title: Fabrication of carbon nanotube high-frequency nanoelectronic biosensor for sensing in high ionic strength solutions.
abstract: The unique electronic properties and high surface-to-volume ratios of single-walled carbon nanotubes (SWNT) and semiconductor nanowires (NW) make them good candidates for high sensitivity biosensors. When a charged molecule binds to such a sensor surface, it alters the carrier density 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 impeded. 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 mixers. 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 frequencies. 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 nanotube, (c) design and stamp a poly-dimethylsiloxane (PDMS) micro-fluidic chamber onto the device, and (d) carry out high frequency sensing in different ionic strength solutions.
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Michigan-Ann Arbor, Ann Arbor, Michigan, USA.
authors.forename: Girish S
authors.initials: GS
authors.lastname: Kulkarni
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004867:Equipment Design; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009994:Osmolar Concentration; D019095:Point-of-Care Systems; D012996:Solutions / Q000737:chemistry
chemical_list: D004129:Dimethylpolysiloxanes; D037742:Nanotubes, Carbon; D012996:Solutions; C013830:baysilon
references.citation: Nano Lett. 2011 Sep 14;11(9):3739-43
references.pmid: 21806018
references.citation: Science. 2000 Jan 28;287(5453):622-5
references.pmid: 10649989
references.citation: Nano Lett. 2012 Oct 10;12(10):5245-54
references.pmid: 22963381
references.citation: Nano Lett. 2008 Apr;8(4):1066-70
references.pmid: 18311939
references.citation: Science. 2005 Mar 25;307(5717):1942-5
references.pmid: 15790850
references.citation: Nano Lett. 2012 Feb 8;12(2):719-23
references.pmid: 22214376
references.citation: Anal Chem. 1998 Dec 1;70(23):4974-84
references.pmid: 21644679
references.citation: Anal Chem. 2006 Jul 1;78(13):4260-9
references.pmid: 16856252
references.citation: Nat Biotechnol. 2005 Oct;23(10):1294-301
references.pmid: 16170313
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):921-6
references.pmid: 16418278
references.citation: J Am Chem Soc. 2001 Apr 25;123(16):3838-9
references.pmid: 11457124
references.citation: Nature. 2007 Feb 1;445(7127):519-22
references.pmid: 17268465
references.citation: Nature. 2001 Jan 4;409(6816):66-9
references.pmid: 11343112
references.citation: Nano Lett. 2007 Nov;7(11):3405-9
references.pmid: 17914853
references.citation: Nano Lett. 2012 Sep 12;12(9):4748-56
references.pmid: 22852557
references.citation: Nano Lett. 2008 Feb;8(2):591-5
references.pmid: 18162002