| AVS 64th International Symposium & Exhibition | |
| MEMS and NEMS Group | Monday Sessions |
| Session MN+BI+NS-MoM |
| Session: | Feature Session: Large Scale Integration of Nanosensors |
| Presenter: | Hao Jia, Case Western Reserve University |
| Authors: | H. Jia, Case Western Reserve University H. Tang, Case Western Reserve University X. Liu, Northwestern University H. Liu, Northwestern University P.X.-L. Feng, Case Western Reserve University |
| Correspondent: | Click to Email |
Non-invasive, microscale positioning of delicate biological cells can foster fundamental research involving probing cellular properties and controlling cellular behaviors and interactions [1-3], which lead to a multitude of applications, such as disease screening, tissue engineering, etc.
Here we demonstrate that microscale manipulation of breast cancer cells can be achieved in a fast and non-invasive manner through exploiting multimode micromechanical systems. We design edge-clamped diaphragm resonators (~300µm in length scale) and piezoelectrically excite their mechanical resonances (within 50–500 kHz) in fluidic environment. The transverse vibrations induce localized, microscale hydrodynamic flow that can aggregate microbeads (3.6µm-diameter) on device surfaces into a variety of one- and two-dimensional (1D and 2D) ‘Chladni figures’ [4] (optical images in Fig.1a & b). This phenomenon allows us to further manipulate single or a group of breast cancer cells (MDA-MB-231, 15µm-diameter), in both 1D and 2D fashions, at a speed of ~4µm/s (fluorescent images in Fig. 1a & b). By simply programming the piezoelectric excitation frequency, we achieve dynamic control of cancer cell spatial distributions, switching between mode patterns.
We further demonstrate that such multimode resonator platform can facilitate cellular-level biological studies, such as evaluating cellular adhesive interactions and its connection with cancer biomarker (e.g., CD44). As shown in Fig.2, by exploiting the ‘Chladni figure’ phenomenon, and carefully selecting 2 resonance modes of a square diaphragm, e.g., Mode (1,1) and Mode (3,3), a controlled number of MDA-MB-231 cells can be quickly manipulated into single cluster and then forced to break as the excitation voltage of Mode (3,3) gradually increases. Cancer cells with CD44 gene knocked out by CRYSPR technology are named as CD44- cells, while those with CD44 gene maintained named as CD44+ (control) cells. The break of CD44- cell cluster after 0.8Vpp in Fig. 2 indicates that they form much weaker adhesive interactions than CD44+ cells do, which indicates that CD44 plays a significant role in the metastatic breast cancer cell clustering.
[1] E.E. Hui, et al., PNAS 104, 2007.
[2] H. Zhang, et al., J. R. Soc. Interface 5, 2008.
[3] X. Ding, et al., PNAS109, 2012.
[4] E.F.F. Chladni, Entdeckungen über die Theory des Klanges,1787.