Multi-camera array microscope for spatial multiomics
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Solution Overview
Problem
Current spatial biology methods lack a system for genome-wide assessment of gene expression with adequate sensitivity for quantitative studies while providing spatial context, facing challenges such as restricted RNA capture efficiency and high-resolution imaging requirements that are difficult to scale.
Innovation Solution
A multi-camera array microscope (MCAM) technology that tracks and images multiple cells over a large area, maintaining their spatial origin and viability, enabling genome-wide assessment of gene expression with high sensitivity and throughput by continuously imaging cells as they move from their original location to isolated areas for analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If physical isolation methods (laser cut of ROI) are used, then high control and experiment customization are achieved, but throughput becomes very low and the process is tedious
Solution Approach 1:
The patent segments the tissue sample into multiple regions of interest that can be independently imaged and processed. The large tissue area is divided into smaller fields of view that are captured sequentially by the microscope system, allowing parallel processing of multiple regions while maintaining customization for each region's specific analysis requirements.
Solution Approach 2:
The patent performs preliminary imaging and identification of cells and structures before physical isolation or analysis. The system captures images of the entire tissue sample first, identifies regions of interest and individual cells, then proceeds with targeted analysis or isolation, thereby streamlining the workflow and improving throughput without sacrificing customization.
2Productivity
If captured-based methods (permeabilization to extract RNA) are used, then high throughput is achieved, but single-cell resolution is not guaranteed and quantification is poor
Solution Approach 1:
The patent performs preliminary imaging to identify and locate individual cells and their spatial positions before RNA extraction and analysis. This pre-imaging step creates a spatial map that allows subsequent high-throughput processing to be accurately assigned back to specific cells, maintaining single-cell resolution throughout the workflow.
Solution Approach 2:
The patent creates optical copies (images) of the tissue sample and cell positions that can be used for tracking and spatial mapping throughout the processing workflow. These digital copies allow the system to maintain spatial information and single-cell resolution without requiring physical manipulation that would compromise cell integrity or measurement precision.
3Measurement precision
If in situ imaging methods are used, then cellular and sub-cellular resolution with good quantification are achieved, but imaging time becomes slow and the number of probes is limited
Solution Approach 1:
The patent segments the imaging task into multiple fields of view that are captured sequentially. The microscope system moves through different regions of the tissue sample, capturing images of multiple cells and structures in succession. This segmentation allows comprehensive coverage of large tissue areas while maintaining high resolution and quantification capability for each individual field of view.
Solution Approach 2:
The patent implements continuous imaging and tracking of cells throughout the workflow. Once cells are identified and tracked in initial images, the system continuously monitors their positions and maintains spatial context through subsequent processing steps, eliminating the need for repeated imaging and reducing total imaging time while preserving measurement precision.
4Quantity of substance
If genome-wide assessment methods are used, then comprehensive gene expression data is obtained, but sensitivity for quantitative studies is restricted
Solution Approach 1:
The patent performs preliminary enrichment and selection of RNA molecules before comprehensive sequencing or analysis. By using spatially-informed selection criteria and pre-enrichment steps based on initial imaging and spatial mapping, the system concentrates relevant RNA molecules, thereby improving sensitivity for quantitative studies while still enabling genome-wide assessment of gene expression.
Data Source
AI summary
An imaging system having multiple cameras providing a large field of view with sufficient resolution can be used for tracking movements of cells from their positions in a tissue sample into multiple isolated areas such as into individual microwells in a well plate. By determining the beginning and the end of the movements of each cell, the imaging system can associate the microwell locations to the original cell positions in the sample. Together with an analysis of the cells in the microwells, either individually or together with barcode beads, the analysis can achieve the spatial information needed for constructing a map of the molecular information with respect to the positions of the cells in the sample.