Scanning ion conductance microscopy (SICM) is a scanning probe microscopy (SPM) technique that is well-suited for topographic and conductance mapping of biological and physical interfaces. In SICM, a potential difference applied between an electrode inside an electrolyte-filled nanopipette and a second electrode outside the nanopipette results in a steady-state ion current. This ion current flowing through the pipette is strongly influenced by the relative position between the SICM probe and a sample of interest, and provides a feedback signal to precisely control the position of the probe. These position-dependent changes in conductivity enable SICM to measure both nanoscale features and physical properties of the sample under study. The Baker Group utilizes SICM to study the fundamental properties of ion transport through pores.
We have modified the conventional two-electrode SICM to study ion transport and have developed three-/four-electrode SICM and the five-electrode potentiometric SICM (P-SICM). P-SICM is a hybrid voltage scanning mode of SICM for recording transmembrane ionic conductance at specific nanostructures of synthetic and biological interfaces. With this technique, paracellular conductance through tight junctions – a subcellular structure that has been difficult to interrogate previously – has been realized. P-SICM utilizes a dual-barrel pipette to differentiate paracellular from transcellular transport processes with nanoscale spatial resolution. The unique combination of voltage scanning and topographic imaging enables P-SICM to capture paracellular conductance within a nominal radius of several hundred nm.
Novel probes for SICM: gains in information
Ion Channel Probes-SICM
Recently we have described an ion channel probes (ICPs), which consist of multiple ion channels reconstituted into lipid bilayers suspended across the opening of perflourinated glass micropipets, as SICM probes. ICPs show distance-dependent ion current and can be used in SICM imaging. The selectivity and small size of ion channels make ICPs promising for incorporating chemical information to SICM.
Coupling with Scanning Electrochemical Microscopy (SECM)
Scanning Electrochemical Microscopy (SECM) is a type of scanning probe microscopy that uses faradaic current (i.e. current produced by electron transfer in a redox reaction) to obtain information about a system under study. The probes utilized are termed ultramicroelectrodes because their diameters typically range from 10s of nm to 10s of µm. SECM provides chemical information in image collection, as redox species may be targeted by biasing the probe to a particular potential.
Fabrication of different ultramicroelectrodes from nanopipettes incorporates chemical specificity from SECM together with high resolution imaging offered by the robust feedback system of SICM. Recent work in the Baker Group has focused on the fabrication of SICM-SECM electrodes. Baker group members have used pyrolyzed parylene C, and parylene (conductive and insulative materials, respectively), as well as a focused-ion beam, to fabricate multifunctional electrodes for SECM and SICM imaging. We have also developed a strategy for electrode fabrication which utilizes gold and parylene coating to simultaneously perform topographic, conductance and electrochemical imaging.
a) SEM micrograph of nanopipette-electrode with a clear distinction between the Au electrode (right), quartz (left) and parylene C insulation (top). b) SEM micrograph of a nanopipet tip with PANi ﬁlm on the surface of the AuE post electropolymerization. c) SEM micrograph of a carbon ring/nanopore electrode with an outer radius of 485 nm, inner radius of 295 nm, and nanopore dimensions of 440 nm (diameter).
Commercial SICM systems:
Baker group publications associated with this research topic:
Weber, A,E.; Shi, W.; Baker, L.A. Electrochemical Applications of Scanning Ion Conductance Microscopy. In Electroanalytical Chemistry; Bard, A.J., Zoski, C. Eds.; 2014, accepted.
Weber, A,E.; Baker, L.A. Experimental Studies of Resolution in Scanning Ion Conductance Microscopy, J. Electrochem. Soc., 2014, 161, H924-H929. (http://jes.ecsdl.org/content/161/14/H924 )
Zhou, Y.; Bright, L.; Shi, W.; Aspinwall, C.A.; Baker, L.A. Ion Channel Probes for Scanning Ion Conductance Microscopy, Langmuir, 2014, accepted. (http://doi/abs/10.1021/la504097f)
Zhou, L.; Zhou, Y.; Baker, L.A. Measuring Ions with Scanning Ion Conductance Microscopy, ECS Interface, 2014, 2, 51-56. (http://www.electrochem.org/dl/interface/sum/sum14/if_sum14.htm)
Zhou, Y.; Chen, C.C.; Weber, A.E.; Zhou, L.; Baker, L.A. Potentiometric Scanning Ion Conductance Microscopy, Langmuir, 2014, 30, 5669–5675. (http://dx.doi.org/10.1021/la500911w)
Sa, N.; Lan, W.; Shi, W.; Baker, L.A. Rectification of Ion Current in Nanopipettes by External Substrates, ACS Nano, 2013, 7, 11272–11282. (http://dx.doi.org/10.1021/nn4050485)
Thakar, R.; Weber, A.E.; Morris, C.A.; Baker, L. A. Multifunctional Carbon Nanoelectrodes Fabricated by Focused Ion Beam Milling, Analyst, 2013, accepted. (http://dx.doi.org/10.1039/c3an01216f).
Zhou, Y.; Chen, C.C.; Weber, A.; Zhou, L.; Baker, L. A.; Hou, J. Potentiometric-Scanning Ion Conductance Microscopy for Measurement at Tight Junctions, Tissue Barriers, 2013, 1, e2558s. (https://www.landesbioscience.com/journals/tissuebarriers/article/25585/).
Morris, C.A.; Chen, C.; Ito, T.; Baker, L. A. Local pH Measurement with Scanning Ion Conductance Microscopy. J. Electrochem. Soc., 2013, 160, H430-H435. (http://dx.doi.org/10.1149/2.028308jes).
Chen, C.; Zhou, Y.; Morris, C.A.; Hou, J.; Baker, L.A. Scanning ion conductance microscopy measurement of paracellular conductance in tight junctions. Anal. Chem., 2013, 85, 3621-3628. (http://dx.doi.org/10.1021/ac303441n).
Chen, C.; Zhou, Y.; Baker, L.A. Scanning Ion Conductance Microscopy. Annu. Rev. Anal. Chem., 2012, 5, 207-228. (http://dx.doi.org/10.1146/annurev-anchem-062011-143203).
Zhou, Y.; Chen, C.; Baker, L. A., Heterogeneity of Multiple-pore Membranes Investigated with Ion Conductance Microscopy. Anal. Chem., 2012, 84, 3003-3009. (http://dx.doi.org/10.1021/ac300257q).
Morris, C.A.; Chen, C.; Baker, L.A. Transport of Redox Probes through Single Pores Measured by Scanning Electrochemical-Scanning Ion Conductance Microscopy (SECM-SICM). Analyst, 2012, 137, 2933-2938. (http:// dx.doi.org/10.1039/C2AN16178H).
Chen, C.; Zhou, Y.; Baker, L.A. Single nanopore investigations with ion conductance microscopy. ACS Nano, 2011, 5, 8404-8411 (http://dx.doi.org/10.1021/nn203205s).
Sa, N.; Baker, L.A. Rectification of nanopores at surfaces. J. Am. Chem. Soc., 2011, 133, 10398-10401. (http://dx.doi.org/10.1021/ja203883q)
Morton, K. C.; Morris, C. A.; Derylo, M. A.; Thakar, R.; Baker, L. A. Carbon electrode fabrication from pyrolyzed parylene c. Anal. Chem., 2011, 83, 5447-5452. (http://dx.doi.org/10.1021/ac200885w).
Chen, C., Baker, L.A. Effects of pipette modulation and imaging distances on ion currents measured with Scanning Ion Conductance Microscopy (SICM). Analyst, 2011, 1, 90-97. (http://dx.doi.org/10.1039/C0AN00604A)
Morris, C.; Friedman, A. K.; Baker, L. A. Applications of Nanopipettes in the Analytical Sciences. Analyst, 2010, 135, 2190-2202. (http://dx.doi.org/10.1039/c0an00156b)
Chen, C.; Derylo, M.; Baker, L. A. Measurement of Ion Currents through Porous Membranes with Scanning Ion Conductance Microscopy. Anal. Chem., 2009, 81, 4742-4751. (http://dx.doi.org/10.1021/ac900065p)