Multimodal In Situ Transcriptomics With Iterative Zoom and Panel Switching
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Solution Overview
Problem
Current in situ assays for biological profiling are inefficient and time-consuming, lacking the flexibility to adjust parameters and reagents between assay rounds, which limits resolution, acquisition time, and the ability to analyze multiple analytes in a sample effectively.
Innovation Solution
A multi-modal iterative in situ assay method that allows for flexible adjustment of parameters and reagents between assay rounds, enabling 'zoom in', 'zoom out', and 'switch field' capabilities, using a microscope configured for both nucleic acid sequence analysis and flexible visualization of different analytes at varying magnifications and regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current in situ assays are used for biological profiling, then spatial information of analytes can be obtained, but the analysis is inefficient and time-consuming
Solution Approach 1:
The patent divides the analysis into multiple iterative assay rounds, where each round focuses on specific analytes or regions. The microscope acquires data in segments (different fields, magnifications, or analyte panels) across multiple rounds, allowing comprehensive profiling without requiring all analytes to be analyzed simultaneously, thus improving efficiency while maintaining spatial resolution.
Solution Approach 2:
The system dynamically adjusts assay parameters between rounds based on preliminary results. The microscope can change magnification, switch between different analyte panels, and focus on specific regions of interest identified in previous rounds. This dynamic adaptation allows the system to optimize acquisition time for each round while maintaining high spatial information quality.
2Measurement precision
If current in situ assays are used for biological profiling, then spatial information of analytes can be obtained, but the acquisition time is excessive
Solution Approach 1:
The patent performs preliminary low-resolution or low-depth analysis in early assay rounds to identify regions of interest or highly relevant analytes. Based on these preliminary results, subsequent rounds focus resources on specific areas or analytes, avoiding unnecessary acquisition time spent on low-priority targets while maintaining high spatial information quality for relevant features.
Solution Approach 2:
Instead of attempting to analyze all possible analytes at maximum resolution simultaneously, the system performs partial analysis in each round, focusing on subsets of analytes or regions. Multiple partial analyses across iterative rounds achieve comprehensive coverage more efficiently than a single exhaustive analysis would require.
3Adaptability or versatility
If current in situ assays are used, then analysis of multiple analytes is attempted, but flexibility to adjust parameters and reagents between rounds is limited
Solution Approach 1:
The patent employs a universal microscope platform that can perform multiple functions across different assay rounds: it can switch between different magnifications, detect different analyte panels, and analyze different regions of the sample. This multi-functional design provides parameter adjustment flexibility without requiring separate specialized systems for each function, managing complexity through integration rather than multiplication of devices.
Solution Approach 2:
The system systematically changes assay parameters between rounds, including magnification level, analyte panel selection, and region of interest. This structured parameter variation allows flexible adaptation to different analysis needs while maintaining a consistent platform, reducing the complexity that would arise from having multiple fixed-purpose systems.
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 and flexibility of in situ analysis by reducing acquisition time and increasing resolution without compromising other parameters, allowing for high-throughput profiling of multiple biological targets with spatial information without physically isolating sample portions.
Implementation Method 1
by in situ hybridization (e.g., sequential hybridization of detection probes)
Implementation Method 2
a mode that provides the flexibility to change field, magnification, and/or channels to visualize different analytes
Data Source
AI summary
The present disclosure in some aspects relates to methods for assessing multi-modal in situ transcriptomics by combining microscopy and sequencing technologies and methods. In some aspects, the methods provided herein involve analyzing one or more analyte panels in a sample using a first imaging modality or set of imaging modalities. Based on said analysis, a different analyte panel and/or one or more different imaging modalities can be selected for subsequent analysis.