Stochastic Sensor Arrays for Wide-Range Protein Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current single molecule measurement technologies face challenges in sensitivity due to stochastic readout noise from abundant markers, scalability issues due to concentration barriers, and limitations in multiplexing from highly selective sensors, making it difficult to detect and quantify proteins over a wide dynamic range, including ultra-low concentrations in bio-fluids.
Innovation Solution
A device comprising an array of stochastic sensors with weak interactions, DNA nanopores, and a bioprotonic conducting material, capturing electrical signals and analyzing temporal changes to determine target signatures and abundance, using DNA origami tethered DNA nanopores and a power supply to detect changes in electrical signals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single molecule measurement techniques are used to detect rare markers, then sensitivity to low concentration targets is improved, but measurement precision deteriorates due to stochastic readout noise from abundant markers
Solution Approach 1:
The invention segments the detection task by using multiple sensors with different binding affinities (strong, moderate, weak binders) to detect different concentration ranges of the same target. Each sensor type segments the dynamic range, allowing rare markers to be detected without being overwhelmed by abundant markers, as each sensor population responds optimally to different concentration thresholds.
Solution Approach 2:
The invention changes the binding affinity parameter of sensors to create a distribution of affinities across the sensor population. By incorporating sensors with varying Kd values (strong, moderate, weak binders), the system can detect targets across a wide dynamic range (10^6 fold) and distinguish rare from abundant markers based on which sensor populations are activated.
2Measurement precision
If highly selective sensors with strong binding affinities are used, then selectivity for specific markers is improved, but adaptability deteriorates as sensors can only respond to one marker type
Solution Approach 1:
The invention makes sensors universal by designing them to detect multiple different targets simultaneously. Each sensor type (strong, moderate, weak binder) can detect multiple marker types across different concentration ranges. The system achieves multiplexing by analyzing the pattern of activation across the sensor array, where different combinations of activated sensors indicate different target identities and concentrations.
Solution Approach 2:
The invention adds the dimension of binding affinity strength to the detection space. Instead of using single-affinity sensors, the system uses a distribution of affinities as an additional dimension, allowing the same sensor to potentially detect multiple targets at different concentrations and enabling differentiation of targets based on their binding characteristics across the affinity spectrum.
3Measurement precision
If additional sample preparation and filtration steps are used to increase sensitivity, then detection precision is improved, but productivity deteriorates due to reduced speed and scalability
Solution Approach 1:
The invention extracts and eliminates the need for complex sample preparation and filtration steps by using a sensor array that can directly detect targets in crude samples. The multiple affinity sensors inherently filter out noise from abundant markers through their differential activation patterns, removing the need for separate purification steps while maintaining high sensitivity for rare markers.
4Measurement precision
If conventional sensors are used to measure ultra-low concentrated samples, then measurement capability is improved, but productivity deteriorates due to concentration barriers and sensor crowding effects
Solution Approach 1:
The invention segments the concentration detection range by using sensors with different binding affinities. Strong binders detect ultra-low concentrations, moderate binders detect intermediate concentrations, and weak binders detect high concentrations. This segmentation allows the system to measure ultra-low concentrated samples quickly without suffering from sensor crowding effects, as each sensor type operates in its optimal concentration range.
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 sensitive, selective, and high-throughput molecule sensing, capable of detecting proteins over a wide dynamic range, including sub-femtomolar concentrations, directly from bio-fluid samples in real-time.
Implementation Method 1
a bioprotonic conducting material forming a planar array of protodes
Implementation Method 2
a power supply in electrical contact with each protode to provide an electric potential difference across the membrane
Implementation Method 3
the outer surface of the DNA nanopore includes one or more hydrophobic moieties
Data Source
AI summary
What is described herein is a device for sensing a target, comprising a planar array of unique stochastic sensors, wherein each sensor is weakly cross-reactive with a unique determinant on the target; a means for capturing electrical signals from each sensor and the temporal duration of each signal; and a means for analyzing the cumulative signals from the array of stochastic sensors, and optionally further comprising a computer system for processing an algorithm for identifying the target based on the electrical signals from the sensors of the device.