Usually when you think of optics and light, you think of looking at something. In this lab we indeed use optical tools to “look at” the inner working of living things, but we also do more with optics. One aim of our research is to develop techniques that allow us to perturb and manipulate the biological systems we are watching, and it turns out that light is an ideal tool for this task as well. We use very short laser pulses (measured in millionths of billionths of a second in duration) to make cuts with a width of less than one-tenth the diameter of a single cell. These cuts can even be completely inside a tissue (i.e. we can cut inside without distrubing the surface). We use this ultra-precise laser scalpel to locally damage the sample we are studying, and then we observe the reaction. For example, we have found that by making a small cut to a single blood vessel in the brain of a rodent we can cause that blood vessel to clot (just like your hand clots after a small cut). We use these single-vessel blood clots to help understand and develop treatments for stroke.
Clinical evidence shows that ischemic and hemorrhagic microvascular lesions in the brain play an important role in elderly dementia, but few effective treatment or preventative strategies exist. This deficit is due, in part, to a lack of good animal models of these small-scale strokes that would allow the progression of disease to be studied and would provide a platform for the evaluation of therapeutics.
One way to elucidate the function of part of a system is to disrupt and break that part and observe the effect. Using molecular biology tools, this method has led to a better understanding of the genetic origins of many diseases through studies of knock-out and knock-in transgenic animals, for example. While such genetic manipulation technologies are very advanced, techniques for physical disruption, especially of very fine-scale or difficult to access structures, remain crude. Development of technologies that allow specifically targeted structures to be disrupted with sub-micrometer spatial precision, without significant collateral effects, and in native, in vivo environments would open the door to a variety of studies that could match the impact transgenic experiments have had.
We use the nonlinear interactions between femtosecond laser pulses and transparent materials as a means to produce micrometer-scale alteractions of the properties of the material. We can ablate material, producing a hole, or produce more subtle refractive index changes. With these tools, we can directly write three-dimensional patterns of optical waveguides and microfluidic channels into a transparent material, for example. In addition, a focus of our research is the development of a comprehensive understanding of the nonlinear interaction mechanisms between femtosecond pulses and transparent matter.