Interferometric Liquid Volume Measurement in Microplates
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Solution Overview
Problem
Current methods for measuring liquid sample volumes in microplates are invasive, lack resolution, or require assumptions about well uniformity, making them unsuitable for accurate, non-invasive, and efficient volume determination, especially in chemical and biological laboratories.
Innovation Solution
The use of low-coherence optical interferometry provides high resolution for measuring liquid sample volumes non-invasively, accounting for the shape of the liquid meniscus and allowing for accurate, fast, and automated volume determination, suitable for various liquid types and microplate configurations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If gravimetric method is used to measure liquid volume, then measurement can be performed, but measurement time increases and static electricity/drafts/vibrations introduce substantial errors
Solution Approach 1:
The patent replaces the gravimetric method (mechanical weighing) with optical interferometry. The interferometer uses light waves to measure liquid volume by detecting optical path differences caused by refractive index variations, eliminating the need for mechanical balancing and avoiding errors from static electricity, drafts, and vibrations that affect gravimetric measurements.
Solution Approach 2:
The patent changes the measurement parameter from mass (weight) to optical properties (refractive index and optical path length). By measuring the optical characteristics of the liquid sample rather than its mass, the system achieves faster measurement without the temporal and environmental vulnerabilities of gravimetric methods.
2Measurement precision
If photometric method is used to measure liquid volume, then volume can be determined, but method requires invasive sampling and destroys sample utility for further use
Solution Approach 1:
The patent replaces photometric methods (which rely on absorbing light through the sample) with interferometric methods. Instead of having light pass through and be absorbed by the liquid, the interferometer measures optical path differences caused by refractive index variations at the liquid surface, allowing non-invasive measurement without consuming or degrading the sample.
Solution Approach 2:
The patent uses the refractive index of the liquid as an intermediary property to indirectly measure volume. Rather than directly interacting with the liquid in a consumptive way, the system measures how the liquid's optical properties affect light path length, providing a non-destructive measurement approach.
3Measurement precision
If ultrasonic ranging is used to measure liquid volume, then measurement can be performed, but resolution is insufficient for small wells in high-density microplates
Solution Approach 1:
The patent replaces ultrasonic ranging (acoustic waves) with optical interferometry. The interferometer uses light waves with much shorter wavelengths than sound waves, enabling significantly higher resolution measurements. This allows accurate measurement of small liquid volumes in high-density microplate wells where ultrasonic methods fail to provide sufficient precision.
4Measurement precision
If invasive measurement methods are used, then volume can be measured, but measurement cannot be performed non-invasively on live samples
Solution Approach 1:
The patent replaces all invasive measurement methods with optical interferometry, which measures volume by detecting optical path differences caused by refractive index variations. This non-invasive approach allows measurement of liquid volumes in live samples without physical contact or disruption to the sample, enabling volume determination in living cells and organisms.
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
This approach enables precise and efficient measurement of liquid volumes in microplates, reducing experimental errors and accommodating diverse liquid properties and microplate geometries, while being amenable to automation and computerization.
Implementation Method 1
a low-coherence optical interferometer is used to measure the liquid sample volume. The interferometer measures the volume non-invasively, quickly, and accurately.
Implementation Method 2
The interferometer measures the volume non-invasively by detecting optical path length differences caused by reflections from the liquid surface and microplate bottom interfaces.
Data Source
AI summary
An apparatus and method for the accurate and non-invasive measurement of the volume of liquid samples by optical interferometry. Small volumes of liquid samples are often contained in and partially fill the wells of a microplate. A low-coherence interferometric ranging system is used to determine the topography of the sample surface exposed by each well. The surface topography, together with the measured, or otherwise known, dimensions of the well, determine the volume of the liquid sample. Embodiment options include confining the optical beams of the interferometer to optical fiber and varying the optical-path length by piezo-electric stretching of a portion of the fiber. Other embodiment options include automation of data collection by stepping the microplate beneath the interferometer, pixelating the optical beam of the interferometer and scanning the microplate by scanning the sample beam of the interferometer with a mirror. Uniformity of the microplate wells is not required.


