Bioassay System Parallel Optical Detection for High-Throughput Sequencing
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Solution Overview
Problem
Conventional high-throughput nucleic acid sequencing technologies are costly, error-prone, and inefficient due to complex and expensive scanning and image analysis processes, and are limited by the number of detecting units and the distance between molecules and detectors, which hinders the goal of achieving the '$1000 genome' paradigm.
Innovation Solution
A bioassay system comprising a plurality of optical detection apparatuses that allow for parallel sequencing of multiple nucleic acid templates with a simplified design, where linker sites are proximate to light detectors, enabling direct detection of fluorophore molecules and reducing the need for complex scanning and image analysis, and allowing for single molecule sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional high-throughput capillary electrophoresis and automated genome sequencing technology are used, then sequencing throughput is increased, but device complexity and cost increase significantly
Solution Approach 1:
The system divides the detection task into many independent parallel channels, with each optical detection apparatus independently detecting a single nucleic acid molecule. This segmentation enables high throughput through parallel processing while keeping each individual detection unit simple in structure
Solution Approach 2:
The invention uses multiple copies of simple optical detection apparatuses arranged in parallel arrays. Each apparatus is an identical, simple unit that detects one molecule, and many such copies work simultaneously to achieve high throughput sequencing without requiring complex individual components
2Quantity of substance
If arrays or detection systems move to capture multiple images, then more molecules can be detected, but image acquisition and analysis time increase and errors increase
Solution Approach 1:
Instead of moving the detection system to capture multiple images sequentially, the invention inverts the approach by having multiple stationary detection apparatuses simultaneously detect multiple molecules. This eliminates the need for scanning and image tiling operations
Solution Approach 2:
The invention extracts and eliminates the complex image acquisition and analysis steps from the sequencing process. By using direct optical detection at the molecule level with stationary detectors, the system removes the need for image capturing, tiling, and alignment operations that consume time and introduce errors
3Device complexity
If existing systems that do not involve moving optics are used, then image acquisition is simplified, but the number of detecting units is limited to a modest number
Solution Approach 1:
The invention transitions from a single detection plane to a three-dimensional arrangement where multiple optical detection apparatuses are distributed in space. Each apparatus detects molecules at different positions, effectively adding spatial dimensions to the detection capacity without increasing the complexity of individual detection units
4Quantity of substance
If the distance between molecules and detecting units is increased, then more molecules can be monitored, but the strength of the detected signal decreases
Solution Approach 1:
The invention replaces mechanical scanning systems with direct optical coupling between fluorophores and photodetectors. The optical detection apparatuses are positioned in close proximity to the molecules, enabling strong signal detection through direct optical interaction without mechanical movement, while parallel arrays of such apparatuses enable monitoring of many molecules simultaneously
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
The system enables high-throughput, cost-effective, and error-reduced nucleic acid sequencing by simultaneously detecting millions of nucleic acid segments with improved signal strength, facilitating whole genome sequencing and resequencing.
Implementation Method 1
detecting a single fluorophore molecule
Implementation Method 2
light detector collects light emitted from the biomolecule
Data Source
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Figure 5
AI summary
A bioassay system is disclosed. The bioassay system may include a plurality of optical detection apparatuses, each of which includes a substrate having a light detector, and a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site. The linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers. The light detector collects light emitted from the biomolecule within a solid angle of greater than or equal to 0.8 Sl steridian. The optical detection apparatus may further include an excitation light source formed over the substrate so as to provide a light source for exciting a fluorophore attached to the biomolecule.