1. NER: Nanoscale Sensing and Control of Biological Processes Objective: To provide a microelectronic and microfluidic environment as a test bed for nanoelectronic / biological interfaces; to sense and control low-level charge signals arising from redox events at nanoelectrode complexes in solution Approaches and Contributions: Design and calibration of a micro-cyclic voltammetry flow-chip prototype Target DNA hybridization detection at the micro-cyclic voltammetry flow-chip Molecular assembly of a redox enzyme system by a metallized peptide at the three-microelectrode cell Development and characterization of nanoelectrode array grown on a Si substrate Flow-through nanopore membrance design for efficient in situ electrochemical synthesis and detection Gold Nanotubes as Flow-Through Bioreactors for Microfluidic Networks Napat Triroj and Rod Beresford Brown University, Providence, RI Napat Triroj and Rod Beresford Brown University, Providence, RI Micro cyclic voltammetry measurement Molecular assembly of Npx system Analyte solution: 10 mM K 3 Fe(CN) 6 in 1 M KNO 3 0.20.40.60.81.0 -2.0 -1.5 -0.5 0.0 0.5 1.0 1.5 2.0 Peak current (nA) (Scan rate) 1/2 (V/s) 1/2 cathodic anodic DNA hybridization detection 0.80.60.40.20.0-0.2 -2.5 -2.0 -1.5 -0.5 0.0 0.5 Npx-PepCo-AuNP in KAc Npx-PepCo-AuNP in KAc + H 2 O 2 NPx-PepCo-AuNP in KAc + NADH Npx-AuNP in KAc Current (nA) Potential vs. Ag/AgCl (V) Nanoelectrode array fabrication onto working electrode Analyte I/O Digital I/O The functionality of the microfluidic three- electrode cell is confirmed: - formal potential is close to the literature values - peak current is proportional to (scan rate) 1/2 An increase in the electrocatalytic charge upon hybridization of the target DNA present at low- concentration Analyte: 27 µM Ru(NH 3 ) 6 3+ and 2 mM Fe(CN) 6 3- 2 µM thiolated ssDNA, 500 nM target DNA Current density: 3.9 mA/cm 2 compared to 0.21 mA/cm 2 at a bulk gold electrode In collaboration with Prof. Joanne Yeh at University of Pittsburgh Medical Center Collaboration with Prof. Shana O. Kelley, University of Toronto A self-assembled system consists of NADH peroxidase (Npx) enzyme, a metallized peptide, and a gold nanoparticle onto a microfluidic three- electrode cell Detection of the changes in redox signals in the presence of H 2 O 2 and NADH Electrode array process Assemble PDMS gasket to electrode substrate Cl 2 plasma treatment to convert part of Ag to AgCl Etch Si 3 N 4 using CF 4 plasma PECVD of Si 3 N 4 E-beam evaporation of Ti/Au and lift- off PR After Cl 2 plasma of Ag and lift-off Working electrode surface area: 9 µm 2 30 µm Fabrication results Micro cyclic voltammetry flow-chip prototype fabrication Mask design Completed flow-cell chip Integration: Chip package  Si signal processors  nanoelectrode array  self-assembled linker system  biomolecular target Collaboration with Prof. Jimmy Xu at Brown Univ. An on-chip “biology-to-digital" sensing and control system Nanowire array grown in FIB-patterned Al 2 O 3 ; wire diameter less than 50 nm Nanocrystal array grown from Co catalyst in FIB-patterned Al 2 O 3 Silicon microelectronic signal processing and control Flow network chip Flip and bond Biosensor electronic chip Flow-channel network Electrochemical sensing module In situ monitoring, sensing, control, and actuation of biomolecular reactions Collaboration with Hitomi Mukaibo and Charles R. Martin, University of Florida Andres Jaramillo (undergraduate), Florida State University Collaborators: Jimmy Xu, Brown University ~ Charles R. Martin, University of Florida ~ Shana O. Kelley, University of Toronto ~ Joanne I. Yeh, University of Pittsburgh 1 μm Au dot Collaboration with P. Jaroenapibal, University of Pennsylvania Ultra-sensitive integrated enzymatic detector arrays In a conically shaped nanotube, flow from base to tip is continually focused to the tube wall, resulting in high conversion efficiency Resistance to flow can be adjusted at will by controlling the base opening, tip diameter, and cone angle Base opening Tip opening Conical nanopore PET membrane fabricated by Martin group Membrane sections captured between orthogonal channels in the chip assembly process Electrical connection to continuous deposited Au film on the PET membrane Planar working electrode also in each channel as a control Coupled channels: analyze → synthesize → analyze membrane contact pad Electrode cell in glass: channel depth = 12 μm area of WE = 2.5 x 10 -5 cm 2 Continuity of Au trace into channel Modeling and Simulation of Nanoelectrochemistry r0r0 T Voltage Electrocatalytic model design Time Large and positive charge number of O enhances migration current at nanoelectrode Large and negative charge number of Z suppresses the current plateau and enhances cathodic peak Outlet PET membrane Glass channel PDMS channel Inlet