Micromachined multichannel systems for the measurement of cellular metabolism

Using living cells as the biological recognition element in a biosensor has two important advantages: cell receptors provide functional rather than structural specificity, and the cells provide second messenger pathways that amplify the receptor/ligand binding events. Cellular responses can be detected by measuring extracellular acidification with a silicon sensor. By using silicon micromachining technology, we can integrate the fluidic pathways and chambers for immobilizing cells with the silicon sensor. We describe a multichannel chip in which each channel is etched into the surface, and has its own flow of tissue-culture medium past the cells. Measurements have been made on adherent cells in which a muscarinic acetylcholine receptor is transfected. Responses to the agonist carbachol are shown.