Nanoliter Tear Osmolarity Measurement via Electrical Conductivity
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Solution Overview
Problem
Current osmolarity measurement techniques for tear films are impractical in clinical settings due to their inability to accurately measure nanoliter-scale volumes, often requiring reflex tearing and being invasive, bulky, and expensive, which complicates the diagnosis of dry eye conditions like keratoconjunctivitis sicca.
Innovation Solution
A nanoliter-scale osmolarity measurement system using a microchip with printed electrodes and photolithographic techniques that measures electrical conductivity to determine osmolarity with minimal sample volume, independent of the sample volume collected, and includes a processing unit for real-time osmolarity calculation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional freezing point depression analysis is used to measure tear film osmolarity, then measurement accuracy can be achieved, but large sample volumes (20 μL) are required which cannot be obtained from KCS patients without inducing reflex tearing
Solution Approach 1:
The patent replaces the mechanical freezing point depression measurement system with an electrical conductivity-based measurement system. The microchip device uses electrical fields to measure osmolarity through conductivity changes, eliminating the need for mechanical freezing apparatus and large sample volumes. This substitution enables nanoliter-scale measurements while maintaining diagnostic accuracy.
Solution Approach 2:
The patent changes the measurement parameter from temperature-based (freezing point depression) to electrical conductivity-based. By measuring the electrical conductivity of the tear film sample, the system can determine osmolarity without requiring the sample to be frozen, thus enabling measurement of extremely small sample volumes (10-100 nL) that can be obtained from KCS patients without reflex tearing induction.
2Quantity of substance
If vapor pressure osmometry is used with filter paper absorption, then small sample volumes can be measured, but reflex tearing induction and large volume requirements make it impractical for dry eye diagnosis
Solution Approach 1:
The patent extracts the essential measurement function from complex osmometry systems and implements it directly on a miniaturized microchip platform. By integrating the measurement capability into a chip-scale device, the system eliminates the need for filter paper absorption and lengthy vapor pressure measurement processes, enabling rapid clinical testing with nanoliter samples.
Solution Approach 2:
The patent employs a disposable microchip device that can be quickly inserted and removed from the eye. The microchip is designed for single-use or limited-use scenarios, eliminating contamination risks and simplifying sterilization requirements. This disposable approach makes the procedure clinically practical and comfortable for patients with dry eye conditions.
3Productivity
If the microchip device measures electrical conductivity to determine osmolarity, then fast and non-invasive measurements with minimal sample volume are enabled, but calibration accuracy must be maintained across varying sample conditions
Solution Approach 1:
The patent implements preliminary calibration of the microchip device using known osmolarity standards before clinical use. The system includes built-in calibration protocols that establish the relationship between electrical conductivity and osmolarity under controlled conditions. This preliminary calibration ensures accurate measurements while enabling rapid subsequent testing without repeated calibration procedures.
Solution Approach 2:
The patent incorporates feedback mechanisms that monitor measurement conditions and adjust calibration parameters in real-time. The system detects variations in sample properties and automatically compensates for them by referencing stored calibration data, maintaining measurement accuracy across different clinical conditions while preserving fast measurement capabilities.
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 fast, non-invasive, and accurate osmolarity measurements with as little as 10 nanoliters of sample fluid, reducing patient risk and improving diagnostic feasibility for dry eye conditions by providing reliable osmolarity data without the need for large sample volumes or complex equipment.
Implementation Method 1
measuring the electrical conductivity of the sample fluid to determine the osmolarity of the sample fluid
Implementation Method 2
the container is brought into contact with a freezing bath or Peltier cooling device
Implementation Method 3
solutes or ions in a solvent (i.e. water), cause a lowering of the fluid freezing point from what it would be without the ions
Implementation Method 4
a thermocouple is coupled to the container and a change in voltage output from the thermocouple is measured as the sample undergoes a phase transition
Data Source
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AI summary
In accordance with the invention, a fluid sample is measured with a tear film measuring system that includes a processing device that receives a sample chip comprising a sample region configured to contain an aliquot volume of sample fluid, the processing device configured to perform analyses of osmolarity and of one or more biomarkers within the sample fluid, wherein the analysis of biomarkers includes normalization of biomarker concentration values.