Single-Cell Lysate Splitting for Parallel RNA and Protein Analysis
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Solution Overview
Problem
Existing single-cell omics technologies provide incomplete information due to limited analysis of multiple molecular layers and rely heavily on antibody-based methods, which are biased and limited in protein analysis.
Innovation Solution
A method employing nanoSPLITS technology for parallel analysis of single cells, integrating single-cell RNA sequencing (scRNAseq) with mass spectrometry-based proteomics, using droplet microarrays to equally divide nanoliter-scale cell lysates for simultaneous mRNA and protein measurement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If single-cell omics technologies measure only one type of molecular information, then the measurement process is simple and focused, but the information completeness is insufficient
Solution Approach 1:
The patent divides the single-cell lysate into multiple portions using droplet microfluidics technology, with each portion dedicated to analyzing a specific molecular layer (transcriptome, proteome, metabolome, etc.). This segmentation enables parallel multi-omics analysis while maintaining manageable complexity for each individual analysis channel.
Solution Approach 2:
The patent employs a universal sample preparation platform that can process and divide single-cell lysates for multiple different omics analyses simultaneously. The droplet microfluidics system serves as a multi-functional device that supports various analytical techniques including RNA sequencing, mass spectrometry, and other molecular detection methods.
2Quantity of substance
If antibody-based methods are used for targeted protein measurements, then the measurement process is straightforward, but the number of proteins that can be analyzed is significantly limited
Solution Approach 1:
The patent replaces antibody-based detection with mass spectrometry technology for protein analysis. This substitution eliminates the limitation of antibody availability and enables unbiased, high-throughput quantification of thousands of proteins simultaneously, dramatically increasing the number of analyzable proteins while using a different detection mechanism.
3Reliability
If single-cell omics technologies focus on one molecular layer, then the technical protocol is simple and well-established, but the biological insight is incomplete
Solution Approach 1:
The patent merges multiple omics analysis workflows into a unified platform by dividing single-cell lysates into different portions that undergo parallel processing for transcriptomics, proteomics, metabolomics, and other molecular analyses. The results are then integrated to provide comprehensive biological insights that reflect the interconnected nature of different molecular layers.
Data Source
AI summary
Methods for performing multiple omics analysis in parallel are provided, the methods can include: dividing the mixture of cells or cell components into at least a first portion and a second portion; performing a first analysis on the first portion to acquire a first set of analytical data; performing a second analysis on the second portion to acquire a second set of analytical data. Methods for forming mixtures of analytes into first and second portions are also provided. The methods can include aligning the first and second plates to engage the first exposed surface with the second exposed surface, wherein the engaging is sufficient to convey at least some of the first analytes into the second solution to form a second mixture of the first analytes.