Instrumentation challenges for systems biology

Burgeoning genomic and proteomic data are motivating the development of numerical models for systems biology. However, specification of the almost innumerable dynamic model parameters will require new measurement techniques. The problem is that cellular metabolic reactions and the early steps of intracellular signaling can occur in ms to s, but the 100 to 100 ks temporal resolution of measurements on milliliter culture dishes and well plates is often limited by diffusion times set by the experimental chamber volume. Hence the instruments themselves must be of cellular dimension to achieve response times commensurate with key intracellular biochemical events, as is done with microelectrode recording of ion-channel conductance fluctuations and fluorescence detection of protein binding. The engineering challenge is to develop BioMEMS and molecular-scale sensors and actuators to study the breadth of mechanisms involved in intracellular signaling, metabolism, and cell-cell communication.