Overview
The Manalis Lab develops precision measurement technologies to interrogate the physical and functional properties of single cells, with the goal of advancing our understanding and treatment of cancer and other diseases. Our interdisciplinary approach integrates engineering, microfluidics, cell biology, and translational science to create innovative tools that address key clinical challenges—particularly those related to disease heterogeneity, therapeutic resistance, and residual disease. By enabling more precise and dynamic measurements of individual cells, our work contributes to the broader mission of personalized medicine.
A core focus of our lab is the development of label-free, single-cell assays that combine morphological and biophysical profiling to reveal phenotypic and functional diversity across both cancer and immune cell populations. These approaches provide integrated readouts of cell state—such as activation, exhaustion, or resistance—that not only avoids reliance on molecular labels but, in some contexts, offers greater accuracy than conventional molecular markers. In cancer, this has the potential to more reliably identify residual disease and help guide individualized treatment selection. In the immune system, our technologies are being developed to customize CAR-T cell therapies and predict patient responses to immune checkpoint inhibitors, offering new strategies for tailoring immunotherapy based on functional immune cell phenotypes.
Examples
Personalized medicine
Integrating Single-Cell Biophysical and Transcriptomic Features to Resolve Functional Heterogeneity in Mantle Cell Lymphoma, in review. bioRxiv
Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer spheroid models, Cell Reports (2021). Download PDF and Suppl. Info. See also MIT News.
Targeting minimal residual disease: a path to cure?, Nature Reviews Cancer (2018). Download PDF
Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation, Nature Communications (2017). Download PDF and Suppl. Info. See also MIT News.
Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate, Nature Biotechnology (2016). Download PDF and Suppl. Info. See also MIT News.
Device engineering
Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples, Nature Biomedical Engineering (2025). Download PDF and Suppl. Info. See also MIT News.
Noninvasive monitoring of single-cell mechanics by acoustic scattering, Nature Methods (2019). Download PDF and Suppl. Info. See also MIT News.
High-throughput single-cell growth measurements via serial microfluidic mass sensor arrays, Nature Biotechnology (2016). Download PDF and Suppl. Info. See also MIT News.
Weighing nanoparticles in solution at the attogram scale, PNAS (2014). Download PDF and Suppl. Info. See also MIT News.
Measuring single-cell density, PNAS (2011). Download PDF. Animation. See also MIT News.
Weighing of Biomolecules, Single Cells, and Single Nanoparticles in Fluid, Nature, 446 1066 (2007). Download PDF. See also News & Views.
Cell growth and metabolism
Single-cell monitoring of dry mass and dry density reveals exocytosis of cellular dry contents in mitosis, eLife (2022). Download PDF and Suppl. Info. See also MIT News.
Mammalian cell growth dynamics in mitosis, eLife (2019). Download PDF.
Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes, Journal of Cell Biology (2016). Download PDF and Suppl. Info. See also JCB In Focus.
Direct observation of mammalian cell growth and size regulation, Nature Methods (2012). Download PDF. See also MIT News. Highlight in Nature Methods.
Cooperative nutrient accumulation sustains growth of mammalian cells, Scientific Reports (2015). Download PDF and Suppl. Info.
Cellular biophysics
Linking single-cell measurements of mass, growth rate and gene expression, Genome Biology (2018). Download PDF and Suppl. Info. See also MIT News.
Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes, Journal of Cell Biology (2016). Download PDF and Suppl. Info. See also JCB In Focus.
Intracellular water exchange for measuring the dry mass, water mass and changes in chemical composition of living cells. PLoS ONE (2013). Download PDF. See also Suppl. Info.
Characterizing deformability and surface friction of cancer cells, PNAS (2013). Download PDF. See also MIT News.
Other areas
Biomanufacturing
The state of technological advancement to address challenges in the manufacture of rAAV gene therapies, Biotechnology Advances (2024). Download PDF
Weighing the DNA content of Adeno-Associated Virus vectors with zeptogram precision using nanomechanical resonators, Nano Letters (2022). Download PDF and Suppl. Info. See also Cell and Gene summary.
Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies, Mol Ther Methods Clin Dev (2021). Download PDF
Enviromental microbiology
Direct quantification of sinking velocities across unicellular algae, Science Advances (2024). Download PDF
Single-cell mass distributions reveal simple rules for achieving steady-state growth, mBio (2023). Download PDF
Direct single-cell biomass estimates for marine bacteria via Archimedes’ principle, International Society for Microbial Ecology Journal (2017). Download PDF.