Investigating contactless high frequency ultrasound microbeam stimulation for determination of invasion potential of breast cancer cells

Jae Youn Hwang, Nan Sook Lee, Changyang Lee, Kwok Ho Lam, Hyung Ham Kim, Jonghye Woo, Ming Yi Lin, Kassandra Kisler, Hojong Choi, Qifa Zhou, Robert H. Chow, K. Kirk Shung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

27 Citations (Scopus)


In this article, we investigate the application of contactless high frequency ultrasound microbeam stimulation (HFUMS) for determining the invasion potential of breast cancer cells. In breast cancer patients, the finding of tumor metastasis significantly worsens the clinical prognosis. Thus, early determination of the potential of a tumor for invasion and metastasis would significantly impact decisions about aggressiveness of cancer treatment. Recent work suggests that invasive breast cancer cells (MDA-MB-231), but not weakly invasive breast cancer cells (MCF-7, SKBR3, and BT-474), display a number of neuronal characteristics, including expression of voltage-gated sodium channels. Since sodium channels are often co-expressed with calcium channels, this prompted us to test whether single-cell stimulation by a highly focused ultrasound microbeam would trigger Ca2+elevation, especially in highly invasive breast cancer cells. To calibrate the diameter of the microbeam ultrasound produced by a 200-MHz single element LiNbO3transducer, we focused the beam on a wire target and performed a pulse-echo test. The width of the beam was ~17μm, appropriate for single cell stimulation. Membrane-permeant fluorescent Ca2+indicators were utilized to monitor Ca2+changes in the cells due to HFUMS. The cell response index (CRI), which is a composite parameter reflecting both Ca2+elevation and the fraction of responding cells elicited by HFUMS, was much greater in highly invasive breast cancer cells than in the weakly invasive breast cancer cells. The CRI of MDA-MB-231 cells depended on peak-to-peak amplitude of the voltage driving the transducer. These results suggest that HFUMS may serve as a novel tool to determine the invasion potential of breast cancer cells, and with further refinement may offer a rapid test for invasiveness of tumor biopsies in situ.
Original languageEnglish
Pages (from-to)2697-2705
Number of pages9
JournalBiotechnology and Bioengineering
Issue number10
Publication statusPublished - 1 Jan 2013
Externally publishedYes


  • Calcium fluorescence imaging
  • Cell stimulation
  • High frequency ultrasound microbeam
  • Invasiveness, breast cancer cells
  • Live-cell imaging
  • Mechanotransduction

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this