Bistable Polynucleotide Sensor for Multiplexed Molecular Detection
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Solution Overview
Problem
Existing high-sensitivity assays are difficult to multiplex for multiple analytes and often require series of dilution steps, leading to large sample volumes and inefficiencies in molecular event detection and quantification.
Innovation Solution
A bistable molecular sensor platform using a polynucleotide platform with a first and second shape connected by a linker, capable of switching between open and closed states in response to specific molecular events, allowing for sensitive, modular, and multiplexable detection of binding events, conformational changes, chemical modifications, or enzymatic modifications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing high-sensitivity assays are used for detection, then sensitivity is improved, but device complexity and difficulty to multiplex increase
Solution Approach 1:
The assay is divided into distinct functional modules: capture probes immobilized on the surface, target molecules in sample, and detection probes that bind to targets. Each module performs a specific function, allowing independent optimization and simplifying multiplexing by assigning different probe pairs to different targets.
Solution Approach 2:
The assay platform uses universal components that can detect multiple different analytes. The same basic mechanism (probe binding and signal generation) applies to any target, requiring only changes in probe sequences or specificities. This universal platform enables multiplexed detection without requiring separate complex systems for each analyte.
2Measurement precision
If series of dilution steps are performed for quantification, then measurement precision is improved, but loss of substance and productivity worsen
Solution Approach 1:
Capture probes are pre-immobilized on the detection surface in known quantities and positions. This preliminary preparation allows direct quantification of bound targets without requiring subsequent dilution series, as the system is already calibrated to measure target concentrations directly from the binding signal.
Solution Approach 2:
The traditional mechanical dilution process is replaced with a direct binding assay where target concentration is determined by the amount of detection probe bound to captured targets. Signal intensity or binding kinetics directly report concentration without mechanical manipulation of sample volume, eliminating material loss and reducing processing time.
3Adaptability or versatility
If existing assays are used for multiple analytes, then adaptability is improved, but device complexity and ease of operation worsen
Solution Approach 1:
Each analyte detection is implemented as a separate probe pair (capture probe + detection probe) that can be independently designed and optimized. Multiple such probe pairs are deployed simultaneously on the same platform, with each pair targeting a specific analyte. This segmentation allows high multiplexing capability while keeping each individual detection pathway simple and well-understood.
Solution Approach 2:
The platform employs a universal detection mechanism that works for all analytes: surface-immobilized capture probes, solution-phase targets, and labeled detection probes. This universal approach allows the same hardware and basic protocol to detect any number of different analytes, achieving adaptability without proportionally increasing device complexity.
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
Enables simultaneous, highly sensitive detection and quantification of multiple molecular events in small sample volumes, providing a robust platform for various applications including environmental assessment, medical diagnosis, and detection of chemical, biological, and radiological agents.
Implementation Method 1
Various molecular entities exhibit selective affinity to each other, which results in the formation of a multimolecular complex, such as a receptor-ligand, antibody-antigen, or aptamer-target complex.
Data Source
AI summary
Bistable devices are constructed using a polynucleotide platform for the sensing of 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. Devices carry DNA tags to enable separation of open and closed devices, as well as barcoding for multiplexed detection.