Nanoscale pores function as membrane channels in all living systems, where they serve as sensitive electro-mechanical devices that regulate electrical potential, ionic flow, and molecular transport through the cell membrane. Studies of nanopore construction and their characterization for single molecule transport through solid-state membranes will lead to man-made cell membranes and single molecule detectors. A high-throughput solid state nanopore device that can probe and directly "read" electronically, at the single molecule level, the size, folding, and eventually the sequence of DNA and proteins, will dramatically alter the pace of biology and medical science. There are two major aspects of this research include studies involving :

(1) Fabricating molecular size solid state nanopores. Sculpting Nanoscale Structure with low Energy Ion Beams: To make nanometer pores in an insulating membrane such as silicon nitride, a combination of semiconductor device fabrication techniques followed by newly developed ways of controlling the lateral transport of matter across a surface on nanometer length scales, called ion beam sculpting are used. It starts with a double-side polished silicon wafer with 50-500 nm of low stress silicon nitride deposited on each side. A free standing Si₃N₄ membrane in the center of a small piece of the wafer is created using photolithography, reactive ion etching and wet chemical etching techniques. Next, ~100-nm hole is milled in this membrane using a focused Ion Beam machine or e-beam lithography.  Finally, the chip is placed in an Ion Beam Sculpting chamber where the large ~100-nm hole is controllably shrunk to a 1­10 nanometer pore. Fig.1 shows the Feed-back Controlled Ion Beam Sculpting System constructed in my lab in the University of Arkansas. This Ion Beam Sculpting system will not only provide a tool for making nanopores, but will also allow us to conduct basic materials sciences research to develop reliable control over the thickness, electrical properties and chemical activity of the nanopores.

(2) Developing solid state nanopore based single biopolymer detectors. Solid-state nanopores are mechanically robust, have tunable dimensions, tolerate broad temperatures, pH, and chemical variations, and are therefore ideally suitable for DNA and protein detection as well as integrated electronic device development. The research goal is to develop a nanopore technique to record single DNA and protein translocations in their denatured aqueous solution environment through a solid-state nanopore, probe the biopolymer’s length, diameter, secondary structure, charge, and eventually the sequence at high speed, high resolution, and low cost. This technology relies on the ability to draw single charged polymers in ionic solution through a solid state nanopore by an electrical field. The nanopore is designed to guarantee that each polymer traverses the detector in sequential, single file order. The detector then translates differences in the chemistry and physical properties of each successive nucleic acid or amino acid in the polymer into a characteristic electrical signal. To look at the primary structure of the DNA and proteins, single channel recordings of peptide translocation through solid state nanopores in ionic solution will be implemented and developed. The principle and idea of nanopore detection for single charged polymer is: a single nanopore in an insulating solid state membrane separates two ionic solution filled compartments, a voltage across the membrane is applied by a pair of electrodes. When polymers are added to the solution, translocation of an individual molecule through the pore will partially block the nanopore, a characteristic current blockage will be recorded (Fig.2). Each event is characterized by its average current drop amplitude: current blockade ΔI_b, and its time duration t_d (Fig.2 Bottom). The current blockade ΔI_b is proportional to the diameter of the molecule going through, the time duration t_d is proportional to the length and inversely proportional to the charge of the blocking molecule. We plan to study various aspects related to transport molecules across a nanopore including: 1) employing a combination of electric and fluorescence spectroscopy to observe single biopolymers in real time and under controlled conditions, 2) studying the physics of charged molecules driven through a solid state nanopore by an electrical field, 3) characterizing, counting and sizing charged DNA and protein molecules moving through the nanopores, and 4) developing new techniques to improve the time and space resolution of single molecule detection.