Open Substrate Sequencing With Spatial Indexing and Immersion Optics
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Biological sample processing systems and methods are often inefficient and wasteful of resources, particularly in nucleic acid sequencing applications.
Innovation Solution
The use of an open substrate with immobilized analytes and controlled local environments, combined with immersion optics systems and spatial indexing, facilitates high-efficiency sample processing and analysis, including methods for nucleic acid sample processing and sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional biological sample processing systems are used, then sample analysis can be performed, but efficiency is low and resource consumption is high
Solution Approach 1:
The substrate is divided into multiple individually addressable locations (e.g., wells, positions) where different nucleic acid samples can be processed simultaneously. Each location can be independently imaged and analyzed, allowing parallel processing of multiple samples to improve throughput while using minimal reagents per sample.
Solution Approach 2:
Instead of sequencing barcodes to identify nucleic acid molecules, the system uses spatial copying - the position information of molecules on the substrate serves as a unique identifier. Multiple copies of the same sample can be loaded at different locations, and their identities are distinguished by their spatial coordinates rather than requiring additional barcode sequencing reagents.
2Loss of information
If barcode sequencing is used for nucleic acid identification, then sample origin can be determined, but additional time and resources are required
Solution Approach 1:
The identification function is extracted from the biochemical domain (barcode sequencing) and transferred to the spatial domain. The position information is directly captured during imaging without requiring additional barcode sequencing steps, thereby eliminating the time and resource overhead of barcode analysis while preserving complete sample origin information.
Solution Approach 2:
The chemical/biochemical barcode sequencing process is replaced with a spatial-mechanical identification system. The imaging system captures the physical position of nucleic acid molecules on the substrate, and this spatial information is used directly for identification, substituting the need for time-consuming barcode sequencing reactions.
3Measurement precision
If multiple nucleic acid samples are processed sequentially, then each sample can be analyzed thoroughly, but processing time increases significantly
Solution Approach 1:
Multiple nucleic acid samples are merged onto a single substrate and processed simultaneously in the same imaging field. The system captures images of all samples in parallel, maintaining complete analytical information for each sample while dramatically improving throughput by eliminating sequential processing steps.
Solution Approach 2:
The system transitions from one-dimensional sequential processing to two-dimensional parallel processing by arranging multiple samples across the substrate surface. This spatial arrangement allows simultaneous imaging and analysis of multiple samples, effectively adding a spatial dimension to the processing workflow to increase throughput without sacrificing analytical completeness.
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
Enhances the efficiency of nucleic acid sample processing and analysis by enabling rapid and resource-effective detection and identification of nucleic acid molecules without the need for barcode sequencing, using spatial indexing and immersion optics systems.
Implementation Method 1
an immersion fluid having a refractive index that matches a refractive index of the at least one optical element
Data Source
AI summary
Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate. The open substrate may be configured to rotate or otherwise move. The open substrate can comprise an array of individually addressable locations, with analytes immobilized thereto. The substrate may be spatially indexed to identify nucleic acid molecules from one or more sources, and/or sequences thereof, with the respective one or more sources. A solution comprising a plurality of probes may be directed across the array to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via scanning of the substrate while minimizing temperature fluctuations of the substrate or optical aberrations caused by bubbles.