Polydisperse Digital Assays for Accurate Bulk Concentration Measurement
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Solution Overview
Problem
Existing digital assays with compartments of disparate volumes face accuracy issues due to non-uniformity, leading to insufficient precision in determining bulk concentrations, and current solutions are costly, bulky, and unsuitable for on-site applications.
Innovation Solution
A system comprising a compartment-generating device, a detector, and electronic computing circuitry that generates polydisperse digital assays with compartments of varying volumes, allowing for accurate estimation of bulk concentrations using algorithms that account for the probability of multiple targets in each compartment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If digital assays use compartments of disparate volumes, then the assay can be simpler and more portable, but the measurement precision deteriorates due to non-uniformity
Solution Approach 1:
The patent changes the volume parameter of compartments from uniform to non-uniform (polydisperse) while developing a corresponding algorithm that accounts for this parameter variation. The algorithm uses the actual measured volumes of compartments to calculate bulk concentration, transforming the limitation of volume non-uniformity into an acceptable feature that enables portability while maintaining accuracy through computational correction.
Solution Approach 2:
The system incorporates feedback by measuring the actual volume of each compartment and using this information in the concentration calculation algorithm. The algorithm continuously adjusts its calculations based on the measured volume distribution, allowing the system to compensate for non-uniformity and maintain measurement precision despite using simpler, non-uniform compartment generation methods.
2Measurement precision
If monodisperse digital assays are used to ensure measurement precision, then accuracy improves, but device complexity and cost increase
Solution Approach 1:
Instead of trying to achieve uniform compartment volumes through complex generation mechanisms, the patent inverts the approach by accepting non-uniform volumes and developing algorithms that work with this reality. This inversion simplifies the hardware and assay system while maintaining accuracy through computational methods that account for volume variations.
Solution Approach 2:
The patent uses digital copying and computational modeling to represent and correct for volume non-uniformity. By creating a digital model of the compartment volume distribution and incorporating this into the calculation algorithm, the system can compensate for physical imperfections without requiring complex physical corrections, thereby reducing device complexity.
3Measurement precision
If algorithms account for multiple targets per compartment in polydisperse assays, then measurement precision improves, but computational complexity increases
Solution Approach 1:
The patent changes the mathematical approach by using probability distributions and statistical methods that naturally handle the complexity of multiple targets per compartment. By transforming the problem into a statistical estimation task using measured volumes and observed occupancy, the algorithm achieves high precision without requiring overly complex computational procedures.
Data Source
AI summary
An embodiment of a system includes a compartment-generating device, a compartment detector, and electronic computing circuitry. The device is configured to generate compartments of a digital assay, at least one of the compartments having a respective volume that is different from a respective volume of each of at least another one of the compartments. The detector is configured to determine a number of the compartments each having a respective number of a target that is greater than a threshold number of the target. And the electronic circuitry is configured to determine a bulk concentration of the target in a source of the sample in response to the determined number of compartments. Because such a system can be configured to estimate a bulk concentration of a target in a source from a polydisperse digital assay, the system can be portable, and lower-cost and faster, than conventional systems.