Spatially Encoded Assays for High-Resolution Multiplexed Mapping
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Solution Overview
Problem
Current methods lack the ability to analyze spatial expression patterns of large numbers of genes, proteins, or other biologically active molecules simultaneously at high resolution and with high multiplexing capabilities, and existing technologies are costly and laborious.
Innovation Solution
An assay system that utilizes encoded probes delivered in defined spatial patterns, allowing interaction with biological targets, followed by separation and sequencing to determine spatial patterns of abundance or activity, enabling high-throughput digital nucleic acid sequencing for multiplexed analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods like in situ hybridization and microarrays are used for gene expression analysis, then spatial information can be obtained, but the ability to simultaneously measure large numbers of genes at multiple spatial locations is limited
Solution Approach 1:
The invention divides the biological sample into multiple discrete spatial locations or regions, assigning unique identifiers to each location. This segmentation enables simultaneous measurement of numerous genes across multiple spatial positions without sacrificing the ability to track which genes are expressed at which specific locations, thereby resolving the contradiction between measuring many genes and maintaining spatial resolution.
Solution Approach 2:
The invention adds a spatial dimension to traditional gene expression analysis by incorporating location-specific identifiers alongside gene expression data. This dimensional expansion allows the system to simultaneously capture both the identity of expressed genes and their spatial distribution across the sample, overcoming the limitation of conventional methods that can measure either many genes or spatial patterns but not both simultaneously.
2Measurement precision
If laser capture microdissection is used to analyze genes at multiple locations, then spatial information is preserved, but the method is expensive and laborious
Solution Approach 1:
The invention enables spatial mapping to occur automatically through the use of encoded probes that self-identify their location through unique molecular identifiers. Instead of requiring manual intervention to capture and analyze each spatial location, the system allows probes to autonomously carry spatial information through their encoding sequences, dramatically reducing both the cost and labor associated with spatial gene expression analysis while maintaining high spatial information accuracy.
Solution Approach 2:
The invention replaces the mechanical process of laser capture microdissection with a molecular encoding system. Instead of using laser technology to physically isolate and analyze cells at different locations, the system uses molecular identifiers embedded in probes to automatically track spatial information, eliminating the need for expensive and labor-intensive mechanical separation while preserving spatial accuracy.
3Measurement precision
If 2D PCR assays are used to preserve spatial information, then location data is maintained, but spatial resolution is low due to reliance on physical transference
Solution Approach 1:
The invention introduces molecular encoders as intermediaries between the physical tissue sample and the detection system. These encoders carry spatial information in a molecular format that can be manipulated and accessed without physically moving tissue sections, enabling high spatial resolution through molecular rather than mechanical means, and providing random access capability through sequence-based identification.
Solution Approach 2:
The invention replaces the mechanical transference of physical tissue sections between locations with a molecular encoding approach. Spatial information is captured through molecular identifiers rather than physical positioning, eliminating the resolution limitations imposed by mechanical handling while enabling random access to any spatial location through sequence-based retrieval of location information.
4Productivity
If high multiplexing is achieved through encoded probes delivered in spatial patterns, then many targets can be measured simultaneously, but the assay system complexity increases
Solution Approach 1:
The invention employs universal encoding rules and decoding algorithms that can be applied across different assay configurations and target types. This universality allows the system to handle high multiplexing capacity without proportionally increasing complexity, as the same fundamental encoding and decoding framework can accommodate varying numbers of targets and spatial locations, making the system scalable rather than requiring custom solutions for each assay condition.
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
Provides high-resolution spatial maps of biological molecules with high multiplexing capacity, allowing simultaneous measurement of multiple targets at various locations, offering efficient and cost-effective analysis of biological samples.
Implementation Method 1
allowing the encoded probes to interact with the biological targets
Data Source
AI summary
The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.