Fluorescence Detector Signal Conversion Circuit for DNA Sequencing
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Solution Overview
Problem
Current DNA sequencing technologies using EMCCD detectors are limited by high field rates when a large number of pixels are required, as they can only achieve high performance with a small number of pixels, and struggle to keep up with increasing reaction rates due to the limitations of CCD technology.
Innovation Solution
A detector system that uses a signal conversion circuit to generate a single pixel output signal from multiple detection elements, allowing for a large number of pixels to be read out at high field rates by identifying the detection element with the strongest signal, utilizing CMOS technology and winner take all circuits for digital pixel output and addressing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If EMCCD detectors are used for DNA sequencing, then detection sensitivity is improved, but the field rate decreases when a large number of pixels are required
Solution Approach 1:
The detector array is segmented into multiple independent detector elements (pixels), with each pixel further divided into multiple detection elements. This segmentation allows parallel processing of multiple sequencing sites while maintaining high detection sensitivity at each pixel, thereby achieving both high field rates and detection precision simultaneously.
Solution Approach 2:
The patent transitions from a single-dimension pixel array to a two-dimensional detector element arrangement within each pixel. By adding the detection element dimension within pixels, the system can process multiple signals in parallel while maintaining the sensitivity benefits of EMCCD technology, resolving the contradiction between speed and precision.
2Productivity
If the number of pixels is increased to read out more sequencing sites, then the throughput is improved, but the field rate decreases due to CCD technology limitations
Solution Approach 1:
Multiple detection elements are merged within each pixel to collectively detect fluorescence signals from multiple sequencing sites. This merging approach allows the system to maintain a high field rate by reducing the total number of pixels required, while still achieving high throughput through the combined detection capability of multiple elements per pixel.
Solution Approach 2:
Each pixel is designed to serve multiple functions by incorporating several detection elements that can simultaneously monitor different fluorescence signals. This multi-functionality allows a single pixel to handle multiple sequencing sites, increasing throughput without sacrificing field rate.
3Productivity
If reaction rates are increased to improve sequencing speed, then productivity is improved, but the detector cannot keep up with the increased reaction rates
Solution Approach 1:
The detector system is pre-configured with multiple detection elements per pixel and winner-take-all circuitry ready to handle high-rate signals. This preliminary preparation ensures that when reaction rates increase, the detector can immediately keep up without becoming a bottleneck, maintaining both productivity and reliability.
Solution Approach 2:
The patent replaces traditional CCD readout mechanics with electronic signal processing circuits (winner-take-all circuits) that can operate at much higher frequencies. This substitution eliminates the mechanical/electronic readout bottleneck, allowing the detector to reliably track increased reaction rates up to 1 kHz.
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 rapid sequencing reactions, increased throughput, and the ability to perform whole genome and gene re-sequencing quickly by enhancing the readout rate and allowing for higher concentrations of nucleotides and more parallel reactions, overcoming the speed limitations of existing CCD-based systems.
Implementation Method 1
The fluorescence in the nucleotide is effected by absorption of light at known wavelength. The fluorescence occurs at another, slightly different, known wavelength. Detection of the fluoresced light indicates the presence of a particular base.
Data Source
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AI summary
The present invention relates to a device and detector for monitoring a plurality of discrete fluorescence signals, in particular for DNA sequencing by use of fluorescently labeled nucleotides. The particular detector (118) is proposed comprising a plurality of pixels (130) for individually detecting said fluorescence signals from the plurality of fluorescent signal sources (104), wherein each pixel (130) comprises a predetermined number of at least two detection elements (D1, Dn) for detecting a received fluorescent signal and for generating detection signals. Further, a signal conversion circuit (140) is provide for receiving said detection signals from said at least two detection elements (D1, Dn) and for generating a pixel output signal indicating which of said at least two detection elements (D1, Dn) generated the strongest detection signal.