Nanotransistor Sequencing via Electrical Field Disruption
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional nucleic acid sequencing methods using optical labels are inefficient due to the need for frequent dye washing and the low probability of molecules being in close proximity to nanotransistors, making it challenging to accurately identify nucleotides and sequence molecules.
Innovation Solution
A nanotransistor-based system where a nucleic acid polymerase is tethered to a transistor, and nucleotides are labeled with moieties that induce strong field disruptions, allowing for the measurement of electrical characteristics such as current amplitude and frequency changes, enabling the identification of nucleotides without the need for optical labels or wash cycles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If optical labels and wash cycles are used for sequencing, then nucleotide identification can be achieved, but the process becomes inefficient and time-consuming
Solution Approach 1:
The patent extracts and removes the optical labeling and wash cycle components from the sequencing process. Instead of using optical labels that require washing, the invention uses nanotransistors that directly detect nucleotide incorporation through electrical signal changes, eliminating the need for time-consuming wash cycles and optical label manipulation steps
Solution Approach 2:
The patent replaces the optical detection system with an electrical detection system. Optical labels and their associated wash cycles are substituted with nanotransistor-based electrical sensing that continuously monitors nucleotide incorporation in real-time without requiring mechanical washing operations
2Reliability
If molecules are allowed to approach nanotransistors freely, then detection probability increases, but the proximity duration remains too short for accurate identification
Solution Approach 1:
The patent introduces a mediator structure that captures nucleotides and holds them in proximity to the nanotransistor. This intermediary mechanism ensures that when nucleotides approach the sensor, they are retained in the detection zone long enough for accurate electrical signal measurement, thereby increasing both detection probability and proximity duration
Solution Approach 2:
The system performs preliminary capture and positioning of nucleotides before they reach the nanotransistor detection zone. This preliminary action ensures that nucleotides are properly oriented and held in place for the required measurement duration, improving identification accuracy without requiring extended free diffusion times
3Productivity
If nanotransistors are used for sequencing, then optical labels and wash cycles are eliminated, but the probability of molecules being in close proximity remains low
Solution Approach 1:
The patent employs intermediary structures that actively capture and present nucleotides to the nanotransistor sensor. These intermediaries increase the local concentration of nucleotides near the sensor and extend their residence time in the detection zone, thereby significantly improving detection probability while maintaining the efficiency benefits of label-free electrical detection
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 increases the duration and probability of nucleotides being in proximity to the nanotransistor, enhancing the accuracy and efficiency of nucleic acid sequencing by directly measuring electrical changes, thereby improving the sequencing process.
Implementation Method 1
nucleotides are labeled with moieties that induce strong field disruptions, allowing for the measurement of electrical characteristics such as current amplitude and frequency changes
Data Source
AI summary
Embodiments may include a nucleic acid molecule system. The system may include a nucleic acid polymerase attached to a tether compound. The polymerase may be configured to elongate a nascent strand. The system may also include a nucleotide attached to a label compound. The label compound may include a moiety. The system may further include a transistor in electrical communication with a power supply. The polymer may be attached to the transistor. In addition, the system may include a meter device configured to measure an electrical characteristic of the transistor from the moiety after the label compound is cleaved from the nucleotide by the nucleic acid polymerase.