Sparse NanoFET Array Addressing for Real-Time DNA Signal Readout
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current sequencing technologies face challenges in achieving high throughput, reducing reagent and labor costs, and improving accuracy for nucleic acid sequencing, particularly in real-time single molecule sequencing methods that do not rely on optical readouts.
Innovation Solution
The development of systems and methods using nano-electronic measurement devices, such as nanoscale field effect transistors (nanoFETs), which involve an array of devices with a polymerase enzyme complex attached to the gate, exposed to nucleotide analogs with charge labels, allowing for electrical signal monitoring to determine nucleic acid sequences through measurable changes in resistance, conductance, or impedance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical labels are used for sequencing, then detection sensitivity is improved, but system complexity and cost increase
Solution Approach 1:
The patent replaces optical detection systems with electronic detection systems. Specifically, it uses field-effect transistors (FETs) to detect nucleotide incorporation events through electrical signal changes rather than optical signals. This substitution simplifies the overall system by eliminating complex optical components while maintaining detection capability through electrical measurements of charge label positions.
2Productivity
If high throughput sequencing is achieved, then productivity increases, but reagent and labor costs increase
Solution Approach 1:
The patent segments the sequencing process into independent parallel reactions occurring on individual FET devices. Each FET can independently monitor a single nucleic acid template, allowing multiple sequences to be determined simultaneously. This segmentation enables high throughput while using minimal reagents per reaction, as each micro-scale reaction requires only trace amounts of nucleotides and enzymes.
Solution Approach 2:
The patent changes the detection parameter from optical to electrical signals. By measuring electrical properties (charge, conductance) rather than optical properties, the system achieves high throughput sequencing with reduced reagent consumption. The electrical detection method is more sensitive and requires fewer molecules to generate a detectable signal, thereby reducing reagent costs while maintaining or increasing throughput.
3Measurement precision
If real-time single molecule sequencing is performed, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent extracts and isolates single polymerase molecules and single nucleic acid templates onto individual FET devices. By separating these single molecular events from bulk reactions, the system achieves real-time monitoring with high precision. Each FET independently tracks one polymerase activity, eliminating the need for complex synchronization and data processing required in multi-molecule systems.
Solution Approach 2:
The patent replaces complex optical detection systems with simpler electronic FET-based detection. The FETs directly measure electrical signals from charge labels on nucleotides during incorporation, providing real-time data with high precision. This electronic substitution eliminates the need for complex optical components, lasers, and detectors while achieving comparable or superior measurement precision for single-molecule sequencing.
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 enables cost-effective, real-time single molecule sequencing with improved accuracy and throughput by utilizing electrical signals to identify nucleotide incorporation events, facilitating the determination of nucleic acid sequences without the need for optical labels.
Implementation Method 1
applying a voltage between the source and drain, whereby when a nucleotide analog resides in the active site of the enzyme, the charge label on the nucleotide analog produces a measurable change in the electrical signal at the gate
Data Source
AI summary
A circuit comprising a substrate with sectors on the substrate is provided, each sector comprising clock and data lines, a controller in electrical communication with the clock and data lines, a counter bias line, an amplifier input line and nano-electronic measurement devices on the substrate. A source of each device is coupled to the counter bias line and a drain of each device is coupled to the amplifier input line to obtain an electrical signal on the drain, the identity of which is determined by electrical interaction between the device and a charge label. Each device drain is gated by a corresponding switch between an on state, in which the drain is connected to the amplifier input line, and an off state, in which the drain is isolated from the amplifier input line. The controller controls switch states responsive to clock signal line pulses and data input line data.