Central to the development of effective immunotherapeutic interventions is a means to rapidly and accurately detect the illness and effects of intervention. A capability most highly sought after for this purpose is an ultrasensitive, rapid and label-free detection scheme for the sensing of antigens and the protective immune response to those antigens. We collaborate with Electrical engineering and Applied Physics for the development of sensitive and specific sensors that detect clinically relevant T and B cell responses are not only critical for assessment of immunotherapeutic intervention but also for accurate medical diagnostics of infectious diseases including viral, bacterial and parasitic diseases as well as vaccine efficacy.
A mixture of T cells with different specificities (signified by the three different surface receptors—purple, red, and green) is added to the reservoir above an array of nanosensors (gray), integrated into the electronics chip below. The electronics enable a sigle sensor to be activated, shown here in orange. Left: A specific ligand (blue) has just been added which binds and activates only one type of T cell (red). Right: Upon ligand-receptor binding, the T cell is actiated (yellow haze), inducing a change in the current in the nanosensor (orange haze). The array of nanosensors enables different sensing measurements to be performed in parallel and, in turn, ultrasensitive detection of any number of cell types.
Measurement of extracellular acidification upon stimulation lymohocytes with anti-CD3. The CTL response time is ~8 sec. Pre-treatment with Genistein, which inhibits CTL signaling, eliminates anti-CD3 induced cellular metabolic activity.
Stern E, Steenblock E, Reed MA, Fahmy TM, Label-free electronic detection of the antigen-specific immune response. Nanoletters. 2008 Oct;8(10):3310-4.
Stern E, Wagner R, Breaker R, Sigworth F, Fahmy TM, Reed MA. Importance of the Debye Screening Length on Nanowire Field Effect Transistor Sensors. Nanoletters 2007 Nov 14;7(11):3405-3409.
Stern E, Routenberg D, Wyrembak P, Hamilton A, LaVan D, Fahmy TM, Reed MA. Label-Free Immunodetection with CMOS-Compatible Semiconducting Nanowires, Nature, 2007 Feb 1; 445, 519-522.