Chemotaxis

The process of chemotaxis, where cells exhibit directed movement in response to external concentration gradients, is important in inflammation, wound-healing, and cancer metastasis. Cells migrating through tissues experience multiple, overlapping gradients. However, traditional chemotaxis assays are unable to generate stable gradients and cannot produce multiple gradients. In addition, many assays do not allow real-time observation of the cells. Using microfluidic channels, we can produce stable concentration gradients of relevant substances and expose cells to these gradients in a controlled microenvironment. We can generate single and multiple gradients, both spatially and temporally, and we can observe locomotion of individual cells in real time.

The chemotaxis projects in the lab focus on two cell types: neutrophils, which are white blood cells; and metastatic breast cancer cells. Inside the body, chemotaxis is the mechanism by which neutrophils find their way to the sites of infection and injury during the process of inflammation. For breast cancer cells, chemotaxis is involved in metastasis, as cells break away from the primary tumor and invade other tissues. By studying the migration of these cell types in precisely controlled gradients, we can gain detailed insight into these processes that may lead to better treatment and diagnosis.
Neuroscience
The focus of our research is to develop, test and implement a novel microfabricated, multi-compartment neuronal culture chamber for neuroscience research. A single neuron can extend through various microenvironments within the brain. For example, Alzheimer's Disease and aging brains may have microenvironments, such as areas of oxidative damage, beta-amyloid aggregation, and areas of excitotoxicity damage. In order to simulate such conditions in vitro, we created a novel multi-compartment chamber using microfabrication and soft lithography techniques.
This chamber allows active control and fluidic isolation of neuronal microenvironments, and may result in new avenues of research for neurodegenerative diseases. It is believed that microfabricated neuronal chambers of this type have yet to be developed. Advantages of this chamber over standard culturing methods include increased control over neuronal microenvironments and less reagent usage. By using microfabrication technology, culturing chambers can be created reproducibly, precisely, and rapidly. The chamber is fabricated from an optically transparent polymer, which allows live cell imaging. Microfluidics are used to fluidically isolate domains within the culture area with the ability to deliver positive or negative stimuli to the soma or neurites. Additionally, this chamber can be coupled with substrate patterning to direct the sites of neuronal attachment, orientation, and length of neurite outgrowth.