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Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):E3661-8. doi: 10.1073/pnas.1509250112. Epub 2015 Jun 29.

Magnetic levitation of single cells.

Author information

1
Department of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304; Stanford Genome Technology Center, Stanford University, Stanford, CA 94304;
2
Canary Center at Stanford for Cancer Early Detection, Radiology Department, School of Medicine, Stanford University, Stanford, CA 94304;
3
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; jeanne.thompson@stanford.edu larsms@stanford.edu utkan@stanford.edu.
4
Department of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304; Stanford Genome Technology Center, Stanford University, Stanford, CA 94304; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94304 jeanne.thompson@stanford.edu larsms@stanford.edu utkan@stanford.edu.
5
Stanford Genome Technology Center, Stanford University, Stanford, CA 94304; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94304 jeanne.thompson@stanford.edu larsms@stanford.edu utkan@stanford.edu.
6
Canary Center at Stanford for Cancer Early Detection, Radiology Department, School of Medicine, Stanford University, Stanford, CA 94304; jeanne.thompson@stanford.edu larsms@stanford.edu utkan@stanford.edu.

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.

KEYWORDS:

cancer; cell densitometry; magnetic levitation; real-time monitoring; single cells

PMID:
26124131
PMCID:
PMC4507238
DOI:
10.1073/pnas.1509250112
[Indexed for MEDLINE]
Free PMC Article

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