Bistable Polynucleotide Sensor for Multiplexed Molecular Detection
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Solution Overview
Problem
Current high-sensitivity assays face challenges in multiplexing for multiple analytes and require large sample volumes for quantification, limiting their ability to detect molecular events such as binding, conformational changes, and enzymatic modifications in small sample volumes.
Innovation Solution
A bistable molecular sensor platform using a polynucleotide platform with a flexible hinge or linker, immobilized on a surface, and functional molecules for optical or electronic detection, capable of changing states between open and closed configurations to detect molecular events, allowing for sensitive and modular multiplexed measurements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing high-sensitivity assays are used for quantification, then measurement precision is improved, but device complexity and difficulty of multiplexing increase
Solution Approach 1:
The sensor is divided into two distinct polynucleotide shapes (first and second shapes) that can independently bind to different analytes. This segmentation allows the single sensor to perform multiple detection functions simultaneously, enabling multiplexing while maintaining high sensitivity for each individual analyte measurement.
Solution Approach 2:
The bistable molecular sensor is designed with universal functionality to detect multiple types of molecular events including binding events, conformational changes, chemical modifications, and enzymatic modifications. The sensor can bind different analytes through various molecular interactions, making it a multi-functional platform that maintains high measurement precision across different analyte types.
2Measurement precision
If existing high-sensitivity assays are used for quantification, then measurement precision is improved, but loss of substance increases due to dilution steps
Solution Approach 1:
The bistable molecular sensor performs self-amplification through its conformational switching mechanism. When an analyte binds to the sensor, it triggers a conformational change from one state to another, which can be detected directly without requiring external amplification steps or dilution series. This self-service mechanism eliminates the need for multiple dilution steps, thereby preventing sample loss while maintaining high quantification sensitivity.
3Reliability
If surface immobilization is implemented for detection, then reliability of detection is improved, but device complexity increases
Solution Approach 1:
The sensor combines the binding function and the detection function into a single integrated structure. The same polynucleotide shapes that bind to analytes also undergo conformational changes that generate detectable signals. This merging eliminates the need for separate detection components, reducing overall device complexity while maintaining reliable detection through direct observation of binding-induced conformational changes.
4Adaptability or versatility
If modular multiplexed measurements are implemented, then adaptability is improved, but device complexity increases
Solution Approach 1:
The sensor utilizes dynamic conformational changes as the basis for detection and multiplexing. The polynucleotide shapes can dynamically switch between different conformational states in response to various analytes. This dynamic behavior allows the sensor to adapt to different analyte types and conditions without requiring complex static configurations, enabling modular multiplexed measurements while keeping the device structure relatively simple.
Data Source
AI summary
Bistable devices are constructed using a polynucleotide platform for sensing molecular events such as binding or conformational changes of target molecules. Uses include measurement of target concentration, measuring the effect of environmental condition (such as heat, light, or pH) on the target, or screening a library for molecules that bind the target or modulate its biological function. Devices comprise three regions: a top lid, bottom lid, and flexible linker or hinge between them. A device has an open configuration in which the top and bottom lid are separated, and a closed configuration they are bound close together. Binding domains or variations of the target molecule are fixed to a device so that when the molecular event occurs, the device switches from open to closed, or vice versa, which generates a signal. Optimal device design is determined by the signal modality (optical or electronic) used to measure closure of surface-immobilized devices.