Nanowire FET Biomolecular Sensors

Transcription

1 Nanowire FET Biomolecular Sensors Mark Reed Yale University Departments of Applied Physics and Electrical Engineering Yale Institute for Nanoscience and Quantum Engineering with: Eric Stern, David Routenberg, Erin Steenblock, Alek Vacic, Nitin Rajan, Prof. Tarek Fahmy Thanks to: Jin Chen, James Klemic, Daniel Turner-Evans, Pauline Wyrembak, Cathy Jan Labs of Profs. Ronald Breaker, Andrew Hamilton, Tarek Fahmy 1

2 What I won t talk about today plasmonics mesoscopics nanowire materials & devices DNA sequencing devices molecular electronic transport, IETS physics of scaled devices 2

3 Current Macromolecular Sensing Labeled sensing DNA sequencing, radiotag Unlabeled sensing DNA array, fluor ELISA: Indirect fluor Surface plasmon resonance Suspended cantilever Electrical : ISFET 3

4 Nanowire biosensors (unlabeled detection) PSA PSA PSA antibody Linker (C. Zhou, USC) PSA ISFETs detection limits typically ~ µm 1 I di dq ~ 1 r Au/Ti SiO 2 Si 390 I (na) 385 NW/SWNT Buffer BSA PSA Time (s) In 2 O 3 NW nm diameter GaN NW 4

5 Silicon-on-insulator (SOI) CMOS Nanowires I SD (A) K, dry 25nm SOI V G =-40V Nature 445, 519 (2007) V SD (V) V G =0V 5

6 p-type accumulation mode (backgate) -3 V G =1V 300K, dry w=50nm, t=25nm V G =-40V I SD (A) 100n 1n 10p V SD =-1V I SD (A) f 1f V GD (V) V SD (V) Fully depleted; n 0 ~ 1x10 15 cm -3 µ = 54 cm 2 /V-s 0V µ max = 139 cm 2 /V-s Mobility (cm 2 /Vs) w = 300 nm t = 25 nm Temperature (K) Hall Drift 6

7 1/f noise of nanowires SnO 2 InAs ITRS S I I 2 = α f H N Si SOI NW α H = 1.3 x

8 NW Sensitivity Scaling with Size : ph Sensing NB device RIE device I SD (A) 100n 10n large small Sensitivity 20 I I SD,0 V 2 αn = R n SD SD Inverse Radius (µm -1 ) 0 s Time (s) large: w = 1000 nm; t = 80 nm small: w = 100 nm; t = 25 nm Nernst potential = 60mV ph Subthreshold slope = 60mV decade max. response is 1decade ph 8

9 Fluid Considerations Nano Lett 5,, 803 (2005) 1E12 1E10 J d C dz z = D + 2 u z C 0 # Molecules/Min 1E x E-4 1E C 0 (M) Silicon-specific functionalization x Nonspecific functionalization x = microfluidics Science 293, 1289 (2001) x = mixer (resorvoir) Nature 445, 519 (2007) 9

10 n n n n Biotin-Avidin & Streptavidin Sensing analyte receptor (biotin) p-type accumulation mode, biotinylated NW device avidin u positive charge u current decrease streptavidin u negative charge u current increase poly(ethylene glycol) (PEG)-ylated device, quenched avidin controls I SD (A) 300n 200n 100n nm protein in 0.1X PBS (λ D ~ 2.2 nm) Time (sec) Nature, 445,, 519 (2007) Streptavidin Quenched S-Av PEGylated Avidin 10

11 Sensitivity: Concentration Dependence Normalized I SD (A) nm 10 pm 100 fm 10 fm n initial S/N ~ 140 (@10fM) <100 am limit (< 3 fg/ml) (11 am = 30 molecule per mm 3 ) DC, ambient Time (sec) 11

12 DNA sensing: criss-cross S D Capture1 is the complementary strand of Probe1; Capture2 is the complementary strand of Probe I SD (A) Time (sec) Probe 1 Probe 2 I SD (A) n Time (sec) Probe 1 Probe 2 Surface: Capture1 Surface: Capture2 S D 12

13 Debye Screening Considerations b 1.0 add S-Av.01X t = 0:.01X Alone S-Av (.01X) λ D = 1 ( ) 2 4πl z ρ 1/ 2 B for 0.1 mm PBS, λ D ~ 2.2nm i i i I SD (A) 800.0n.01X.1X 1X.01X TCEP (cleave).01x 600.0n Time (s) Control no S-Av.1X 1X Stern et al, Nano Lett. 7,, 3405 (2007) 13

14 Protein Assay: Antibody-Antigen Specificity Surface: α-mouse-iga 275n 250n 225n mouse-iga mouse-igg PEGylated I SD (A) 200n 175n 150n 125n 100 fm 100n Time (sec) 100 fm mouse-igg/iga in 1.5 mm bicarbonate (λ( D ~ 6.8 nm) 14

15 Unlabeled Cellular Detection n Most cells (including pathogenic) release H + in response to specific stimulation Nat Rev Immunol 3 (2003)

16 Real-time live cellular response T-lymphocyte activation 1 C57BL/6 (B6) mouse splenocytes I SD I SD (A) 800n 600n anti-cd3 to: normal inhibited (Genistein) H + time 400n Time (s) Real-time measurement of cell immune response dynamics 16

17 Transgenic peptide-specific MHC T-cell response OT-1/2C transgenic murine CD8 + T-cells H-2K b -SIY OT-1 2C X OT-1 1 reacts to H-2KH b -SIIN, not H-2KH b -SIY 2C reacts to H-2KH b -SIY, not H-2KH b -SIIN H-2K b -SIIN X I SD (A) OT Time (sec) H-2K b -SIIN H-2K b -SIY I SD (A) n 600.0n H-2K b -SIIN 400.0n H-2K b -SIY Time (sec) 2C Model system for detecting autoimmune diseases and cancer Stern et al, Nano Lett. 8,, 3310 (2008). 17

18 Summary n CMOS-integrable NWs u Label-free sensing to am resolution Enables system-level integration u Macromolecular assays n Real-time cellular immune response u Applicable to simple, point-of of-care diagnostics (all simple DC, ambient) u Immune response dynamics n Rich area for novel device designs, applications Altura Diagnostics n The challenge: sensing with physiologic solutions (blood) 18