Tunnel Junction Digital Protein Sensor for Low Concentration Detection
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Solution Overview
Problem
Current protein detection methods are limited by high concentration thresholds, requiring large sample amounts and multiple affinity reagents, making it difficult to detect proteins at low concentrations below the dissociation constant of affinity reagents.
Innovation Solution
A digital detection system using a tunnel junction device with a nanoscale device for direct electrical detection of individual molecule binding events, reducing the sample volume needed and enabling detection of minute fractions of affinity reagents, even at low concentrations, without the need for labeling or secondary probes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional protein detection methods are used, then detection can be performed with standard equipment, but the detection limit is limited to concentrations around the dissociation constant of affinity reagents (nM range)
Solution Approach 1:
The patent replaces conventional optical detection methods with direct electrical detection using a tunnel junction device. The tunnel junction measures current changes caused by single molecule binding events, eliminating the need for optical components, labels, or secondary probes. This substitution enables detection at concentrations orders of magnitude below the dissociation constant while simplifying the overall detection system architecture.
Solution Approach 2:
The affinity reagent-coated electrodes in the tunnel junction device perform dual functions: they serve as both the capture element for target molecules and the sensing element for detection. The binding event itself modulates the tunneling current, eliminating the need for separate detection mechanisms, labels, or secondary probes that would increase device complexity.
2Measurement precision
If affinity reagents with low dissociation constants are used to detect proteins at low concentrations, then detection sensitivity improves, but large amounts of sample and multiple affinity reagents are required
Solution Approach 1:
The tunnel junction device detects binding events by measuring changes in electrical current caused by the physical presence of bound molecules. This direct detection mechanism eliminates the need to concentrate samples or use multiple affinity reagents in parallel, as each binding event generates a detectable signal. The device achieves high sensitivity with minimal sample consumption by leveraging the intrinsic electrical properties of the tunnel junction.
Solution Approach 2:
The patent changes the detection parameter from optical signals (which require large sample volumes and concentration) to electrical current measurements at the single-molecule level. This parameter change enables detection of minute fractions of affinity reagents bound to target molecules, achieving high sensitivity with extremely small sample volumes (picoliter to femtoliter range).
3Quantity of substance
If large amounts of sample are used to detect low concentration proteins, then sufficient bound molecules are obtained for detection, but the sample volume requirement increases
Solution Approach 1:
The patent replaces concentration-dependent optical detection with single-molecule electrical detection. The tunnel junction measures current changes caused by individual binding events, eliminating the need to process large sample volumes to obtain sufficient bound molecules. This substitution enables detection with extremely small sample volumes by leveraging the high sensitivity of electrical measurements at the nanoscale.
Solution Approach 2:
The patent transitions from bulk solution detection to nanoscale surface detection. The tunnel junction confines the detection volume to a nanometer-scale gap between electrodes, where even a single bound molecule significantly modulates the tunneling current. This dimensional change from bulk to surface/nanoscale detection enables high sensitivity with minimal sample volume.
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 significantly lowers the detection limit for protein concentrations, allowing for the detection of single molecule binding events and reducing the sample volume required, enabling the detection of proteins at concentrations orders of magnitude below the affinity reagent's dissociation constant.
Implementation Method 1
a tunnel junction created by forming a hole in a layered tunnel junction
Data Source
AI summary
A sensing device is provided that includes a tunnel junction created by forming a hole in a layered tunnel junction (for example). A chemically, well-defined surface may be formed by coupling affinity reagents to the electrodes, which, by these means, the surface may be configured to be selective for a particular analyte.