NIRT: Molecular Sensing and Actuation by CMOS Nonvolatile Charges with Independently Addressed Nanoscale Resolution Edwin C. Kan, F. A. Escebeo, A. Lal, J. R. Engstrom and D. A. Kyser Cornell University, Ithaca, NY Single-Electron Control at RT Floating-Gate-Based Sensors Wafer-binding/PDMS microfluidic Detection up to 1nA/1µs pulses Wierner Signal equalization Protein Adsorption Detection Bulk Potential Electrolyte Diffusive Layer (~25Å): second component of Gouy-Chapman-Stern model. ε r >78 Electrolyte Double Layer (~5Å): first component of Gouy- Chapman-Stern model. ε r >78 Streptavidin (~2-19Å): analyte protein for capture. Thickness increases as binding occurs. Assume ε r 10 Biotinylated BSA (~11Å). ε r 10 3-GPS (~14Å) ε r 11.8 Native Oxide (~26Å). ε r 4.0 C diff C EDL C strep C BSA C 3-GPS C oxide N R Molecules, cells and nano- engineered structures are all immerged in biochemical fluids. Anthrax pores (from Public Health Library) Gold nanoshells (from N. Halas, Rice) Functionalized SWNT (from H. Dai, Stanford) Examples of nano-engineered structures to build interface between molecules and inorganic devices. Notice that molecular selectivity is still provided by attached organic active ends. Charge surface of cytochrome B562 Blue: anion; red: cation; yellow: h-bond; white: neutral. Molecular structure of cytochrome B562 as an illustration The basic device structures for nano-scale molecular interactions based on electrostatic attractive and repulsive forces by CMOS nonvolatile charges. Our Unique Approach Molecular Simulation A generalized ensemble of M independent replicas are simulated using hybrid MC in which MD trajectories are carried out using CHARMM. Coarse Grain (a) Main-chain atoms of the llama HC-V domain solved by X- ray diffraction [Spinelly96]. The loops are shown as gray lines and proximal framework regions as black lines. (b) Schematic diagram of the simulation box for entropic trapping of DNA. Atomistic Real-time CνMOS monitoring of a single A431 cell on the sensing gate coated with poly-l- lysine. A431 is added to the DMEM in 10% FBS media solution after the surface is stabilized (1). The cell moves to the poly-l-lysine (2), seals (3) and immobilizes (4). EGF is then added (5), where receptor interaction is confirmed with fluorescence images. Cell life is monitored on the witness sample going through the same process by calcein staining. (1)(2)(3)(4)(5) V GS = 10V V DS = 5V A431 SEM after critical point dry A431 fluorescence image: 3 mins after adding EGF A431 fluorescence image: 15 mins after adding EGF Calcein staining to monitor cell life Cell A431 Sensing: EGFR DMEM/ FBS Stablize Cell moves to p-l-lysine Cell surface seals Cell immob- ilize EGF inter- action A431 Poly-l-Lysine Sensing gate Floating gate IDID V GS Control Gate Control Oxide Sensing Gate Tunnel Oxide Interpoly Oxide Source Drain Floating gate Sensing Gate Source Drain Control Gate Floating gate Interpoly Oxide Sensing Gate Pt Electrode Ag/AgCl Electrode Voltage Pulse Generator Microfluidic Chamber I d Wiener equalization Input I d Averaged C 60 1 E C60 1.3eV C 60 2 E C60 0.8eV C 60 3 E C60 0.8eV -0.55V -0.65V -3.36V -1.69V -1.77V -3.31V -3.27V Sensing Gate Native Oxide Silane Blocker Antibody Antigen Features 100% CMOS integration Specificity by sensing gate coating: pressure, proteins… Nonlinear response: high sensitivity and large range Noninvasive: no need of analyte reference electrode Applications In vivo sensing Monitoring cell events Specific protein sensing Sensor network Sensing Gates C MOS CMOS Transistor 1/f α behavior Noise floor DFT calculation C 60 Control Gate DrainSource Sensing Channel SiO 2 p++ Si Pd SWCNT Nanocrystal t top Control Gate Voltage (V) Drain Current (A) T=300K Long-term memory window Short-term single-electron sensitivity Initial memory window 1 m Nanotube Au leads Conventional Nanostructure Approach: Space Holder Motivation