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Updated: Dec 22, 2025
An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing
Published on: May 23, 2018
Highly parallel and efficient single cell mRNA sequencing with paired picoliter chambers.
Mingxia Zhang1, Yuan Zou1,2, Xing Xu1
1State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China.
Paired-seq is a novel single-cell RNA sequencing platform that efficiently pairs cells with barcoded beads. This method improves RNA detection accuracy and reduces costs, making it valuable for various biological studies.
Area of Science:
- Molecular Biology
- Genomics
- Biotechnology
Background:
- Single-cell RNA sequencing (scRNA-seq) is crucial for understanding cellular heterogeneity.
- Existing bead-based scRNA-seq platforms face limitations with precious or low-cell-number samples.
- Challenges include inefficient cell utilization and contamination from cell-free RNA.
Purpose of the Study:
- To introduce Paired-seq, a novel scRNA-seq platform designed for high efficiency and cost-effectiveness.
- To overcome limitations of current platforms, particularly for scarce biological samples.
- To demonstrate Paired-seq's capability in analyzing cell heterogeneity and gene expression.
Main Methods:
- Utilizes differential flow resistance for high-efficiency single cell-barcoded bead pairing (95% utilization).
- Integrates valves and pumps to remove cell-free RNAs and optimize cell lysis and mRNA capture.
- Employs reduced reaction volumes and enhanced mRNA capture/barcoding for cost reduction.
Main Results:
- Achieves highest mRNA detection accuracy (R=0.955) with comparable sensitivity to existing methods.
- Demonstrates high cell utilization efficiency, minimizing sample loss.
- Successfully profiles single-cell expression in mouse embryonic stem cells and drug-treated cells, revealing heterogeneity.
Conclusions:
- Paired-seq offers a cost-effective, high-efficiency solution for single-cell RNA sequencing.
- The platform excels in removing cell-free RNA and achieving accurate gene detection.
- Paired-seq shows significant potential for applications in cell biology, developmental biology, and precision medicine.
