Microfluidic Chip for Nanoliter Tear Osmolarity Measurement

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Solution Overview

Problem

Current methods for measuring osmolarity of tear films, particularly in patients with dry eye conditions, face challenges such as the need for large sample volumes, induction of reflex tearing, and user variability, making them impractical for clinical settings.

Innovation Solution

A microfluidic chip system that allows for the collection and measurement of nanoliter-scale tear samples using a substrate with electrodes and circuit connections, enabling accurate osmolarity measurement with minimal sample volume and reduced user intervention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ex vivo freezing point depression analysis is used to measure tear film osmolarity, then measurement accuracy can be achieved, but large sample volumes (1-5 μL) are required which cannot be obtained from dry eye patients without inducing reflex tearing

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

Solution Approach 1:

The invention changes the measurement parameters by developing sensors that can accurately measure osmolarity in nanoliter volumes (10-100 nL) rather than microliter volumes, enabling measurement with the small tear samples naturally present on dry eye patients' eyes without requiring reflex tearing induction

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the mechanical freezing point depression apparatus with electronic/osmotic sensors that can measure osmolarity directly in situ, eliminating the need for sample collection, transport, and laboratory analysis equipment

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

2Quantity of substance

If reflex tearing is induced to obtain sufficient tear sample volume for conventional analysis, then adequate sample volume can be collected, but the tear film becomes diluted reducing diagnostic accuracy

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

Solution Approach 1:

The invention changes the volume parameter requirement from microliters to nanoliters, allowing accurate osmolarity measurement with the small volume of tears naturally present on the ocular surface without dilution from reflex tearing

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The system utilizes the tear film already present on the patient's eye for measurement, eliminating the need for reflex tearing induction to generate additional sample volume

Inventive Principle:
Principle #25Self-service

3Measurement precision

If traditional freezing point depression osmometry is used, then osmolarity can be measured, but the procedure is complex requiring skilled technicians and hour-long calibrations

Engineering Contradiction:
Improveosmolarity measurement capabilityVSAvoidmeasurement procedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention replaces complex mechanical freezing point depression equipment with simplified electronic sensors and integrated circuits that provide rapid osmolarity readings without requiring technical expertise or lengthy calibration procedures

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

Solution Approach 2:

The invention employs disposable sensor chips or strips that are pre-calibrated and require no maintenance, eliminating the need for skilled technicians and hour-long calibrations while maintaining measurement accuracy

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Quantity of substance

If large volume tear collection is attempted from dry eye patients, then sufficient sample can be obtained for conventional analysis, but patient discomfort increases and clinical feasibility decreases

Engineering Contradiction:
Improvetear sample volumeVSAvoidclinical feasibility
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The invention changes the volume requirement from microliters to nanoliters, enabling measurement with minimal tear sample collection that causes no patient discomfort and maintains high clinical feasibility

Inventive Principle:
Principle #35Parameter changes

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 reliable, non-invasive, and accurate osmolarity measurement with minimal discomfort to patients, independent of sample volume, and requires less skill to operate, improving clinical feasibility.

Implementation Method 1

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, whereupon energy properties of the sample fluid can be detected from the sample region

Methodology Applied
Scientific EffectElectrical conduction: Conduction (electrical)

Data Source

PatentUS9335243B2Systems and methods for collecting tear film and measuring tear film osmolarity
Publication Date: 2016.05.10 TEARLAB RES
  • US9335243B2 patent drawing
  • US9335243B2 patent drawing
  • US9335243B2 patent drawing

AI summary

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.