Interferometric Liquid Volume Measurement in Microplates
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Solution Overview
Problem
Current methods for measuring liquid sample volumes in laboratory settings are invasive, lack resolution, or require assumptions about well uniformity, making them inaccurate or impractical for precise and non-invasive volume determination, especially in microplates with varying well sizes and shapes.
Innovation Solution
A low-coherence optical interferometric system that measures the fill height of liquid samples by determining the elevation of the meniscus and using a distance calibration system to calculate the volume, accounting for the shape and dimensions of the container, allowing for accurate, non-invasive, and automated volume measurement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If photometric or fluorescent methods are used to measure liquid volume, then volume can be determined, but the method is invasive and destroys the sample
Solution Approach 1:
The patent replaces chemical/optical absorption methods (photometric/fluorescent) with mechanical displacement measurement using a balance. The volume is determined by measuring the mass of liquid dispensed and dividing by density, eliminating the need for dyes or fluorescent markers that destroy or alter the sample.
Solution Approach 2:
The patent introduces a reference liquid with known density as an intermediary to calibrate the measurement system. By measuring the mass of the reference liquid and comparing it to the mass of the sample liquid, the system can determine sample volume without directly analyzing the sample's optical properties.
2Measurement precision
If gravimetric method is used to measure liquid volume by weighing individual wells, then accurate volume can be obtained, but the process is very time consuming
Solution Approach 1:
The patent combines multiple well measurements into a single gravimetric measurement by weighing the entire microplate before and after dispensing. This allows simultaneous determination of total liquid volume across all wells, dramatically increasing throughput while maintaining accuracy through the relationship: total volume = (plate mass after - plate mass before) / liquid density.
Solution Approach 2:
The patent measures the total mass of liquid dispensed across multiple wells in one measurement rather than individually weighing each well. This partial measurement approach (measuring aggregate rather than individual components) achieves sufficient precision for most applications while vastly improving measurement speed.
3Measurement precision
If photometric method is used to measure liquid volume, then volume can be calculated from absorbance, but the method requires assumptions about well uniformity and shape
Solution Approach 1:
The patent replaces optical absorption measurements with direct gravimetric measurement. Since mass is directly proportional to volume (V = m/ρ), this eliminates the need for assumptions about well geometry, meniscus shape, or optical path uniformity that are required in photometric methods.
Solution Approach 2:
The patent changes the measurement parameter from optical absorbance (which depends on path length, concentration, and well geometry) to mass (which directly relates to volume through density). This parameter change fundamentally removes the dependencies on well uniformity and shape assumptions.
4Measurement precision
If automated liquid delivery device parameters are adjusted for different liquids, then accuracy and precision can be optimized, but the configuration process becomes complex and time consuming
Solution Approach 1:
The patent changes the measurement principle from optical methods requiring liquid-specific calibration (absorbance coefficients, fluorescence markers) to gravimetric measurement which only requires liquid density. This single parameter change (using mass instead of optical properties) dramatically simplifies the configuration process while maintaining high accuracy.
Solution Approach 2:
The gravimetric measurement system serves as a universal verification method for all liquid types without requiring liquid-specific calibration curves or markers. The same measurement principle (mass difference divided by density) applies universally across different liquids, well geometries, and dispensing volumes, eliminating the need for extensive parameter optimization for each liquid class.
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 provides high-resolution, accurate, and fast measurement of liquid volumes, suitable for microplates with varying well sizes, and is amenable to automation, overcoming the limitations of existing methods by incorporating the shape of the meniscus and container dimensions into the volume calculation.
Implementation Method 1
low-coherence optical interferometry that determines the elevation of the meniscus
Data Source
Figure 1
Figure 2
Figure 3A~3E
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.