Microfabricated Biosensors for Monitoring Cell Metabolism

Physiological or pathophysiological state of cells and organs is reflected in their metabolism.   Glucose consumption of cancer cells differs strikingly from normal tissue in that glycolysis is prominent in tumors under both anaerobic and aerobic conditions.  Therapeutic strategies for cancer treatment are increasingly being designed to target this metabolic deviation, making glucose and lactate potential correlates of drug efficacy.  Another important biological system tightly connected to energy metabolism is the liver.  This organ maintains a program of glucose release and storage in response to hormonal stimulation establishing glucose homeostasis.  Imbalances in this program are closely implicated in Type 1 and Type 2 diabetes, as well as, obesity.  Given the importance of monitoring cellular metabolism, measurements of glucose, lactate and other metabolites are performed widely in basic research and clinical settings.  However, these traditional metabolite detection methods require large cell numbers, reveal little about metabolism dynamics and allow to expose cells to only one stimulus at a time.  Such approaches are not suited for monitoring scarce cells (primary human cells, cancer cells retrieved from biopsies) or screening the effects of drug candidates and toxicants on cells.  We are developing novel lab-on-chip biosensor platform for in vitro monitoring of cell metabolism.  This platform is designed to use a small number of cells as well as intimately integrate cells with biosensors in order to detect extracellular metabolite fluxes.  In addition, a microfluidic delivery is incorporated with cells/biosensors in order to multiplex delivery of stimulants and control soluble microenvironment (e.g. create concentration gradients) in the vicinity of the cells.  The devices under development in our laboratory are envisioned as "screening" tools for exposing liver cells to potential toxicants or challenging cancer cells with anti-cancer drug candidates. 
(Researchers involved on this project: Jun Yan, David Dyer, He Zhu)

Microbiosensors integrated with cells.  (A) Macrophages reside in the immediate vicinity of an optical biosensor for hydrogen peroxide detection.  (B) SEM micrograph showing that cells are located next to the sensing element but do not attach to it.  This is a demonstration of our efforts to effectively integrate and juxtapose small groups of cells with microbiosensors.  (C) An array of sensing hydrogel microstructures responding to glucose.  In the future this array will be integrated with cells and will be able to detect multiple metabolites simultaneously.