Single-cell omics with Live-seq


The novel method that keeps your cells alive during biopsy from single cells

Repeatedly take a biopsy from the same cell

Since the extraction preserves cell viability, extract several times from the same cell within the same run or periodically over time.

Maintain physiological context

Take a biopsy from a cell without altering gene expression, cell phenotype, or cell-cell interactions. You’ll get results you can trust.

Obtain representative biopsies

Gene expression profiles obtained from single-cell biopsies are suitable representations of lysed cell transcriptomes. (Chen et al., 2021)

Analyze temporal gene expression

Extrapolate the future and correlate the past by sequentially profiling the transcriptome of the same individual cell.   

It's time to level up your omics studies

About Live-seq: Temporal single-cell omics made possible

Cellular heterogeneity is a formidable opponent when it comes to understanding human biology, mapping disease progression, and advancing therapeutic developments. Single-cell omics addresses cellular heterogeneity head on by isolating and analyzing molecular components from individual cells. While many of the existing technologies are capable of high-throughput single-cell processing, they rely on cell lysis—making it impossible to directly link individual cells to downstream molecular and phenotypic states.


Live-seq brings a new paradigm to single-cell omics by enabling researchers to take transcriptome snapshots of a cell without killing it. And it is so easy, new lab members can perform it.


The Live-seq method pairs the FluidFM OMNIUM system with a highly sensitive low-input RNA-seq protocol, which stems from a collaboration between ETH Zurich and EPFL. The FluidFM OMNIUM allows you to extract sub-picoliter volumes from subcellular compartments of a living single cell and then isolate the extract for further analysis. By avoiding destructive methods, such as cell lysis, you can perform further downstream molecular and phenotypic analysis and even transcriptome profiling over time on the very same cell, bringing trajectory instead of end-point analysis to your transcriptomics, metabolomics, proteomics, or any other omics studies.

It's time to level up your omics studies

  • Record a cell transcriptome prior to phenotyping

  • Record transcriptional events over time to reveal how molecular components influence cell behavior

  • Directly link an individual cell’s history and trajectory to unravel past cell states and understand lineage decisions 

  • Take a biopsy from cells of a heterogeneous disease before and after exposure to a specific therapeutic to identify molecular signatures for early drug development


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Benefits of the FluidFM OMNIUM in single-cell omics

Not only does our system save cell lives, it saves you time and precious cellular material.

 
 

FluidFM in action: Non-destructive extraction of cellular content

Highly automated 

Highly automated application-specific workflows and probe handling.

Easy-to-use, point & click interfaces

Intuitive software with easy cell selection – point-and-click to target a specific cell.

Optimized probes

Hollow, force-sensitive probes particularly designed for specific applications.

Advance your omics research with FluidFM

Live-seq: How it works


Powered by FluidFM technology + a highly sensitive low-input RNA-seq protocol

The method

For the Live-seq method, the FluidFM OMNIUM system collects sub-cellular amounts of RNA without disrupting cellular viability or physiology. Then, a highly sensitive low-input RNA-seq protocol by Chen et al. (2021) provides a downstream analysis of the transcriptome. (Chen et al., 2021 & Guillaume-Gentil et al., 2016)

The system

We’ve designed the FluidFM OMNIUM as a stand-alone, easy-to-use, automated system. After you set your parameters and hit start, the system does the rest. It also automatically washes and cleans the probes, so even if you use the same probe on different cells, there is no cross contamination.
More on the FluidFM OMNIUM

The probes

Our systems work with our patented, hollow, force-controlled FluidFM Probes that exist in a variety of tip shapes, aperture sizes and mechanical specifications. The FluidFM Nanosyringe is specifically designed for gentle injection into and extraction from single cells. It is the tiniest syringe, so small that it can be inserted into a cell without causing harm.
More on FluidFM Probes & technology

Find out more about the FluidFM OMNIUM

Explore FluidFM publications

Genome-wide molecular recording using Live-seq

Chen et al. show the establishment of Live-seq, an approach for single-cell transcriptome profiling that preserves cell viability during RNA extraction using FluidFM. By using a model involving exposure of macrophages with lipopolysaccharide (LPS), they were able to apply a genome-wide ranking of genes based on their ability to impact macrophage LPS response heterogeneity.  Furthermore, they show that Live-seq can be used to sequentially profile the transcriptomes of individual macrophages before and after stimulation with LPS. This enables the direct mapping of a cell’s trajectory and transforms scRNA-seq from an end-point to a temporal analysis approach.


W. Chen, O. Guillaume-Gentil, P. Yde Rainer, C. G. Gäbelein, W. Saelens, V. Gardeaux, A. Klaeger, R. Dainese, M. Zachara, T. Zambelli, J. A. Vorholt & B. Deplancke. Live-seq enables temporal transcriptomic recording of single cells. (Aug 2022) Nature, doi:10.1038/s41586-022-05046-9



Single-Cell Mass Spectrometry

In this publication Guillaume-Gentil et al. show non-destructive and quantitative withdrawal of intracellular fluid with sub-picoliter resolution using FluidFM, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. By this method they detected and identified several metabolites from the cytoplasm of individual HeLa cells. Validated by 13C-Glucose feeding experiments, this showed that metabolite sampling combined with mass spectrometry analysis was possible while preserving the physiological context and the viability of the analyzed cell. Thus, enabling complementary analysis of the cell. 


O. Guillaume-Gentil, T. Rey, P. Kiefer, A.J. Ibáñez, R. Steinhoff, R. Brönnimann, L. Dorwling-Carter, T. Zambelli, R. Zenobi & J.A. Vorholt. Single-Cell Mass Spectrometry of Metabolites Extracted from Live Cells by Fluidic Force Microscopy. (May 2017) Anal Chem., 89(9), 5017-5023. doi:10.1021/acs.analchem.7b00367



Tunable Single-Cell Extraction for Molecular Analyses

Guillaume-Gentil et al. demonstrate the use of FluidFM for quantitative sampling of cytoplasmic and nucleoplasmic fractions from single cells at a sub-picoliter resolution followed by a comprehensive analysis of the soluble molecules withdrawn from the cytoplasm or the nucleus and dispensed adaptable to a broad range of analytical methods, including the detection of enzyme activities and transcript abundances.


O. Guillaume-Gentil, R.V. Grindberg, R. Kooger, L. Dorwling-Carter, V. Martinez, D. Ossola, M. Pilhofer, T. Zambelli & J.A. Vorholt. Tunable Single-Cell Extraction for Molecular Analyses. (Jul 2016) Cell, 166(2), 506-516. doi: 10.1016/j.cell.2016.06.025.

80+ publications with FluidFM