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Protocol

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Materials

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Bioengineering

Fabrication of Carbon Nanotube High-Frequency Nanoelectronic Biosensor for Sensing in High Ionic Strength Solutions

Published: July 22nd, 2013

DOI:

10.3791/50438

1Department of Electrical Engineering and Computer Science, University of Michigan - Ann Arbor

We describe the device fabrication and measurement protocol for carbon nanotube based high frequency biosensors. The high frequency sensing technique mitigates the fundamental ionic (Debye) screening effect and allows nanotube biosensor to be operated in high ionic strength solutions where conventional electronic biosensors fail. Our technology provides a unique platform for point-of-care (POC) electronic biosensors operating in physiologically relevant conditions.

The unique electronic properties and high surface-to-volume ratios of single-walled carbon nanotubes (SWNT) and semiconductor nanowires (NW) 1-4 make them good candidates for high sensitivity biosensors. When a charged molecule binds to such a sensor surface, it alters the carrier density5 in the sensor, resulting in changes in its DC conductance. However, in an ionic solution a charged surface also attracts counter-ions from the solution, forming an electrical double layer (EDL). This EDL effectively screens off the charge, and in physiologically relevant conditions ~100 millimolar (mM), the characteristic charge screening length (Debye length) is less than a nanometer (nm). Thus, in high ionic strength solutions, charge based (DC) detection is fundamentally impeded6-8.

We overcome charge screening effects by detecting molecular dipoles rather than charges at high frequency, by operating carbon nanotube field effect transistors as high frequency mixers9-11. At high frequencies, the AC drive force can no longer overcome the solution drag and the ions in solution do not have sufficient time to form the EDL. Further, frequency mixing technique allows us to operate at frequencies high enough to overcome ionic screening, and yet detect the sensing signals at lower frequencies11-12. Also, the high transconductance of SWNT transistors provides an internal gain for the sensing signal, which obviates the need for external signal amplifier.

Here, we describe the protocol to (a) fabricate SWNT transistors, (b) functionalize biomolecules to the nanotube13, (c) design and stamp a poly-dimethylsiloxane (PDMS) micro-fluidic chamber14 onto the device, and (d) carry out high frequency sensing in different ionic strength solutions11.

When a charged molecule binds to a SWNT or NW electronic sensor, it can either donate/accept electrons or act as a local electrostatic gate. In either case, the bound molecule can alter the charge density in the SWNT or NW channel, leading to a change in the measured DC conductance of the sensor. A large variety of molecules15-20 have been successfully detected by studying DC characteristics of the nanosensors during such binding events. Even though charge-detection based sensing mechanism has many advantages including label-free detection21, femto-molar sensitivity22, and electronic read out capability15; it is effective on....

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1. Catalyst Patterning for SWNT Growth

  1. Begin with a silicon wafer with a low pressure chemical vapor deposition (CVD) grown 500 nm Si3N4/ 500 nm SiO2 film on top.
  2. Spin coat a layer of photoresist (PR) at 500 rpm for 5 sec and then 4,000 rpm for 40 sec.
  3. Bake the wafer at 115 °C for 90 sec.
  4. Use a photomask with rectangular pits for catalysts (Figure 1) and expose the wafer in UV (365 nm) irradiance of 300 mJ/cm2 for 0.......

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A scanning electron microscope image of SWNT transistor with a suspended top gate is shown in Figure 7a. The gate dimensions are critical for suspension25. The current design dimensions are (length x width x thickness = 25 μm x 1 μm x 100 nm). The gate electrode consists of 50 nm Cr/50 nm Au; a thick chrome layer adds more strength to suspended structure. The suspended structure is confirmed by absence of leakage current between top gate and drain (Figure 7b).

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The growth of carbon nanotubes depends not only on furnace conditions but also substrate cleanliness. The optimal gas flow rate, temperature and pressure for growth have to carefully calibrated and once fixed they are more or less stable. Even with these conditions being met, we found that growth depends on the patterned catalyst area, amount of catalyst and substrate cleanliness. Hence, we incorporated multiple catalyst pit sizes to account for the variability in growth. A one hour high temperature anneal step helped re.......

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We thank Prof. Paul McEuen at Cornell University for early discussion. The work is supported by the start-up fund provide by the University of Michigan and the National Science Foundation Scalable Nanomanufacturing Program (DMR-1120187). This work used the Lurie Nanofabrication Facility at University of Michigan, a member of the National Nanotechnology Infrastructure Network funded by the National Science Foundation.

....

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Name Company Catalog Number Comments
      REAGENTS
      Reagents which were provided within Lurie Nanofabrication Facility (University of Michigan) are marked as LNF in the catalogue column. Chemicals which require protective equipment (gloves, safety goggles, face mask, apron) and/or fume hood are denoted with PPE in comments section.
Silicon wafers (P-type, <100>, 500-550 μm thick) Silicon Valley Microelectronics    
SPR 220 3.0 Dow (Rohm and Haas) Megaposit SPR PPE
AZ 300MIF AZ Electronic Material Corporation   PPE
Acetone J T Baker 9005-05 PPE
Isopropanol (IPA) J T Baker 9079-05  
Buffered Hydrofluoric Acid Transene   PPE
1-Pyrene Butanoic Acid, succinimidyl ester Molecular Probes P130 PPE
Biotin PEO Amine Thermo Scientific EZ- Link PEG2 Biotin, # 21346 PPE
Streptavidin Invitrogen S 888 PPE
Dimethylformamide MP Biomedicals 0219514791 PPE
Polydimethylsiloxane Elastomer Base and Curing Agent Dow Corning Sylgard 184 Elastomer Kit PPE
SU-8 2015 Microchem Y111064 PPE
SU-8 Developer Microchem Y020100 PPE
Silanizing agent Sigma Aldrich 452807 PPE
Hydrogen Purity Plus LNF  
Ethylene Purity Plus LNF  
Argon Purity Plus LNF  
Phosphate Buffer Saline System Sigma Aldrich PBS1  
      EQUIPMENT
      Equipment provided by Lurie Nanofabrication Facility (University of Michigan) is denoted as LNF in Catalogue column.
GCA 200 Autostepper GCA LNF  
Low Pressure Chemical Vapor Deposition Tool Tempress LNF  
e-beam Evaporator Enerjet LNF  
CNT growth Furnace First Nano Easy Tube 3000 (LNF)  
Photomasks Nanofilm LNF  
Petri dish (150mm)   LNF  
Desiccator Bel-Art F420100000  
Biopsy Punch Ted Pella 15071/78  
Scalpel Ted Pella 548  
Polyethylene Tubing PE-50 VWR 20903-414  
Syringe Pump New Era Pump Systems NE-1000  
Syringe Fisher Scientific BD Safety-Lok Syringes  
Syringe Needles Fisher Scientific 14-821-13A  
DAQ card National Instruments 779111-01  
GPIB connector National Instruments 778032-51  
Lock-in Amplifier Stanford Research Systems SR 830  
Frequency Generator HP Agilent 8648B, 9kHz -2GHz  
Bias Tee Picosecond 5575A-104  
Current Preamplifier DL Instruments, LLC DL 1211  
BNC cables Allied Electronics 665-xxxx  
SMA cables Sentro Tech Corp SCF65141  

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