Theme: Single-Cell Physiochemical Analysis of Metastatic Cancer Cells

Human neoplastic tumors are highly heterogeneous. A subpopulation of tumor cells exists that possesses high rates of proliferation and survival ability, leading to more aggressive phenotypes such as tumor invasion and metastasis. Identifying this highly aggressive subpopulation in solid tumors has been one of the major challenges in understanding tumorigenesis and improving cancer therapy. There is a need for technologies that can distinguish and quantify the highly aggressive subpopulation with respect to other cell populations. Over equal interest are circulating tumor cells (CTCs). Over the past years, CTCs emerged as a prognostic indicator for cancer progression and metastatic assessment as well as a valuable marker for guiding cancer therapies and drug delivery. The presence of a high level of CTCs has been associated with developing of distant tumor metastasis, a worse prognosis, and poor response to chemotherapeutics in cancer patients. While conventional biopsies can provide critical information about solid tumors, those are painfully invasive procedures and provide only circumstantial evidence for metastasis. Technology capable of precise detection and enumeration of CTCs will have a profound and immediate impact on all the clinical aspects of breast cancer diagnostics and therapeutics.

Single-Cell Impedance Spectroscopy
Whole cell impedance spectroscopy (WCIS) to classify breast cancer cells based on cancer progression and head and neck cancer (HNC) cells based on metastatic potentials are being developed. This method does not require labeling of target samples since it measures the intrinsic dielectric properties of samples, requiring only simple instrumentation, and can be easily integrated into microfluidic systems with various sample control and analysis functionalities, hence is an ideal technique for examining cells of various interests. 

Funding Agency: National Institutes of Health (NIH)


- Y. H. Cho, H. Kim, A. B. Frazier, Z. (G). Chen, D. M. Shin, and A. Han, "Whole-Cell Impedance Analysis for Highly and Poorly Metastatic Cancer Cells," J. Microelectromechanical Systems, Vol. 18 (4), pp. 808-817, 2009.
- A. Han, L. Yang, and A. B. Frazier, "Quantification of the Heterogeneity in Breast Cancer Cell Lines using Whole Cell Impedance Spectroscopy," Clinical Cancer Research , Vol. 13, 1, pp. 139-143, 2007.
- K. -H. Han, A. Han, and A. B. Frazier, "Microsystems for Isolation and Electrophysiological Analysis of Breast Cancer Cells in Blood," J. Biosensors and Bioelectronics, Vol. 21, pp. 1907-1914, 2006.



Single-Cell Vibro-Acoustic Platforms
The separation of different particles or cells based on their physical properties (e.g., size, compressibility, and density) has gained significant interest in recent years since no tagging of samples with labels (e.g. fluorescent, magnetic, radioactive) is required. Such label-free separation can significantly reduce the cost and time associated with cumbersome sample preparation steps. However, each of these separation modalities has drawbacks such as low throughput, limited specificity, weak force, complicated microstructures, or need for expensive instrumentations. We are developing acoustic wave based separation technologies that can separate particles and cells based on their vibro-acoustic properties with very simple flow channel structures and instrumentations.

Funding Agency: National Science Foundation (NSF)
- Z. Liu, A. Han, and Y. -J. Kim, "Two-Dimensional Numerical Analysis of Acoustophoresis Phenomena in Microfluidic Channel with Microparticle-Suspended, Viscous, Moving Fluid Medium," Proceedings of the ASME 2012 International mechanical Engineering Congress & Exposition, Houston, 2012.

Support for the NanoBio Systems Lab.