Scott Manalis, PhD

Email: 

Phone: 

(617) 253-5039
Professor of Biological and Mechanical Engineering

Research-at-a-glance: 

Suspended Microchannel Resonators
Monitoring Cell Growth
Single cell biophysical properties
Biomolecular detection

Affiliations: 

Member, Koch Institute for Integrative Cancer Research at MIT

Biography: 

Scott Manalis has been a faculty member at MIT since 1999. He received the B.S. degree in physics from the University of California, Santa Barbara in 1994, and the PhD degree in applied physics from Stanford University, Palo Alto, CA in 1998.

Image of Suspended Microchannel Resonator.
The Suspended Microchannel Resonator can be used to analyze the weights of single cells, nanoparticles and biomolecules

Research: 

We develop microfluidic technologies to measure biophysical properties of single cells (e.g. mass, growth, deformability) and we apply these technologies to problems in cancer, immunology, and microbial research.  Our research projects generally fall within the following areas:

Functional assays for precision medicine in cancer
Despite tremendous advances in our understanding of cancer pathogenesis, the treatment of individual patients with either conventional chemotherapy or targeted agents remains highly empiric.  Better information about which treatment to offer an individual patient could improve efficacy while sparing patients from the toxicity of therapies that offer no benefit. To address this need, we are developing new technology platforms for predicting therapeutic response in which biophysical properties of individual tumor cells are measured in response to ex vivo treatment of combination therapies.  Through a U54 Center Grant from the NCI Cancer Systems Biology Consortium, we are utilizing these platforms within clinical studies in a broad range of tumor types, including leukemias, glioblastoma, colon and pancreatic cancers.

Linking biophysical to genomic properties in single cells 
We are pursuing several directions where high precision measurement of single cell biophysical properties reveals interesting subpopulations.   Examples include activated immune cells with divergent growth kinetics, bacteria responses to antibiotics or antimicrobial peptides and tumor cell response to targeted therapies.  In collaboration with the Shalek Lab (MIT Chemistry), we are linking biophysical properties to gene expression (sc-RNA-Seq) at the single-cell level and at scale in order to understand the mechanisms that govern growth heterogeneity in these examples.

Real-time monitoring of circulating tumor cells in genetically engineered mouse models 
Despite the central importance of circulating tumor cells (CTCs), understanding of their role in metastasis has been limited by the extreme difficulty of characterizing CTC populations over time and linking them to metastases that occur during natural tumor progression. Genetically engineered mouse models (GEMMs) have emerged as an attractive model for recapitulating the natural multistage evolution of cancers as they now allow for inducible, tissue-specific expression of oncogenes as well as conditional, tissue-specific deletion of tumor suppressors. In collaboration with the Jacks lab (MIT Biology), we are using GEMMs together with microfluidic technology to understand how progression to metastasis correlates with, and could be explained by, the circulatory dynamics and physical properties of CTCs. Our approach will make possible a series of experiments that can answer fundamental questions about the relationship between CTC characteristics and metastasis and will ultimately potentiate hypothesis-driven tumor biology studies and large-scale preclinical exploration of therapeutic strategies that are not feasible in patients. 

Research Areas: 

Honors & Awards: 

Andrew and Erna Viterbi Professorship in Biological Engineering, 2014
Elected to College of Fellows, American Institute for Medical and Biological Engineering, 2013
Baker Award for Excellence in Undergraduate Teaching, 2009
MIT Technology Review TR100, 2002
Presidential Early Career Award for Scientists and Engineers, AFOSR, 2002

Selected Publications:

Olcum, Selim, Nathan Cermak, Steven C. Wasserman, Kathleen S. Christine, Hiroshi Atsumi, Kris R. Payer, Wenjiang Shen, Jungchul Lee, Angela M. Belcher, Sangeeta N. Bhatia et al. "Weighing nanoparticles in solution at the attogram scale." Proc Natl Acad Sci U S A 111, no. 4 (2014): 1310-5.
Byun, Sangwon, Sungmin Son, Dario Amodei, Nathan Cermak, Josephine Shaw, Joon Ho Kang, Vivian C. Hecht, Monte M. Winslow, Tyler Jacks, Parag Mallick et al. "Characterizing deformability and surface friction of cancer cells." Proc Natl Acad Sci U S A 110, no. 19 (2013): 7580-5.
Son, Sungmin, Amit Tzur, Yaochung Weng, Paul Jorgensen, Jisoo Kim, Marc W. Kirschner, and Scott R. Manalis. "Direct observation of mammalian cell growth and size regulation." Nat Methods 9, no. 9 (2012): 910-2.
Burg, Thomas P., John E. Sader, and Scott R. Manalis. "Nonmonotonic energy dissipation in microfluidic resonators." Phys Rev Lett 102, no. 22 (2009): 228103.
Burg, Thomas P., Michel Godin, Scott M. Knudsen, Wenjiang Shen, Greg Carlson, John S. Foster, Ken Babcock, and Scott R. Manalis. "Weighing of biomolecules, single cells and single nanoparticles in fluid." Nature 446, no. 7139 (2007): 1066-9.