Spatial Quantum Barcoding for High-Throughput 3D Cellular Mapping
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Solution Overview
Problem
Current methods for obtaining spatial (2D or 3D) information from tissues or cells require time-consuming microscopic examination and are limited by the number of distinguishable fluorescent labels, which is typically 3-4 at a time and up to 50 with iterative staining, while isotope labeling is costly.
Innovation Solution
A method of spatially labeling targets with unique nucleic acid or protein barcodes using a sequence of subcodes, which can be assembled in situ and read by sequencing or mass-spectrometry, allowing an essentially limitless number of labels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If fluorescent labels are used for spatial localization, then the number of distinguishable labels is limited to 3-4 at a time or up to 50 with iterative staining, but the method requires time-consuming microscopic examination and has limited throughput
Solution Approach 1:
The spatial code is segmented into multiple subcodes that are assembled iteratively through sequential irradiation and subcode addition. Each subcode represents a portion of the complete spatial information, allowing the system to encode vast amounts of spatial data using simple, distinguishable molecular tags that can be read by high-throughput sequencing or mass spectrometry
Solution Approach 2:
The patent replaces the mechanical/optical system of microscopy with a molecular encoding system. Instead of using fluorescent labels that require microscopic examination, the invention uses nucleic acid or protein barcodes that can be detected by high-throughput sequencing or mass spectrometry, thereby eliminating the bottleneck of optical microscopy and enabling massive parallel processing of spatial data
2Quantity of substance
If isotope labeling is used to increase the number of labels, then up to 40 options are available, but the cost becomes very high
Solution Approach 1:
The patent uses inexpensive nucleic acid or protein molecules as disposable barcodes instead of expensive isotopic labels. These molecular tags can be synthesized at low cost and provide essentially limitless combinatorial diversity through sequence variation, eliminating the need for costly isotopic labeling while maintaining high distinguishability
3Quantity of substance
If sequential iterative staining is performed to increase the number of labels, then up to 50 labels can be achieved, but the process becomes extremely time-consuming and complex
Solution Approach 1:
The spatial information is encoded in advance through the sequential assembly of subcodes during the staining process. The iterative irradiation and subcode addition steps pre-assemble the complete spatial barcode on each target molecule, so that when the sample is later analyzed by sequencing or mass spectrometry, all spatial information is immediately available without requiring time-consuming iterative imaging steps
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
Enables high-throughput imaging of tissues or cells without microscopy, detecting DNA, RNA, and protein targets qualitatively and quantitatively, with precise spatial localization and resolution at the cellular level.
Implementation Method 1
covalently attaching an anchor to a target in the tissue sample via a reactive group
Implementation Method 2
a portion of the sample is irradiated allowing the subcode to attach to only a portion of the sample
Implementation Method 3
The subcodes attach to the anchor and the other subcodes via crosslinking
Implementation Method 4
prior to covalent attachment, the subcodes hybridize to the anchor and to the other subcodes via regions of complementarity
Implementation Method 5
The subcodes attach to the anchor and the other subcodes via sonic irradiation that facilitates a chemical reaction
Data Source
AI summary
The invention is a method of simultaneously detecting the presence and spatial location of a target in a tissue sample by attaching an anchor to the target and assembling unique positional barcodes on the anchor. The method enables analyzing cellular targets in 3D.