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A few nascent methods for measuring mechanical properties of the biological cell

Sumali, Hartono S.; Corwin, Alex D.; Thayer, Gayle E.; De Boer, Maarten P.; Koch, Steven J.

This report summarizes a survey of several new methods for obtaining mechanical and rheological properties of single biological cells, in particular: (1) The use of laser Doppler vibrometry (LDV) to measure the natural vibrations of certain cells. (2) The development of a novel micro-electro-mechanical system (MEMS) for obtaining high-resolution force-displacement curves. (3) The use of the atomic force microscope (AFM) for cell imaging. (4) The adaptation of a novel squeezing-flow technique to micro-scale measurement. The LDV technique was used to investigate the recent finding reported by others that the membranes of certain biological cells vibrate naturally, and that the vibration can be detected clearly with recent instrumentation. The LDV has been reported to detect motions of certain biological cells indirectly through the motion of a probe. In this project, trials on Saccharomyces cerevisiae tested and rejected the hypothesis that the LDV could measure vibrations of the cell membranes directly. The MEMS investigated in the second technique is a polysilicon surface-micromachined force sensor that is able to measure forces to a few pN in both air and water. The simple device consists of compliant springs with force constants as low as 0.3 milliN/m and Moire patterns for nanometer-scale optical displacement measurement. Fields from an electromagnet created forces on magnetic micro beads glued to the force sensors. These forces were measured and agreed well with finite element prediction. It was demonstrated that the force sensor was fully functional when immersed in aqueous buffer. These results show the force sensors can be useful for calibrating magnetic forces on magnetic beads and also for direct measurement of biophysical forces on-chip. The use of atomic force microscopy (AFM) for profiling the geometry of red blood cells was the third technique investigated here. An important finding was that the method commonly used for attaching the cells to a substrate actually modified the mechanical properties of the cell membrane. Thus, the use of the method for measuring the mechanical properties of the cell may not be completely appropriate without significant modifications. The latest of the studies discussed in this report is intended to overcome the drawback of the AFM as a means of measuring mechanical and rheological properties. The squeezing-flow AFM technique utilizes two parallel plates, one stationary and the other attached to an AFM probe. Instead of using static force-displacement curves, the technique takes advantage of frequency response functions from force to velocity. The technique appears to be quite promising for obtaining dynamic properties. More research is required to develop this technique.