Digital Microfluidic Assays With Parallel Incubation for Wide Dynamic Range
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Solution Overview
Problem
Current digital microfluidics technologies face challenges in accurately measuring a wide range of analyte concentrations in biochemical assays due to limitations in precision and linearity, particularly when dealing with high and low concentration ranges.
Innovation Solution
The method involves performing short- and long-incubation reactions in parallel on a microfluidic device, using electrowetting-mediated droplet operations, with optimized reaction protocols and negative-slope standard curves for each range to quantify analytes, and optionally including intermediate incubations, to improve precision and linearity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a single incubation protocol is used for biochemical assays, then the device complexity is low, but the measurement precision deteriorates across different analyte concentration ranges
Solution Approach 1:
The assay protocol is segmented into multiple incubation protocols (first, second, and optionally third protocols with progressively longer incubation times). Each protocol is optimized for specific analyte concentration ranges, allowing the system to achieve high measurement precision across the full dynamic range by selecting the appropriate protocol segment for each sample
Solution Approach 2:
The system dynamically selects which incubation protocol to execute based on the detected analyte concentration range. The controller automatically adjusts the incubation time and selects the appropriate standard curve based on real-time detection results, enabling the device to adapt its measurement parameters to match the sample characteristics
2Measurement precision
If multiple incubation protocols are implemented to cover different concentration ranges, then the measurement precision improves, but the productivity decreases due to additional reaction steps
Solution Approach 1:
The system dynamically determines the appropriate incubation protocol based on the detected analyte concentration range. By implementing adaptive protocol selection, the system executes only the necessary number of incubation steps for each sample - using shorter protocols for high concentration samples and longer protocols only when needed for low concentration samples, thereby maintaining high throughput while ensuring precision
Solution Approach 2:
The system uses feedback from initial detection results to determine which incubation protocol to execute next. The controller monitors the signal intensity from the first incubation protocol and uses this feedback to decide whether to proceed with additional incubation protocols, optimizing the balance between measurement precision and assay throughput based on actual sample characteristics
3Measurement precision
If longer incubation times are used to improve detection sensitivity, then the measurement precision for low concentration analytes improves, but the loss of time increases
Solution Approach 1:
The incubation time is dynamically adjusted based on the detected analyte concentration range. The system uses shorter incubation times for high concentration samples where high precision is not critical, and extends incubation time only for low concentration samples that require enhanced detection sensitivity, thereby minimizing overall time loss while maintaining precision where needed
Solution Approach 2:
The system changes the incubation time parameter adaptively based on the analyte concentration range. By implementing multiple incubation protocols with progressively longer durations and selecting the appropriate protocol based on detected concentration, the system optimizes the trade-off between detection sensitivity and time investment for each individual sample
4Productivity
If the assay is optimized for high concentration range, then the productivity is high, but the measurement precision deteriorates for low concentration analytes
Solution Approach 1:
The assay system is segmented into multiple protocols with different incubation times, where the first protocol is optimized for high concentration range (shorter incubation, higher throughput) and subsequent protocols are optimized for lower concentration ranges (longer incubation, higher precision). This segmentation allows the system to achieve both high productivity and high precision by selecting the appropriate protocol segment for each sample
Solution Approach 2:
The system dynamically transitions between different assay optimization modes based on the detected analyte concentration. For high concentration samples, the system operates in high-productivity mode with shorter incubation. When low concentration is detected, the system dynamically switches to high-precision mode with extended incubation, ensuring both productivity and precision requirements are met
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 enhances the accuracy of analyte concentration measurement across varying ranges by optimizing incubation times, reagent concentrations, and sample dilutions, thereby improving precision and linearity in biochemical assays.
Implementation Method 1
The method involves performing short- and long-incubation reactions in parallel on a microfluidic device, using electrowetting-mediated droplet operations
Data Source
AI summary
The invention relates generally to biochemical assays and more particularly to digital microfluidics multi-dynamic range parallel biochemical assays. The invention provides methods that enable improved precision and linearity for digital microfluidics analyses (i.e., analyses performed on a droplet actuator using droplet operations), including for example, assays related to measuring analytes in a biological sample. Examples of assays that may be performed using a method of the invention include measuring analytes in blood, including analytes from blood components, such as analytes present in plasma. The invention provides a digital microfluidics device (or cartridge) and methods for performing a biochemical assay using the microfluidics device to measure an analyte in a sample.