| AVS 63rd International Symposium & Exhibition | |
| MEMS and NEMS | Thursday Sessions |
| Session MN+BI-ThM |
| Session: | ‘Fantastic Voyage’ – the New Micro/Nano/Bio Systems Frontiers |
| Presenter: | Hao Jia, Case Western Reserve University |
| Authors: | H. Jia, Case Western Reserve University H. Tang, Case Western Reserve University P.X.-L. Feng, Case Western Reserve University |
| Correspondent: | Click to Email |
Manipulating and patterning biological cells on surfaces has gained great interest due to its fundamental importance for cell-level biophysical studies, and implications for potential biomedical applications.1 In this work, we report the first experimental demonstration of non-invasive, fast, dynamic patterning of clusters of cancer cells with micrometer-scale spatial precision, by using multimode silicon nitride (Si3N4) membrane resonators that feature very large aspect ratios (~600nm-thick, and hundreds of microns in lateral dimensions), in rectangular and square shapes. The fabricated Si3N4 membranes exhibit robust multiple flexural resonances (within 50–500 kHz) in liquid solutions. We observe that the breast cancer cells (MDA-MB-231) can be dynamically manipulated into diverse Chladni patterns2 within a few seconds, via the multimode resonances of the membrane. Multiple spatially signatory cell patterns are observed for rectangles (~300×120µm2) and squares (~350×350µm2), respectively. We further demonstrate that cell patterns can be dynamically switched. We model and explain the cell patterns by oscillating boundary induced acoustic steaming flows of the fluid.
As an important cell line for breast cancer metastasis studies, MDA-MB-231 cells are selected in this work and genetically-engineered to express green florescent protein (GFP), a biomarker for gene expression and cell identification. Dilution in EDTA solution allows suspended individual cells with reduced surface viscosity. Cancer cells are locally delivered to the device area using micropipettes, and the cell distributions are imaged in real time by a high-speed fluorescent microscope. We observe that cancer cells are allocated into ‘1D’ array of clusters on the rectangular membrane under excitation frequencies corresponding to its 1st, 2nd and 3rd modes (in Fig. 1), while they cluster into multiple ‘2D’ patterns when the multiple modes of square membrane are excited individually (in Fig. 2). Furthermore, the cell patterns can be readily changed when switching between resonance frequencies.
The demonstrated Si3N4 membrane platform provides new capabilities for manipulating breast cancer cells, which could further lead to studies involving cancer cell signaling and interaction with neighboring cells, probing and controlling cancer cell metastatic behaviors using multimode mechanical resonators.
[1] B. Guillotin, et al., Trends in Biotechnology4, 2011.
[2] E.F.F. Chladni, Entdeckungen über die Theory des Klanges, 1787.