Abstract

Silicon Nanotechnology Meets Biology (Smaller and Wetter is Better)

Gregory Timp, Keough-Hesburgh Professor of Electrical Engineering & Systems Biology, The University of Notre Dame

According to Moore’s law, the scaling of silicon integrated circuits is supposed to reach the 5 nm-node sometime after 2020, although the schedule is still problematic due to the astronomical cost and atomically precise line-rules. On the other hand, biology has been performing cost-effectively using proteins the size of 5 nm (and smaller) that fold with atomic precision for 4.28 billion years now—it is a robust and proven technology, albeit wet. In this talk, it is argued that there is still “plenty of room at the bottom” for improving performance if silicon nanotechnology is adapted to biology. With silicon nanotechnology it is now within our grasp to create an interface to biology on a nanometer-scale. Three examples of such interfaces are proffered. The first is a liquid flow cell that works like an envelope made from 30 nm-thick silicon nitride membranes, which can hold and sustain living cells in medium and yet fits inside a Scanning Transmission Electron Microscope (STEM). In a STEM, the liquid cell can be used to visualize and track live cell physiology like a phage infecting a bacterium with nucleic acids at 5 nm resolution. The second is a nanometer-diameter pore sputtered through a silicon nitride membrane 10-nm-thick that can be used to transfect cells precisely with nucleic acids to affect gene expression in them and, under different bias conditions, detect protein secretions from single cells with single molecule sensitivity. The secretions inform on the cell phenotype and offer a molecular diagnosis of disease. Finally, the third interface is a sub-nanometer-diameter pore, which is about the size of an amino acid residue, in either silicon dioxide or silicon nitride membranes ranging from 6 to 10 nm-thick.  Sub-nanopores like this have been used to read the primary structure of a protein, i.e. the amino acid sequence, with low fidelity, but with single molecule sensitivity, vastly outstripping the sensitivity of conventional methods for sequencing such as mass spectrometry. Taken altogether, the prospects are dazzling for a new type of integrated circuit that incorporates biology with state-of-the-art silicon electronics.