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Related Experiment Video

Updated: Aug 20, 2025

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

Published on: May 23, 2018

Combinatorial perturbation sequencing on single cells using microwell-based droplet random pairing.

Run Xie¹, Yang Liu², Shiyu Wang²

¹Department of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China; BGI-Shenzhen, Shenzhen, 518083, China.

Biosensors & Bioelectronics

|November 17, 2022

Summary

Combinatorial drug therapy can be improved with a new method called combinatorial perturbation sequencing (CP-seq). This technique enables high-throughput screening of drug combinations and their effects on single cells.

Keywords:

Droplet microfluidics Drug screening High throughput assay Single-cell RNA sequencing

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Last Updated: Aug 20, 2025

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

Published on: May 23, 2018

A Droplet-Based Microfluidic Approach and Microsphere-PCR Amplification for Single-Stranded DNA Amplicons

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Published on: November 14, 2018

Establishing Single-Cell Based Co-Cultures in a Deterministic Manner with a Microfluidic Chip

Establishing Single-Cell Based Co-Cultures in a Deterministic Manner with a Microfluidic Chip

Published on: September 27, 2019

Area of Science:

Biotechnology
Genomics
Pharmacology

Background:

Combinatorial drug therapy is crucial for overcoming drug resistance and disease relapse.
Identifying effective drug combinations is challenging due to the vast number of possibilities and limited phenotyping methods.

Purpose of the Study:

To develop a high-throughput method for screening combinatorial drug treatments.
To enable simultaneous analysis of single-cell transcriptomes and drug perturbations.

Main Methods:

Developed combinatorial perturbation sequencing (CP-seq) using microwell-based droplet random pairing.
Utilized oligonucleotide barcoding for drugs and encapsulated cells and drugs in separate droplets.
Employed single-cell RNA sequencing to detect transcriptomes and drug barcodes for treatment demultiplexing.

Main Results:

Demonstrated robust performance of microfluidic droplet operations with up to 83% microwell utilization.
Validated CP-seq through single-drug and combinatorial-drug treatments, confirming its ability to collect and analyze drug-perturbed transcriptomes.
Showcased CP-seq's capability for high-throughput and comprehensive profiling in combinatorial perturbation screening.

Conclusions:

CP-seq is a powerful technology for combinatorial drug screening.
The method leverages droplet microfluidics for massive multiplexing and comprehensive single-cell profiling.
CP-seq facilitates informed drug combination strategies to combat drug resistance and relapse.