NanowireSensor (Nano-Tera)

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There is nowadays a growing need for sensing devices offering rapid and portable analytical functionality in real-time as well as massively parallel capabilities with very high sensitivity at the molecular level. Such devices are essential to facilitate research and foster advances in fields such as drug discovery, proteomics, medical diagnostics, systems biology or environmental monitoring.

In this context, an ideal solution is an ion-sensitive field-effect transistor sensor platform based on silicon nanowires to be integrated in a CMOS architecture. Indeed, in addition to the expected high sensitivity and superior signal quality, such nanowire sensors could be mass manufactured at reasonable costs, and readily integrated into electronic diagnostic devices to facilitate bed-site diagnostics and personalized medicine. Moreover, their small size makes them ideal candidates for future implanted sensing devices. While promising biosensing experiments based on silicon nanowire field-effect transistors have been reported, real-life applications still require improved control, together with a detailed understanding of the basic sensing mechanisms. For instance, it is crucial to optimize the geometry of the wire, a still rather unexplored aspect up to now, as well as its surface functionalization or its selectivity to the targeted analytes.

This project seeks to develop a modular, scalable and integrateable sensor platform for the electronic detection of analytes in solution. The idea is to integrate silicon nanowire field-effect transistors as a sensor array and combine them with state-of-the-art microfabricated interface electronics as well as with microfluidic channels for liquid handling. Such sensors have the potential to be mass manufactured at reasonable costs, allowing their integration as the active sensor part in electronic point-of-care diagnostic devices to facilitate, for instance, bed-side diagnostics and personalized medicine. Another important field is systems biology, where many substances need to be quantitatively detected in parallel at very low concentrations: in these situations, the platform being developed fulfills the requirements ideally and will have a strong impact and provide new insights, e.g. into the metabolic processes of cells, organisms or organs.

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NanowireSensor (Nano-Tera)

  1. 1. Nanowire SensorIntegrateable Si Nanowire SensorPlatform for  Ion‐ and BiosensingPI: Christian SchönenbergerDepartment of Physics andSwiss Nanoscience Insitute@ University of Basel 1
  2. 2. More than Moore  scalable sensing chip 2
  3. 3. Bio- / chemical Sensor a device that can detect molecules in a with some specificity how can this information be read ? mechanically a) mass change (QCM) b) strain (cantilever) optically a) labelled (DNA chip) b) refractive index c) Plasmonics electrically a) impedance spectroscopy b) CV spectroscopy c) potentiometric (e.g. zeta potential) 3
  4. 4. Potentiometric Sensing IS-FET P. Bergveld / Sensors and Actuators B 88 1–20 (2003) 4
  5. 5. Ion Sensitive FET (IS-FET) channel conductance (i.e. threshold) depends on gate charge e.g. heparime binding on protamie p-channel, threshold regime - - - (source-drain current) - SHIFTsource drain - - - (gate potential) 5
  6. 6. Electronic Biochip Concept Bergveld and others C. Lieber et al. 6
  7. 7. Project fabrication technology (PSI, Basel, EPFL) surfacefunctionalization (FHNW, ETHZ Basel‐Pharma) on-chip and system microfluidics simulation integration (ETHZ, Basel) electrical characterization (D‐BSSE, EPFL) and biochemical validation (all) 7
  8. 8. NW fabricationp-type (100) SOI > 30 nm SiO2 ~ 10 – 25 nm Si 40 – 85 nm buried SiO2 (BOX) 350 nm Si handle wafer 300 nm Cr mask  HSQ resist contact masks  ion implantation 70 nm SiO2 plasma etching in CHF3 Al contact annealing Si wet etching in TMAH 8
  9. 9. NW fabrication accumulation inversion (non‐implanted, Al‐contacts) 9
  10. 10. NW fabricationNovel fabricatedGAA (gate all around) SiNWs SS = 62 mV/dec Ion/Ioff = 105-106 S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL 10
  11. 11. NW fabrication A partially double-gated fin field effect transistor (DG-FinFET) is the electronic sensing architecture. _ _ __ _ _ _ opera on → enhancement mode insulator Layer → HfO2, tins = 5 nm,  poly‐Si Gates → wg = 25 nm, hg = 50 nm fin Body → hSi = 100 nm, wSi = 50nm doping → Na = 5×1016 S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL 11
  12. 12. Isolation SiO2 surface leaks Al2O3 no leakage HfO2 in progress liquid channel Si NW sealing layer 12
  13. 13. Results (pH sensing)liquid-gate back-gate VthO. Knopfmacher et al. Nano Lett. 10, 2268 (2010) 13
  14. 14. Result: Modelling ∆G ≈ 40 nS ∆Vth ≈ 400 mV ∆Vth = 300 mVO. Knopfmacher, A. Tarasov, W. Fu, M. Wipf, B. Niesen, M. Calame, C. Schönenberger, model by P. Livi et al. D-BSSENano Letters 10, 2268 (2010) 14
  15. 15. Results: Nernst limit vs liquid gate vs back gate µ ¶ kT ±Vl g¡ sh i f t = ±pH B 2:3 ¢® q µ ¶ Cdl ;ox corrected ±Vbg¡ sh i f t = ±Vl g¡ sh i f t Cbg O. Knopfmacher et al. Nano Lett. 10, 2268 (2010) 15
  16. 16. Results: Noise Measurements C. Beenakker and C. Schönenberger, Physics Today, Vol. 56, issue 5, page 37-42 (2003) FFT Tarasov et al. , APL, 98, 012114, (2011) 16
  17. 17. Results: Noise Measurements threshold noise: 400 ppm of pH Tarasov et al. , APL, 98, 012114, (2011) 17
  18. 18. Functionalized surface R1=NH2, Cl, CH3 bare alumina: 45‐55 mV/pH a) APTES: 26 mV/pH b) CPTO+APTES: 17 mV/pH c) after UV ozone:  32 mV/pH d) alkane with R=CH3:  0 mV/pH 18
  19. 19. Biosensing Affinity Determination of Receptor-Ligand Interaction (lectin-sugar interaction) Human Asialoglycoprotein-Receptor (hASGP-R) ligand + cargo and the ligand GalNAc (N-acetyl-galactosamine)adapted from the thesis ofClaudia Riva, Uni Basel 2007 ASGP-R plays an important role in the endocytosis in liver cells ASGP-R is a glycoproteins that binds to Gal terminal GalNAc immobilized on ASGP-R silicon nanowire H OH N O O SiNW Si O O with binding 2 AcHN O OH OH site HL-1 CRD H OH N O O Si O O AcHN O 2 OH OH H OH B. Ernst et al. Si N O O O O AcHN O 2 OH OH 19
  20. 20. Biosensing add ASGP receptor glycoconjugate Gal frequency change  (Hz)         R= GluNAc (glucose) 1 GalNA (galactose) 2 3 6 5 time (min) QCM test experiment: Change in 4 frequency for the GalNAc ligand (yellow) and negative control having the GluNAc ligand (grey) 20
  21. 21. Biosensing strongly lectin binding glycoconjugate add ASGP receptorR= Lectin, 20 g/ml frequency change  (Hz)          inactive structure Changes in the frequency of an oscillation quartz crystal upon binding of the asialoglycoprotein to the glycoconjugate NW 21
  22. 22. Biosensing add ASGP receptor strongly lectin binding glycoconjugate inactive glycoconjugate structure 22
  23. 23. Metallic Nanowires Solid nanowire array Particle based nanowire array 23
  24. 24. Metallic Nanowires Combined optical and electrical measurements in response to an  150mM NaCl applied solution gating voltage of ±500 mV in 1 mM NaCl. Na+ Cl-V0V-V+ MacKenzie R., Dielacher B. et al., submitted 2010 24
  25. 25. Advanced Nanowire Chip and Flow Cell• 4 electrodes per nanowire region• Integrated platinum counter electrodes• Integrated silver reference electrodes• SU-8 for isolation• Openings to each nanowire region channel CE / Ag‐ref 25
  26. 26. Advanced Nanowire Chip and Flow Cell 26
  27. 27. Advanced Nanowire Chip and Flow Cell 27
  28. 28. Combined metall & Si device redish = Au on top Si-nanowirediameter: ~40nmheight: Au ~5nm 28
  29. 29. Upscaling quarter of 8``SOI‐wafer (supplier Soitec) for implantation: 20 x 20 mm2 chips are required 100 mm => containing four devices (1) 20 mm 2 9 10 20 mm100 mm 8/1 8/2 3 8 16 8/4 8/3 4 7 12 15 5 6 13 14 17 number of  number of  20x20mm2 device chip 16 x 4 devices with 48 FETs each= 3‘072 FETs (written at once with e-beam) 29
  30. 30. Upscaling 30
  31. 31. Upscaling 31
  32. 32. Upscaling & Integration 32
  33. 33. Integration• 16 nanowires can be interfaced in parallel• Voltage across each nanowire is kept constant, and the current flowing through is measured• The measured current is then digitized• Two different analog‐to‐digital converter architectures are used (12 bits resolution)• Current range: 1 nA to 5 μA 33
  34. 34. Readout The nanowire drain‐source voltage is  clamped. Differential measurement using a  reference and a sensing  nanowire. sigma‐delta converter compact and power‐efficient implementation. Shepherd, L. et al., ``A novel voltage-clamped CMOS ISFET sensor Interface”, ISCAS 2007 34
  35. 35. CMOS interface: first prototype chip Contacts for  integrated gold  nanowires Deposited by  PSI in a CMOS 3.4 mm post‐processing  converters procedure Voltage buffers Sigma‐Delta modulators I to F Fabricated in  0.35μm CMOS  technology PADS 35 4 mm
  36. 36. Summary demonstrated reproducible and hysteresis‐free field‐effect behavior in NW‐FETs demonstrated leakage‐free liquid‐gate operation demonstrated pH sensing with nanowires  surface functionalization for (a) passivated nanowires (b) glycoprotein‐binding  nanowires Signal and signal‐to‐noise: noise measurements and modelling of sensitivity systematic evaluation of physical parameters, e.g. width, length, doping, ion  concentration, length of molecules etc. onoing system concepts 36
  37. 37. Thanks to....Uni Basel Uni Basel physics pharma Christian Oren Wangyang Fu Mathias Wipf Michel Calame Alexey Tarasov Beat Ernst Arjan Odedra Schönenberger KnopfmacherEPFL PSI Mohammad Birgit Vitaliy Christian Adrian Ionescu Sara Rigante Jens Gobrecht Kristine Bedner Najmzadeh Päivänranta Guzenko DavidETHZ D-BSSE Bernd Robert Andreas Janos Vörös Paolo Livi Yihui Chen Dielacher MacKenzie HierlemannFHNW Sensirion Uwe Pieles Jolanta Kurz Matthias Sreiff 37

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