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영어

Microsystems have the potential to impact biology by providing new ways to manipulate cells and the microenvironment around them. Simply physically manipulating cells or their environment—using microfluidics, electric fields, or optical forces—provides new ways to separate cells and organize cell-cell interactions. One example illustrating the power of microscale manipulation of cells is to sort cells based on their intrinsic electrical properties. Electrical properties have previously been correlated with important biological phenotypes (apoptosis, cancer, etc.), but a sensitive and specific method approach has been lacking. We have developed a method called iso-dielectric separation that uses electric fields to drive cells to the point in a conductivity gradient where they become electrically transparent, resulting in a continuous separation method specific to electrical properties. With this method, we have screened the entire genome of an organism to understand the biological basis of electrical properties, finding that the relationship between genetics and intrinsic properties has both intuitive and non-intuitive features. Microfluidics can also be used to manipulate the environment around cells. For example, we have developed arrays of microfluidic perfusion culture chambers that use fluid flow to create a convection-dominated transport environment, allowing control over local cell-cell diffusible signaling. This in turn provides a more controlled soluble microenvironment in which to study diffusible signaling in cell systems. In particular, we have examined the impact of diffusible signaling on self-renewal and neural specification of embryonic stem cells. Using these microsystems, we have identified the existence of previously unknown autocrine loops involved in fate specification, and have delineated the effects of shear itself on self-renewal. Together, these new microscale tools provide ways to exploit cells’ potential for both basic science and applied biotechnology.