Professor research guide

Stephen Quake

Lee Otterson Professor of Bioengineering and Professor of Applied Physics · Bioengineering and Applied Physics

Stephen Quake develops microfluidic and sequencing approaches to single cells, individual molecules, and nucleic acids in blood. This independent guide distinguishes his lab contributions from collaborations and consortium resources.

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Research primer

Measuring Life: From Single Cells to Liquid Biopsies

6 lessons · ~29 minutes

New measurement tools reveal individual cells, human cell atlases, molecular traces in blood, immune clones, and microbial ecosystems. A video-first introduction to genomics and bioengineering.

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  1. 01Why better measurements change biology
  2. 02Single-cell genomics: why one cell at a time matters
  3. 03Building a map of the human body, one cell at a time
  4. 04Liquid biopsy: reading the body's molecular debris
  5. 05Cell-free RNA: can a blood sample tell us what tissues are doing?
  6. 06From immune systems to microbiomes: what else can sequencing reveal?

Key concepts

Cell-free DNA and liquid biopsy

Interpret fragmented extracellular DNA as a molecular mixture.

Cell-free RNA and tissue-of-origin inference

Explain why cfRNA can carry expression information but source inference needs assumptions.

Genome versus transcriptome and bulk versus single-cell measurement

Distinguish genome, transcriptome and bulk versus single-cell information.

Human cell atlases and reference transcriptomes

Use cell-atlas reference profiles while accounting for sampling and capture bias.

Immune repertoire sequencing and clonal dynamics

Interpret immune clone counts without inferring antigen or complete tissue coverage.

Measurement technology, scale, and microfluidics

Explain how microfluidic scale, isolation and valves change what can be measured.

Metagenomics and quantitative microbial ecology

Separate microbial DNA detection from viability, infection and causal ecology.

Molecular counting in prenatal and transplant monitoring

Relate counting noise, placental DNA and donor DNA to scoped screening and monitoring principles.

Reference atlases, mixture models, and deconvolution

Describe reference-based mixture deconvolution, validation and identifiability limits.

Single-cell RNA sequencing, cell types, and cell states

Interpret RNA matrices, cell types and states without equating clusters with biological identities.

Single-molecule measurement and measurement-driven discovery

Distinguish individual-molecule measurements from averages and sole-invention claims.

Tabula Sapiens and cross-tissue cellular diversity

Explain the consortium atlas and cross-tissue diversity within its donor and tissue scope.

Important papers

Science · 2002

Microfluidic large-scale integration

Thorsen T, Maerkl SJ, Quake SR

Why this matters: HISTORICAL QUAKE-LAB PRIMARY RESULT: integrated chambers and valves automate many measurements.

DOI: 10.1126/science.1076996

Nature · 2022

Early prediction of preeclampsia in pregnancy with cell-free RNA

Moufarrej MN, Vorperian SK, Wong RJ, et al., Stevenson DK, Quake SR

Why this matters: RESEARCH VALIDATION: 404 samples from 199 mothers; an 18-gene panel at 5–16 weeks with independent validation. Possible test basis, not universal clinical readiness.

DOI: 10.1038/s41586-022-04410-z

Nat Biotechnol · 2022

Cell types of origin of the cell-free transcriptome

Vorperian SK, Moufarrej MN, Tabula Sapiens Consortium, Quake SR

Why this matters: CONSORTIUM / COLLABORATIVE PRIMARY RESULT: Tabula Sapiens reference-based nu-SVR validated on bulk tissues. Similar and missing signatures limit identifiability.

DOI: 10.1038/s41587-021-01188-9