Transcript Slide 1
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 10 ttop SWCNT Pd Pd SiO2 Gold nanoshells (from N. Halas, Rice) p++ Si Initial memory window after charging Short-term single-electron sensitivity -9 10 10 Functionalized SWNT (from H. Dai, Stanford) Long-term memory window T=300K Control Gate Source Charge surface of cytochrome B562 Blue: anion; red: cation; yellow: h-bond; white: neutral. -3 1 m Drain DFT calculation room temperature 0 2 2C60C 60 3 C 3- C60 C60 C60 60 EC60 EC60 EC60 E E EC60 C60 C60 ~ 0.8 eV ~ 0.8 eV0.8eV ~ 1.3 eV 0.8eV 1.3eV -10 -3.27V -3.31V -15 -20 -10 0 10 20 Vth Vth0 Atomistic H1,T1 H2,T2 ... Hi,Ti ... HM,TM 30 40 50 -3.36V hybrid MC CHARMM CHARMM hybrid MC CHARMM hybrid MC CHARMM Coarse Grain H1 CT 0.02 0.01 0 0.05 0.1 0.15 0.2 Captured mass ( g/cm 2) Floating gate CMOS Transistor Wafer-binding/PDMS microfluidic 2.00E-05 Detection up to 1nA/1µs pulses Wierner Signal equalization 1.80E-05 Mixture 0.5 M NaCl 0.05 M KCl 5 (1) Sensing Gates Ag/AgCl Electrode Pt Electrode 0.0 4 Microfluidic Chamber 3 Ideal calibration curve 15 10 5 Voltage Pulse Generator Sensing Gate 1/f α behavior Noise floor 10 10 -5 Sampled data 1/f spectrum -10 1/f2 spectrum 10 0 0 5 10 15 -2 10 0 Log frequency (Hz) 20 Ellipsometer: analyte thickness (Angstroms) A431 Poly-l-Lysine Sensing gate Floating gate Cell Cell moves to surface p-l-lysine seals (2) Calcein staining to monitor cell life Cell immobilize EGF interaction (4) (5) (3) 1.40E-05 1.20E-05 1.00E-05 Addition of EGF in Culture media (2ul Drop) concentration 5ug/ml 8.00E-06 6.00E-06 H2 Fit for measured data A431 fluorescence A431 fluorescence image: 15 minstime after image: 3 mins after the current Monitoring over adding EGF adding EGF DMEM/ FBS Stablize 1.60E-05 2 Measured data Interpoly Oxide Drain 2.5 0.25 20 VGS A431 SEM after critical point dry CMOS In vivo sensing Monitoring cell events Specific protein sensing Sensor network ID Q Vcg Ccg Vd C gd Vs C gs C sg Vsg 1 A generalized ensemble of M independent replicas are simulated using hybrid MC in which MD trajectories are carried out using CHARMM. 0.03 Id Current hybrid MC ... 100% CMOS integration Specificity by sensing gate coating: pressure, proteins… Nonlinear response: high sensitivity and large range Noninvasive: no need of analyte reference electrode Cell A431 Sensing: EGFR Control Gate ... 0.04 Sensing Gate Control Gate Sensing Gate Interpoly Oxide Control Oxide Floating Tunnel Oxide gate Source Drain Signal change from event Measured data Fitted data 0.05 0 Source DMEM in FBS (9ul) 4.00E-06 ADDITION of A431 in culture media (5ul) VGS = 10V Series1 VDS = 5V 2.00E-06 H3 5.0 (a) Main-chain atoms of the llama HC-V domain solved by Xray 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. Normalized d1i-mC Norm SG (d1i-m) 4.5 4.0 3.5 0.7 polysilicon poly(vinyl acetate) poly(vinyl butyral) poly(ethylene -co- vinyl acetate) poly(vinyl chloride) Id Wiener equalization 0.6 0.00E+00 0 0.5 Signal (V or A) Hybrid MC with Multi-Dimensional Replica Exchanges 1 (Q C gsVs C gd Vd ) CT CT (Cox || Cdep ) Cb C gs C gd C sg VFG Free Energy Lanscape Features Floating-Gate-Based Sensors Molecular Simulation Native Oxide (~26Å). εr≈4.0 Applications 0.06 -1.77V -5 Coxide 1000 1200 1400 1600 1800 2000 Time(sec) -1.69V Control sample 1- 11% coverage capture Control data 3-GPS (~14Å) εr≈11.8 0.3 Gate Voltage (V) -0.65V 5 1 C3-GPS 0.25 -0.55V Programming Voltage [V] Hamiltonian and Temperature 0 Sensor response (Vrms) The basic device structures for nano-scale molecular interactions based on electrostatic attractive and repulsive forces by CMOS nonvolatile charges. -2 -1 Control Gate Voltage (V) Au leads 10 VFB [V] Molecular structure of cytochrome B562 as an illustration Sensing Channel 0.4 Biotinylated BSA (~11Å). εr≈10 69% coverage capture 0.35 Add analyte C60 Our Unique Approach Cstrep CBSA Au leads 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. CEDL after discharge -10 Electrolyte Diffusive Layer (~25Å): second component of Gouy-Chapman-Stern model. εr>78 Electrolyte Double Layer (~5Å): first component of GouyChapman-Stern model. εr>78 Streptavidin (~2-19Å): analyte protein for capture. Thickness increases as binding occurs. Assume εr≈10 Cdiff Log magnitude (Vrms) Anthrax pores (from Public Health Library) -8 Drain Current (A) N Nanocrystal Molecules, cells and nanoengineered structures are all immerged in biochemical fluids. Bulk Potential Antigen Antibody Blocker Silane Native Oxide Sensing Gate Sensor Signal Magnitude (Vrms) Conventional Nanostructure Approach: Space Holder R Protein Adsorption Detection Single-Electron Control at RT Sensor: detected thickness (Angstroms) Motivation 1000 2000 3000 4000 5000 6000 Time in seconds 0.4 3.0 2.5 0.3 2.0 Id Averaged 0.2 1.5 1.0 Input Pulse Input 0.1 Id Averaged 0.5 0 0.0 1 DI water 50 2M 3 0.005M Sample Fluids 4 0.05 M 5 0.5M Id Equalized -2 -1 Time0(10-4 s) 1 2 -4 x 10 Real-time CνMOS monitoring of a single A431 cell on the sensing gate coated with poly-llysine. 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. 10 2