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Magnetic levitation of single cells
Contributed by Ronald W. Davis, May 18, 2015 (sent for review April 17, 2015)

Significance
Cells consist of micro- and nanoscale components and materials that contribute to their fundamental magnetic and density signatures. Previous studies have claimed that magnetic levitation can only be used to measure density signatures of nonliving materials. Here, we demonstrate that both eukaryotic and prokaryotic cells can be levitated and that each cell has a unique levitation profile. Furthermore, our levitation platform uniquely enables ultrasensitive density measurements, imaging, and profiling of cells in real-time at single-cell resolution. This method has broad applications, such as the label-free identification and monitoring of heterogeneous biological changes under various physiological conditions, including drug screening in personalized medicine.
Abstract
Several cellular events cause permanent or transient changes in inherent magnetic and density properties of cells. Characterizing these changes in cell populations is crucial to understand cellular heterogeneity in cancer, immune response, infectious diseases, drug resistance, and evolution. Although magnetic levitation has previously been used for macroscale objects, its use in life sciences has been hindered by the inability to levitate microscale objects and by the toxicity of metal salts previously applied for levitation. Here, we use magnetic levitation principles for biological characterization and monitoring of cells and cellular events. We demonstrate that each cell type (i.e., cancer, blood, bacteria, and yeast) has a characteristic levitation profile, which we distinguish at an unprecedented resolution of 1 × 10−4 g⋅mL−1. We have identified unique differences in levitation and density blueprints between breast, esophageal, colorectal, and nonsmall cell lung cancer cell lines, as well as heterogeneity within these seemingly homogenous cell populations. Furthermore, we demonstrate that changes in cellular density and levitation profiles can be monitored in real time at single-cell resolution, allowing quantification of heterogeneous temporal responses of each cell to environmental stressors. These data establish density as a powerful biomarker for investigating living systems and their responses. Thereby, our method enables rapid, density-based imaging and profiling of single cells with intriguing applications, such as label-free identification and monitoring of heterogeneous biological changes under various physiological conditions, including antibiotic or cancer treatment in personalized medicine.
Footnotes
↵1N.G.D. and H.C.T. contributed equally to this work and are listed alphabetically.
- ↵2To whom correspondence may be addressed. Email: jeanne.thompson{at}stanford.edu, larsms{at}stanford.edu, or utkan{at}stanford.edu.
Author contributions: N.G.D., H.C.T., I.G., R.W.D., L.M.S., and U.D. designed research; N.G.D., H.C.T., S.G., K.S., A.A.Y., and G.C. performed research; N.G.D., H.C.T., L.M.S., and U.D. contributed new reagents/analytic tools; N.G.D., H.C.T., R.W.D., L.M.S., and U.D. analyzed data; and N.G.D., H.C.T., R.W.D., L.M.S., and U.D. wrote the paper.
Conflict of interest statement: U.D. is a founder of and has an equity interest in DxNow Inc., a company that is developing microfluidic and imaging technologies for point-of-care diagnostic solutions, and Koek Biotech, a company that is developing microfluidic IVF technologies for clinical solutions.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1509250112/-/DCSupplemental.
Freely available online through the PNAS open access option.