Micro Manipulator Array for Nano-bioelectronics Era

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Micro Mnipultor Arry for Nno-bioelectronics Er K. Suzuki, Y. Nruse, H. Funki, K. Ity nd S. Uchikog Advnced Electron Devices Lbortory Corporte Reserch nd Development Center TOSHIBA Corportion Copyright 2002 Toshib Corportion. All rights reserved.

OUTLINE Introduction Device Structure Physicl Interction Experiments & Results Future Visions Summry 2 / A Symposium on High Performnce Chips / August 22, 2006

MOTIVATION 3 / A Symposium on High Performnce Chips / August 22, 2006

THE APPROACH Applied field of nnotechnology Resources & Energy Communictions & Electronics Biotechnology Medicl cre & Helth cre Chemicl Appliction for next genertion medicl cre Dignosis Micro-TAS DNA chip Tretment DDS Physicl Antibiotics Approch s electronics compny Physicl This leds to the promising future technology of "tilormde medicl tretments" corresponding to the needs of the individul. 4 / A Symposium on High Performnce Chips / August 22, 2006

PHYSICAL ANTIBIOTICS Procryotic cell (bcteri) Cell wll Cell membrne Cytoplsm Internl pressure Grm-positive nerobic 20P Grm-negtive nerobic 8P Attck!! Physicl energy Nnoprticle Peptidoglycn Mechnicl vibrtion where high surfce temperture is obtined by the therml boundry theory is one method by which nnoprticles cn be introduced. 5 / A Symposium on High Performnce Chips / August 22, 2006

ADSORPTION OF NANOPARTICLES Temperture The nnoprticle is induced to the high temperture re by the mechnicl vibrtion. Nnoprticle Therml boundry lyer (flow velocity =>smll) Surfce Temperture of = T f + ( 2g / 3λh ) b /( + T f nnoprticle b) Bcteri η ~ M ω / C x Flow speed Therml boundry lyer (flow velocity =>lrge) Externl Vibrtion 6 / A Symposium on High Performnce Chips / August 22, 2006

7 / A Symposium on High Performnce Chips / August 22, 2006 Bio-fluid temperturet f r Nnoprticle Temperture:T 1 () T 2 (+b)=t f b Therml boundry lyer A nnoprticle in sphericl coordintes ADSORPTION OF NANOPARTICLES (1) (2) (3) (4) (6) (7) (5) ) /( ) /3 ( ) ( ) ( ) ( ) ( /3 4 4 ) / ( /3 4 4 ) / (, / ) ( 0, / ) ( 2 1 2 1 2 3 2 2 3 2 1 2 1 b b g T T T T T b T g dr dt g dr dt b r D r C r T r B r A r T h f f r h r + + = = = + = = + < < + = < < + = = = λ π π λ π π λ T 1 (r): Therml distribution (nnoprticles) T 2 (r): Therml distribution (stgnnt lyer) : Rdius of the nnoprticles b: Width of the stgnnt lyer λ : Therml conductivity (nnoprticles) λ b : Therml conductivity (biofluid) g: Energy genertion rte in the nnoprticles T f : Flow temperture of the biofluid T 1 (): Surfce temperture of the nnoprticles Prmeters

M x = C ( y ) VIBRATION EFFICIENCY x x M x + Cx x = M y x = A e y = B e jωt jωt (3) (4) (1) (2) ( C x / M ω) Cx = k BT / η ~ M ω / 2 = η 2 D (6) C x 1 (7) (5) Prmeters M: Motion for mobile protein with mss C x : Viscous dmping constnt ω: Angulr frequency of externl mechnicl vibrtion η: Vibrtion efficiency s the rtio of the bsolute vlue D: Diffusion constnt k B : Boltzmnn constnt T: Absolute temperture Indictor for designing the in vivo nd In vitro pplictions. 8 / A Symposium on High Performnce Chips / August 22, 2006

DEVICE STRUCTURE Dish ; 20µm x 20µm 8-inch SOI wfer (0.25-µm design rule) 125Å 400Å 625µm Chip size; 6mm x 6mm SOI BOX Si Sub. 30µm Circuit regions Diode 30µm Spirl rm (Inductor) Mechnicl diphrgm ; 4mm x 4mm (130 x 130 dishes) CMOS+MEMS process Collision energy =>Vibrting Electric heting energy =>Joule heting Mechnicl diphrgm (SEM imge) 9 / A Symposium on High Performnce Chips / August 22, 2006

ELECTROSTATIC VIBRATING C 8 F 13 H 4 C 8 F 13 H 4 C 8 F 13 H 4 Si O Si O Si O O O Silic prticles (>1µmϕ) Culture medium Yest cells (5µmϕ) Hydrophobic coting 35 Vibrtion Diphrgm (SOI) Displcem ent[µm ] 30 25 20 15 10 5 0 0 5 10 15 20 25 30 35 40 Si Sub. Applied voltge [V] Yest cells re chosen for testing mteril since they hve similr chrcteristics to typicl bio-cells. 10 / A Symposium on High Performnce Chips / August 22, 2006

FABRICATION PROCESS 1) Spirl rm region Dish region Signl line Al SOI Poly-Si 3) TEOS (multi lyer) STI BOX Si sub. 2) 4) Diphrgm region Anti stiction coting (1) The micro dish nd spirl rms re fbricted by CMOS processing (0.25-µm design rule). (2) The TEOS lyer is etched down to the silicon substrte by RIE, nd the formed lttice is netly rrnged in 30-µm pitch. (3) A cvity is formed by isotropicly etching the silicon substrte using XeF 2 gs. (4) A hydrophobic coting is deposited using C 8 F l3 H 4 SiCl 3 nd H 2 O gses. 11 / A Symposium on High Performnce Chips / August 22, 2006

Lser microscope Opticl microscope INTERACTION BETWEEN CELLS & PARTICLES Yest cell & Silic prticle After excittion (30V 1kHz signl) Silic prticle Yest cell Yest cell Silic prticle Cell wll Cell wll Yest cell Cytoplsm Cytoplsm Silic prticle Silic prticle Yest cell Cell Wll Cytoplsm Cell Wll Prticle Cell Wll 12 / A Symposium on High Performnce Chips / August 22, 2006

HEATING OF HIGH-PRESSURE CYTOPLASM USING GROUPS OF NANOPARTICLES Nnoprticle Cytoplsm Cell wll 20P DNA Silic prticle Molr elevtion of boiling point Cytoplsm : steriliztion temperture 150~200ºC Yest cell Cell wll Osmotic pressure : P=k*C*T [mol/l] [k] (W.Pfeffer) 13 / A Symposium on High Performnce Chips / August 22, 2006

DEVICE STRUCTURE Dish ; 20µm x 20µm 8-inch SOI wfer (0.25-µm design rule) 125Å 400Å 625µm Chip size; 6mm x 6mm SOI BOX Si Sub. 30µm Circuit regions Diode 30µm Spirl rm (Inductor) Mechnicl diphrgm ; 4mm x 4mm (130 x 130 dishes) CMOS+MEMS process Collision energy =>Vibrting Electric heting energy =>Joule heting Mechnicl diphrgm (SEM imge) 14 / A Symposium on High Performnce Chips / August 22, 2006

LOCAL HEATING AT MICRO DISH I-V chrcteristic versus dish temperture (In tmosphere) Temperture increse of the micro dish versus If If(A ) 0.01 0.001 0.0001 1E-05 1E-06 1E-07 1E-08 1E-09 1E-10 1E-11 1E-12 1E-13 1E-14 0 2 4 6 8 10 12 Vf(V ) G th :2.0E-6 (W/K) C th : 3.0E-9 (J/K) 1E -14 1E -12 1E-10 1E-08 0.000001 0.0001 0.01 1 0.1 T = VfEIf G th If(A ) 10000 1000 100 0.01 0.001 0.0001 0.00001 { 1 exp( tg th^c th )} 10 1 ƒ Tsh(K) 15 / A Symposium on High Performnce Chips / August 22, 2006

TURN ON CHARACTERISTICS Micro Dish Tem perture Increse(K) 1.00E+03 1.00E+02 1.00E+01 1.00E+00 0 1 2 3 4 5 6 7 8 9 10 1.00E-01 1.00E-02 1.00E-03 If=1nA If=10nA 1.00E-04 If=100nA If=1ƒÊA If=10ƒÊA If=100ƒÊA Time(ms) Thermic effect of micro dish (10ºC) by FEM 16 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EXPERIMENT I. DC power supply Blckbody furnce V dd V L MEMS V ss Aperture (Reference temperture ) Therml sensing DC power supply IR-cmer Out Reference trget (Low temperture) 50 100 150 200 33 32 31 30 29 Reference trget Chip(MEMS Are) ( temperture) 250 28 300 27 350 26 400 25 450 24 100 200 300 400 500 600 17 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EXPERIMENT RESULTS I. ºC V L 0V V L 1.5V V L 2.0V IR cmer imge 1mm 1mm 1mm Het distribution nlyze 18 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EXPERIMENT RESULTS I. -Therml difference- - - ºC Het effect : pprox. 9.7 ºC 19 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EXPERIMENT II. I. Circuit configurtion Mesurement configurtion Dt genertor V reg CLK (Pulse) Blckbody furnce V dd V L MEMS V ss Aperture (Reference temperture ) DC power supply IR-cmer Therml sensing Out 20 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EXPERIMENT RESULTS II. 1 Pulse width : 100ms 1sec 2sec 3sec ºC IR cmer imge Het distribution nlyze 1mm 1mm Room Temperture : 25.6ºC Heted Micro-dish Temperture : 62.6ºC 1mm 21 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EXPERIMENT RESULTS II. -Video movies- Pulse: 1s Pulse: 100ms Pulse: 50ms Pulse: 10ms Pulse: 1ms 22 / A Symposium on High Performnce Chips / August 22, 2006

HEATING EFFECT COMPARISON High heting efficiency 23 / A Symposium on High Performnce Chips / August 22, 2006

REMARKS (JOULE HEATING) Heting of the whole micro dish rry nd just n rbitrry portion of the micro dish ws demonstrted. Rpid temperture switching on micro second order ws confirmed. More thn twice the het effect ws chieved in heting n rbitrry portion compred with heting the whole micro dish. (bsed on efficiency) 24 / A Symposium on High Performnce Chips / August 22, 2006

ADVANCED DEVICE VCLK T Tsh Tcell Tsh Tsub t Exothermic biologicl rections will cuse temperture spikes in the vicinity of the rection which in term cuses the nerest diode to red higher temperture. Scnning the rry of temperture sensors cross the chip will identify the prticle X-Y position of the rection. 25 / A Symposium on High Performnce Chips / August 22, 2006

FUTURE VISIONS Ptient Vibrtion, Heting etc. New cell engineering 26 / A Symposium on High Performnce Chips / August 22, 2006

SUMMARY We hve developed micro mnipultor rry using novel MEMS-bsed structure. We lso demonstrted direct physicl control of the interction between yest cells nd silic prticles in liquid for the first time. The dsorption of the prticle to the cell ws demonstrted using vibrtionl energy, nd Joule heting energy ccording to externl excittion. These results show potentil impct in medicl fields such s physicl ntibiotics nd cell tretments nd next genertion bio-electronics schemes. 27 / A Symposium on High Performnce Chips / August 22, 2006