Sponsors: NSF, Stanford University
Students: Dr. Shilpi Roy

Thermal transport and temperature distributions have a profound impact on the health, growth, modification, and diagnostics of cells and biological molecules including DNA. The vast majority of research in biochemistry and biomedicine has focused on these phenomena under carefully controlled – but spatially and temporally uniform – temperature conditions. However, there is a rich set of problems in which micro/nanoscale temperature changes can leveraged, e.g., for the study of basic reactions or for the development of new surgical techniques. A key related challenge is the design and analysis of bioprocessing structures, including those based on MEMS, which must maintain or detect temperature distributions at short length and timescales.

Early work on this topic measured the electrical and thermal transport properties of metal-coated DNA strands. More recent work is developing MEMS structures to detect biochemical reactions by means of the associated heat release (and temperature rise) in a small liquid volume. The main focus of this work is on energy transformation in organisms, structures, and cells, as well as the chemical processes underlying these transductions. Of particular interest is the DNA melting reaction, such as the thermally-induced transition of double-stranded DNA to single-stranded DNA. Prior research has focused on the impact of temperature gradients, generated using a suspended MEMS heater/thermometer structure, on the growth and health of retinal ganglion cells. Our work has also explored the use of temperature gradients to separate and detect biomolecules including DNA.

(A) DNA double-helix; (B) DNA melting curve showing thermal denaturation as temperature rises
Microheater device platform for cell cultures
Ligand-receptor interactions in response to a temperature gradient across the cell
Fractional occupancy of receptor sites as a function of the temperature difference across the cell