Implementation Method 1

a microfluidic device that allows for simultaneous measurement of osmolarity and analyte concentration

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

The osmolarity of a sample fluid (as a non-limiting example, a tear) is determined, as a non-limiting example, by an ex vivo technique called 'freezing point depression,' in which solutes or ions in a solvent (as a non-limiting example, water), cause a lowering of the fluid freezing point

Methodology Applied
Scientific EffectFreezing point depression:

Data Source

PatentUS11536707B2Systems and methods for integration of microfluidic tear collection and lateral flow analysis of analytes of interest
Publication Date: 2022.12.27 TEARLAB RES
  • US11536707B2 patent drawing
  • US11536707B2 patent drawing
  • US11536707B2 patent drawing

AI summary

Systems, methods, and devices for analyzing small volumes of fluidic samples, as a non-limiting example, less than twenty microliters are provided. The devices are configured to make a first sample reading, for example, measure an energy property of the fluid sample, for example, osmolality, make a second sample reading, for example, detecting the presence or concentration of one or more analytes in the fluid sample, or make both the first sample reading and the second sample reading, for example, measuring the energy property of the fluid sample as well as detecting the presence or concentration of one or more analytes in the fluid sample.