Scanning Probe Microscopy - ACS Publications - American Chemical

Anal. Chem. 2002, 74, 2851-2862

Scanning Probe Microscopy Mark A. Poggi,† Lawrence A. Bottomley,*,† and Peter T. Lillehei‡

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, and Advanced Materials and Processing Branch, NASA Langley Research Center, Hampton, Virginia 23681-2199 Review Contents Instrumental Innovations Probes Hardware Improvements New Techniques Imaging Applications Scanning Tunneling Microscopy (STM) Scanning Electrochemical Microscopy (SECM) Magnetic Imaging Nanofabrication Biology Sensors Force Spectroscopy Characterization of Carbon Nanotubes Literature Cited

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Scanning probe microscopy (SPM) encompasses a family of techniques that measure surface topography and surface properties on the atomic scale. The number of papers devoted to technical advances and applications of SPM continues to rise. Contributing factors to this increasing interest include the desire to manipulate matter on the atomic scale and the availability of high-quality commercial instruments. The format of this review, covering papers published during the period January 1, 2000 through December 31, 2001, is similar to that published two years ago. More than 11 000 citations were found using the SciFinder search engine that pertained to or applied scanning probe methods. The intent of this review is to highlight the most important contributions to the field published within the aforementioned period. Our selections illustrate only some of the research avenues currently being explored with SPM and are, without doubt, subjective. INSTRUMENTAL INNOVATIONS Probes. Recent progress has been reported in the fabrication and use of ultrasmall cantilevers. Chand et al. (1) fabricated gold cantilevers with integrated silicon tips that were 13-40 µm long. The shortest of these resonated at 0.5 MHz with a Q factor of 100. Residual stress in the gold was relieved using rapid thermal annealing and thereby reducing the extent of cantilever bending. Hosaka and co-workers (2) fabricated cantilevers that were 7-20 µm long having a maximum resonant frequency of 6.6 MHz. They reported the acquisition of images at scanning rates 4 orders of magnitude faster than normal scanning rates. Yang and co-workers (3) fabricated ultrathin cantilevers from SIMOX wafers. These cantilevers are theoretically capable of detecting forces as small as 1.4 × 10-16 N in the first resonance † ‡

Georgia Institute of Technology. NASA Langley Research Center.

10.1021/ac025695w CCC: $22.00 Published on Web 05/11/2002

© 2002 American Chemical Society

mode. Even smaller minimum detectable forces are achievable when using higher resonance modes. McCarthy and colleagues (4) have demonstrated the utility of focused-ion beam (FIB) milling in creating thin cantilevers (below 1 µm). Fabricating cantilevers that possess integrated instrumentation on chip will significantly reduce the size of equipment required for scanning probe experiments. Heisig and co-workers (5) have designed a GaAs cantilever probe with an integrated vertical cavity surface emitting laser above the cantilever tip. This integrated design simplified the optical components of the SFM. Lee et al. (6) designed a single cantilever probe consisting of a small torsional resonator incorporated onto the end of the cantilever for improved force detection/actuation. The cantilever’s fundamental resonance frequency was 49 kHz. The resonator was coated with a thin film of Pt-Cr and driven with an external magnetic field at 3 MHz. This approach reduced the minimum detectable force by 2 orders of magnitude relative to a conventional cantilever and substantially improved the signal-to-noise ratio necessary for ultrafast scanning. Kawakatsu and co-workers (7) have designed uniquely shaped probes that resonate in the gigahertz range. The oscillator has a tetrahedral or conical tip between 100 and 1000 nm in diameter supported by an elastic neck. Experimentally induced tip-crash generally requires manual replacement of the probe. Genolet and co-workers (8) have designed multiple, single-lever probes arranged in a cassette format. The cassette consists of a one-dimensional array of photoplastic cantilevers with integrated tips. The first cantilever is used for imaging while the others are available if the first one becomes degraded. A worn-out cantilever can be replaced with a fresh one by only small positional adjustments and without any changes in the operating conditions. Hybrid scanning force and near-field scanning optical microscopy (NSOM) probes provide optical and topographical information about the underlying substrate. Dual-functioning probes have been made by various micromachining methods (9, 10). Recent emphasis has been placed on devising methods that create smaller and more reproducible aperture geometries. Focused-ion beam (FIB) milling is a high-precision technique that can be used to create unique and reproducible silicon structures. Although a FIB milling tool is expensive and possesses low sample throughput, it is currently the best way to fabricate hybrid probes. Lehrer et al. (11) utilized FIB milling to create a reproducible aperture of less than 50 nm at the tip of a conventional SFM cantilever. Genolet et al. (12) produced a hybrid probe that consists of a micromachined polymeric tip with an aperture at the apex that is attached to an optical fiber. This probe takes advantage of the reproducibility of batch fabrication processes for micromachined Analytical Chemistry, Vol. 74, No. 12, June 15, 2002 2851

tips and the well-characterized light-guiding characteristics of optical fibers. Extremely small probes have been fabricated without any postprocessing steps. Topographical and optical imaging with the probe demonstrates the great potential of the photoplastic probe for NSOM applications. Carbon nanotubes have the potential to be ideal SPM probes due to their unique properties including small diameter, high aspect ratio, large Young’s modulus, and mechanical robustness. The nanotubes can also be chemically functionalized leading to advanced chemical and biological mapping studies. The use of nanotubes as probes for SPM has gained momentum in the last two years. Hafner et al. (13), pioneers in the field of using carbon nanotubes as SFM probes, wrote an excellent review of their use in structural and functional imaging. This review covers the topics of the fabrication, structural and mechanical properties, characterization of the tip, resolution, applications, functional imaging, and force spectroscopy. Nanotube tips can be fabricated in a variety of ways. Cheung et al.(14) have grown single-walled nanotubes (SWNTs) directly on the tip via a surface growth chemical vapor deposition method. The tips can also be used in SWNT lithography, where SWNTs are patterned on a substrate by peeling them off an SFM tip. Other fabrication techniques include picking up vertically aligned SWNT from a silicon surface (15) and using an arc discharge to transfer multiwalled nanotubes (MWNTs) to the SFM tip (16). Nanotube probes are mechanically robust, maintain their lateral resolution, and are readily functionalized (13, 17, 18). Akita et al. (19) have fabricated a nanotweezer consisting of MWNT ∼2.5 mm long separated by 780 nm. A dc voltage applied to two electrodes causes the nanotubes to be electrostatically attracted to each other, closing the nanotweezers. Nanotube tips are sharp yet “gentle”, providing images of biomolecules and bioassemblies with resolution comparable to cryogenic electron microscopy. Some of the biological systems examined include the following: RecA-DNA (20), mono- and polynucleosomes (21), IgG (22), IgM (13), GroES (22), and amyloid-β fibrils (13). Woolley et al. (23) developed a method for multiplexed detection of polymorphic sites and direct determination of haplotypes in DNA fragments. With this technique, it is possible to detect single-nucleotide polymorphisms in sequences up to 10 000 bases. Hardware Improvements. Schaffer et al. (24) have implemented a new detector for SFM. The optical power from the beam is distributed across a photodetector array, splitting it into multiple channels. An adjustable gain factor is dynamically set to weigh the contribution from each channel. A factor of 5 improvement in signal-to-noise ratio over the conventional segmented detector was obtained. Nishino and co-workers (25) developed a tensile loading stage that facilitated the observation of polymer films under stress. Strain was determined from measurements of the changes in distance between image features on a poly(ethylene terephthalate) film surface as a function of tensile load. Strain was evaluated both parallel and perpendicular to the tensile load direction. The microscopic stress-strain relationship determined by SFM coincided with that determined in a conventional macroscopic mode, suggesting that deformation of the film is an affine process. Progress in cantilever arrays has been critically evaluated by Vettiger and co-workers (26). Recent emphasis has focused on 2852

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reducing the size and increasing the number of actuators in the array. Cantilever arrays have been proposed as an alternative highdensity data storage device. Cross and co-workers (30) have carried out theoretical and experimental treatments on the reading/writing capabilities of polymer indentations carried out with a thermomechanically actuated SFM. King and co-workers (27) continued their evaluation of a resistively heated cantilever as a thermomechanical data storage device. Their technique uses the cantilever to write/read/erase/rewrite bits of data into a thin polymer layer on a silicon surface. Heat conduction governs the ultimate writing and reading capabilities of the device. They measured and simulated transient thermal and electrical behavior in a resistively heated cantilever and concluded that reduction in cantilever dimensions and tip height should improve the speed and sensitivity of the writing step. Chow et al. (28) improved upon previous arrays by incorporating through-wafer interconnects enabling more complicated and compact arrays to be fabricated. Integration of the cantilevers, tips, and interconnects will enable operation of a high-dimension probe array over large areas. Despont et al. (29) set out to improve the data reading and writing characteristics of cantilever arrays. They fabricated a 32 × 32 cantilever array with integrated Schottky diodes in series with each cantilever. This led to a large reduction in cross talk between actuators. In addition to their application in data storage, cantilever arrays facilitate faster imaging over large substrate domains. Sulchek and co-workers (31) created an instrument with parallel readout from an array of five cantilevers using an interferometric detection scheme. Each cantilever contained a phase-sensitive diffraction grating consisting of a reference and movable set of interdigitated fingers. As a force is applied to the tip, the movable set is displaced and the intensity of the diffracted orders is altered. The order intensity from each cantilever is measured with a custom array of silicon photodiodes with integrated complementary metal oxide-semiconductor amplifiers. Their interdigital method for cantilever array readout is scalable, provides angstrom resolution, and is potentially simpler to implement than other methods. Akiyama et al. (32) successfully used a 2 × 1 array of active and self-detecting cantilevers to acquire two images taken in parallel. The cantilevers possess an integrated deflection sensor based on a stress-sensing metal oxide-semiconductor transistor and amplifiers for signal readout. The number of electrical interconnects were significantly reduced by routing electric signals directly on the chip. Constant-height mode, tapping mode, and force mode images were obtained with this array. The creation of automated instruments that can acquire images without human involvement was a focus for research on improving SPM instrumentation. For example, Akiyama and co-workers (33) have built a stand-alone instrument for conducting soil and dust analyses on Mars. Their instrument is capable of self-engaging the cantilever on a substrate and frequency modulation measurements. Barth and co-workers (34) described an array-based SFM designed for imaging interplanetary particles onboard the ESA Midas/Rosetta space mission vehicle. Another focus involved increasing scanning speed. Sulchek and co-workers (35) have achieved high-speed SFM imaging in solution. Their technique used a ZnO self-actuating cantilever and achieved an imaging bandwidth 100 times faster than typical

SFMs. Ando et al. (36) designed a SFM capable of obtaining 100 × 100 pixel images of biological media within 80 ms. The apparatus consisted of a newly designed sample scanning system free of resonant vibrations up to 60 kHz and short, flexible cantilevers with high resonance frequencies. Images detailing the movement of myosin on mica under buffer solution were acquired with this instrument. Several groups have investigated improvements in apparent cantilever Q factor using acoustic, radiation pressure, and magnetic actuation to improve force sensitivity (37-39). Methods for improving Q factors have immediate application in imaging, dynamic force spectroscopy measurements, and microcantileverbased sensors (40, 41). New methods for determining cantilever spring constants under fluid have been developed. Maeda and Senden (42) presented a semiempirical relationship between the deflection of a cantilever under a point load and the same cantilever under laminar flow. This relationship enables in situ determinations of cantilever force constants and demonstrates that the hydrodynamic contribution to cantilever deflection is linear with speed, independent of tip size and position, and scale invariant. Craig and Neto (43) have extended this work to include attachment of colloidal particles on the tip. Degertekin et al. (38) have devised a novel method to actuate SFM cantilevers in fluids via focused acoustic waves. This technique can be used to measure the spring constant and resonance frequency of various SFM probes. The frequency response is determined by the bandwidth of an acoustic transducer/Fresnel lens system. Cain and co-workers (44) developed a method of force calibration for a lateral force microscope. By using spheres of different radii, the effects of contact stiffness can be isolated and an absolute force calibration achieved in terms of measured beam deflections. The method does not rely on any particular model of contact mechanics and extends the capability of lateral force microscopy (LFM) to quantify frictional forces between arbitrary materials. New Techniques. Krotil et al. (45) have created a new scanning force technique in which a low-frequency vertical modulation is combined with a second high-frequency lateral modulation as the tip translates across the surface of the substrate. This enables topographical mapping of the surface simultaneously with quantitative mapping of adhesive, static, and dynamic frictional forces (46). Similarly, Syed Asif and co-workers (47) have designed a hybrid nanoindenting instrument that combines a depth-sensing nanoindenter with scanning-probe imaging capabilities. This instrument is capable of measuring the damping coefficient and loss modulus of a substrate while generating a topographical picture of the regions with different mechanical properties. Takano et al. (48) have shown that electric force microscopy (EFM) can be used to map compositional differences in organic monolayers buried under a thick polymeric film. A mixed underlayer composed of methyl- and hydroxyl-terminated alkanethiols was patterned onto a gold surface using microcontact printing. EFM imaging exhibits sufficient contrast to function as a mapping methodology for buried functional groups. Anderson has integrated vibrational spectroscopy with an SFM (49, 50). In the first report, a cantilever was used to spatially

enhance a Raman signal via surface-enhanced Raman scattering. In the second report, Anderson used the cantilever as an IR detector and a surface separation device for spectroscopic analyses of substrates. These combined vibrational spectroscopy/probe microscopy approaches enable acquisition of high-content spectra that identifies the chemical composition of image features. With advances in device miniaturization, it is becoming increasingly difficult to test their electrical properties, especially resistance. The probes commonly used in SFM-based electrical characterizations are either silicon probes with conductive coatings or silicon probes with integrated tips (51). Scanning spreading resistance microscopy (SSRM) is a technique commonly used for characterizing semiconductor devices. Hantschel and co-workers (52) designed diamond-tipped probes integrated onto a silicon cantilever. This probe increases the dynamic range of SSRM by an order of magnitude. Boggild and co-workers (53) fabricated a nanoscale four-point probe device for high spatial resolution conductivity measurements on surfaces and thin films. Scanning thermal microscopy maps spatial variations in temperature, thermal conductivity, or thermal diffusivity on a surface. Recent efforts have focused on improving spatial resolution and probe response time through reduction in probe geometry (5456). Li and co-workers (57) fabricated thermal probes in which a thin thermocouple wire is imbedded in a polyimide cantilever. They found that the thermal sensitivity of polymeric probes could be up to 10 times greater than silicon-based probes of similar dimension. Wold (58), Cui (59), and their colleagues have independently shown that conducting probe-SFM is a reliable method for fundamental studies of electron transfer through small numbers of molecules. The junction resistance of alkanethiol molecules increased exponentially with chain length and decreased with increasing load. Conducting probe-SFM measurements open opportunities for exploring electron transfer as a function of molecular deformation. Topinka and co-workers (60) successfully imaged electron flow from two quantum point contacts. The electron flow is imaged by scanning a negatively charged, conductive SFM tip above the surface of the device while measuring the position-dependent conductance. IMAGING APPLICATIONS Scanning Tunneling Microscopy (STM). The focus of STM imaging studies for many years has centered on high-resolution characterizations of single-crystal conductor or semiconductor surfaces. Bobrov and co-workers (61) have demonstrated that STM can be used to image insulators. Using a resonant electron injection mode, they imaged a diamond surface and probed its electronic properties at the atomic scale. Their results reveal striking electronic features in high-purity diamond single crystals including the existence of one-dimensional, fully delocalized electronic states and a very long diffusion length for conduction band electrons. This imaging mode shows promise in characterizing other insulating substrates. Recent emphasis has shifted toward the structure and dynamics of superlattice assemblies. For example, De Feyter et al. (62) studied the effect of chirality on monolayer formation. Highresolution STM images confirm that, for all polymorphs, molecular chirality is transferred to the two-dimensional adlayer structure Analytical Chemistry, Vol. 74, No. 12, June 15, 2002

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in an enantiospecific way. This enantiospecificity is attributed to adsorbate-substrate interactions. Ohira and co-workers (63) observed potential-induced assembly of β-cyclodextrin molecules into nanotube-like structures. By switching the potential versus the SCE, disordered cyclodextrin molecules translated into an ordered arrangement on the gold electrode surface. Yokoyanna and co-workers (64) successfully created surface-supported supramolecular structures by tuning the noncovalent interactions between individually adsorbed porphyrin molecules. Using lowtemperature STM, they found that substituted porphyrin molecules sublimed onto a gold surface form monomeric, trimeric, tetrameric, or extended wirelike structures, depending upon the number and placement of cyanophenyl substituents. STM has been an invaluable tool for manipulating matter on the atomic scale since Eigler first demonstrated that atoms could be arranged on a surface with a tunneling tip. Recent focus has centered on manipulating molecules on surfaces. Gorman and coworkers (65) presented a STM-based lithographic method for selectively removing and replacing thiolates in a self-assembled monolayer. This method is distinguishable from other lithographic replacement processes on SAMs in that a nonpolar solution and an uncoated tip can be employed. The resolution of features written with this process is approximately 10-15 nm. A similar method has been investigated for patterning proteins (66). Shigekawa et al. (67) demonstrated that the R-cyclodextrin molecules in a polyrotaxane can be shuttled with a STM probe. Hla and co-workers (68) took advantage of STM’s ability of manipulate single molecules and induced all of the elementary steps of a chemical reaction between individual molecules. Specifically, they separated iodine from iodobenzene using tunneling electrons, brought together two resultant phenyls by lateral manipulation, and formed a biphenyl molecule mediated by excitation with tunneling electrons (69, 70). This report constitutes an important next step in the in situ assembly of individual molecules out of simple, atomic scale building blocks. Okawa and co-workers (71) have created polymer nanowires on a conductive surface. This process was initiated, stimulated, and terminated by a STM tip. The electronic properties of metallic nanoclusters on semiconductor surfaces is important in designing nanoelectronic devices (72). Gurevich and co-workers (73) took advantage of the high spatial resolution of STM in performing electrical tests on these nanostructures. A twin-tipped STM probe was used to make electrical contact with the nanocluster. The tunneling bias voltage determined the voltage drop across the source (one tip) and the drain (the substrate). The second tip in contact with the nanocluster enabled adjustment of the gate voltage. Gittins and co-workers (74) attached metal nanoparticles to electrode surfaces using organic linker molecules containing redox centers. Scanning tunneling spectroscopy was used to probe electron transport through this assembly. It was shown that the redox state of the linker controlled electron transport between the nanoparticles and the underlying electrode. The ability to electronically contact metal nanoparticles via redox-active molecules, and to alter their tunneling properties by charge injection into them, forms the basis for using nanoclusters as electronic switches. Scanning Electrochemical Microscopy (SECM). SECM is a scanned probe technique that depends on nanoscale electro2854

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chemistry. Through the use of high-resolution positioning of ultramicroelectrodes, spatially resolved electrochemical reactions are performed. Shuttling of an electroactive species between the ultramicroelectrode and the substrate provides topographical information. From a microscopy standpoint, spatial resolution in SECM is much poorer than that obtained with SFM. Further reduction in the size of electrodes is unlikely to significantly improve this situation since the feedback mechanism relies on mass transport of an electroactive species between two surfaces (tip and substrate). This imaging mode, however, enables one to distinguish between conductive and insulating features on the substrate. In this context, the coupling of SECM with SFM for high spatial resolution imaging of surfaces with simultaneous electrochemical measurements is noteworthy. Dual-functioning probes were fabricated by coating a flattened and etched Pt microwire with an insulator. The flattened portion of the probe provides a flexible cantilever while the coating insulates the probe such that only the tip end (electrode) is exposed to the solution (75). Alternatively, a dual-functioning probe can be fabricated by FIB milling of metal-coated cantilever tips creating an electroactive area at a predefined region above the probe (76). With these probes, topography is tracked by cantilever deflection while the conductivity of the substrate is determined electrochemically. Mirkin and Horrocks (77) provided a very thorough review of all the aspects of SECM, from theory to application. The review focuses on instrumentation, basic principals/theory, and selected applications. Recent advances in SECM are described, and the current state of the art in imaging topography and chemical reactivity are highlighted. Applications include investigations of thin films, immobilized enzymes, liquid/liquid and liquid/gas interfaces, single-molecule electrochemistry, and imaging. Another review by Wittstock (78) critically examines the use of SECM in the modification and characterization of patterned enzymatically active surfaces. Discussions of the challenges involved and the potential solutions from ongoing research are highlighted. Lee, Amemiya, and Bard (79) expanded on their previous development of SECM theory in their treatment of the theory and characterization of ring electrodes. Planar disks are the most frequently used electrodes in SECM. However, other geometries are important as the size of the tip is reduced. Ring electrodes can be fabricated by depositing a metal on the shaft of an optical fiber. This type of arrangement allows for simultaneous NSOM and SECM. Their report is the first study of the theory of SECM response with a ring-shaped tip allowing for a detailed understanding of the electrochemical processes. Biological systems investigated by SECM during this review period include imaging the distribution and permeability of methyl viologen (80) and oxygen (81) in cartilage. Liu et al. (82) probed the redox potential of living cells and discovered significant differences between metastatic and nonmetastatic cells. Magnetic Imaging. In this section, pertinent literature on scanning probe techniques that detect magnetic properties of samples is reviewed. Magnetic resonance force microscopy (MRFM) may one day allow for the simultaneous imaging and chemical characterization of a wide range of samples. However, improvements in the mechanical sensitivity of the micromachined cantilevers are needed to realize this possibility. Nestle et al. (83)

comprehensively reviewed the applicability of a mechanical scheme for nuclear magnetic resonance (NMR) detection. They discuss work done on mechanically detected electron spin resonance (ESR), ferromagnetic spin resonance (FMR), and NMR. Even if single-spin resolution is not reached, the MRFM should still be capable of high-resolution magnetic resonance mapping and analysis on very small sample volumes. Notable reports in this area include ESR experiments on a dilute solid solution of diphenylpicrylhydrazyl in polystyrene (84) and FMR experiments on a NiFe film using a torsion mode setup to increase the sensitivity to the weak magnetic forces (85). Nonmechanical- or nonforce-based measurements for detecting magnetic properties include spin-polarized STM. The technique, developed over 10 years ago, uses a magnetic probe tip or a tip with a ferromagnetic thin-film coating as a source for spin-polarized electrons. Heinze and co-workers (86) achieved atomic resolution images of antiferromagnetic domains from manganese atoms on a tungsten (110) surface. Their results show that the spin-polarized electrons map the magnetic superstructure and not the chemical unit cell. Additionally, Pietzsch et al. (87) used a similar technique to determine the magnetic hysteresis in a ferromagnetic thin film. The film consisted of iron nanowires, two atomic layers thick, on a tungsten (110) surface. The researchers were able to observe domain creation and annihilation in this system with nanometer resolution. Magnetic force microscopy (MFM) has constituted the bulk of the research in SPM magnetic imaging. Most of the work has involved increasing the resolution of the technique to allow for viewing of smaller and smaller features. Some of this work has involved the perforation of the magnetically coated tip to form a small pole gap at the end of the tip (88). The MFM signal then arises from the interaction of the field in the gap with the magnetic field gradient of the sample. The perforated tips outperformed conventional MFM probes in their ability to resolve data tracks in recording media. Another approach to improving resolution was to use carbon nanotubes as a MFM probe. The probe consisted of a metal-capped carbon nanotube attached to the tip of a standard Si probe (89, 90). The authors speculated that carbon nanotube probes could achieve spatial resolution of ∼10 nm. The magnitude of magnetic forces have been estimated by a finite element model and numerical simulations (91). Magnetic force magnitudes have been quantified by imaging a calibration sample (92) and using a current ring located in the proximity of the tip (90). Other advances in MFM include inducing a magnetic field at the MFM tip by a microfabricated single turn conductive coil (93) and using the higher flexural modes of the oscillating cantilever for increased sensitivity (94). Berman and co-workers (95) are currently investigating the possibility of a solid-state quantum computer that utilizes inherent properties in STM experiments. Their technique exploits the STM’s ability to detect unpaired electron spins from a single atom and improves upon a previous proposal to create a MRFM-based quantum computer (96). Nanofabrication. The positioning of atoms and molecules on surfaces continues to be actively pursued. Blackledge and coworkers (97) used a palladium-coated SFM tip to chemically modify terminal functional groups on an organosiloxane-coated surface to create biotin-streptavidin assemblies. This technique

resulted in patterns with minimum measured line widths of 33 nm. Diaz and co-workers (98) have devised a new lithographic technique termed redox probe microscopy (RPM) in which a SFM tip is modified with redox-active materials. In this technique, the interactions between the tip and an adsorbate or between the tip and a surface are modulated by means of the electrode potential, allowing for the generation of desired surface structures and patterns. This approach was carried out on a pH-sensitive block copolymer. This technique has been used not only as a stylus but also as a microtweezer to manipulate and position objects. Li and co-workers (99) developed a new electrochemical “dippen” lithography technique that can be used to directly fabricate metal and semiconductor nanostructures on surfaces. This technique has all the advantages of previous “dip-pen” techniques with improved thermal stability. Chemically diverse structures can be made from both organic and inorganic materials. Rangelow and co-workers (100) have designed a new tool for pattern generation and microfabrication based on a scanning micro/nanonozzle. Electrically neutral radicals created in a plasma discharge are pumped through a small tube tapered to a nozzle. A small distance between the nozzle and the surface of the substrate allows a localized interaction. This method of nanolithography/pattern generation leads to less crystal structure damage to the underlying substrate. In another study, Voigt et al. (101) presented the fundamentals for the development of the nanonozzle for direct structuring in the sub-100-nm range. Biology. SPM imaging is finding new and interesting applications in biology. Several excellent reviews of the field have been published during the last two years. Especially noteworthy are reviews on the surface biology of DNA (102), DNA complexation (103), lipid films (104), and protein structure (105). Stolz et al. (106) reviewed the use of time-lapse SFM to examine and manipulate biomolecular assembly events in vitro, providing insight into the mechanisms of fundamental biological processes under both normal and pathological conditions in vivo. Several reports have appeared during the past two years describing sample preparation methods and techniques that enable practitioners of biological SFM to avoid image artifacts. Cherny and Jovin examined the changes in supercoiled DNA configuration induced by varying monovalent/divalent salt concentration (107). SFM imaging of supercoiled DNA molecules deposited onto a mica surface under various salt conditions revealed an apparent relaxation of supercoiling. Changes in the extent of DNA supercoiling were manifested by variation in the number of crossings of double-helical segments. Comparison of SFM images with those obtained with electron microscopy enabled the authors to conclude that the observed changes in DNA configuration are inherent to the DNA structure and are not artifacts arising from the method(s) of sample preparation. Similarly, Camesano and colleagues (108) studied the morphological changes in surface-confined bacterial cells resulting from adhesion-modifying chemistries. Cells were attached to glass slides for tapping mode SFM imaging by cross-linking carboxyl groups on the bacterial surfaces with amine groups that had been covalently attached to glass slides. Comparison of topographic and phase images enabled quantification of the impact of various chemical treatments on cell topography. Analytical Chemistry, Vol. 74, No. 12, June 15, 2002

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Nucleic acid structure continues to be the focus of many SFM imaging studies. Shlyakhtenko and her colleagues (109) gained new insight into the conformation of three-way DNA junctions, intermediates of DNA replication and recombination, from SFM images acquired in vitro. They also observed that the structural transition between cruciform conformations can act as a molecular switch to facilitate or prevent communication between distant regions in DNA (110). Tiner et al. (111) imaged intramolecular DNA triplexes (H-DNA) formed by mirror-repeated purinepyrimidine repeats and stabilized by negative DNA supercoiling. H-DNA appears in images as a clear protrusion with a different thickness compared to a DNA duplex. Consistent with the existing models, H-DNA formation resulted in a kink in the double-helix path with the kink in an acute angle so that the flanking DNA regions are brought in close proximity. SFM is a widely used imaging technique to gain qualitative information on protein binding. In our view, one of the most significant advances in protein imaging was published by Ratcliff and Erie (112). They developed a method for measuring the molecular weight of a protein based on its volume as determined from SFM images. This method enables rapid and accurate analysis of large protein populations and the determination of protein-protein association constants. It is now possible to detect and map the sites of base substitutions in DNA molecules by SFM imaging. The method developed by Tanigawa and co-workers (113) involves incubation of DNA fragment with MutS protein, a protein that recognizes and binds to mismatched base pairs in duplex DNA. Bound MutS protein molecules were readily detected in the image, and their positions along the DNA molecule were determined by measuring the distance from one of the DNA termini. This straightforward method requires a very modest amount of sample and is applicable to short or long DNA fragments. Yoshimura and co-workers (114) imaged the binding of a replication initiator protein, RepE54 to a negatively supercoiled bacterial mini-F plasmid at specific sequences within the replication region. Upon binding, plasmid supercoiling is relaxed without introduction of a DNA strand break or local melting of the DNA double strand. Advances in combinatorial methods and the demand for inparallel analyses have made possible commercial development of DNA and protein microarrays. Currently, verification of a nucleic acid or protein binding event requires detection of a fluorescent or electrochemical taggant at a specific location on the array. O’Brien and co-workers (115) demonstrated the utility of SPM as a tool for rapid and facile screening of multiple protein interactions using massively parallel double-stranded DNA (dsDNA) microarrays. We can only speculate on the rate of sample throughput and commercial feasibility of this approach when coupled to an array of cantilevers capable of in-parallel imaging of portions of the microarray. SENSORS Microcantilevers comprise an emerging sensor platform. The sensing mechanism is straightforward. Molecular adsorption on a resonating cantilever shifts its resonance frequency and changes its surface forces (surface stress). Adsorption onto microcantilevers composed of two chemically different surfaces results in a differential stress between the top and bottom surfaces of the 2856

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cantilever and induces microcantilever bending. Raiteri et al. (116) summarized how cantilever-based sensors can be operated, described their operating principle, and discussed the merits and potential of this emerging sensor platform. Given the current imperatives to develop more sensitive and selective sensors for air-borne and water-borne toxic and pathogenic substances, we anticipate rapid growth in microcantilever-based sensor technology. Microcantilever-based detection of airborne components is the most common application of this sensor platform. Mass sensitivities in the picogram to femtogram range are commonplace with optical reflection as the measurement mode. Several groups have analyzed gas mixtures using differential chemisorption of components onto polymer-coated cantilevers in an array format (117119). Chemisorption of an analyte into the coating produces a mass increase in the layer as well as a change in its interfacial stress. Thus, high-sensitivity detection of individual components can be achieved by monitoring either cantilever deflection or shift in its resonance frequency. Mixture components can be qualitatively and quantitatively identified using principal component regression analysis (120). Thundat and colleagues (121) have investigated an alternative method for determining cantilever deflection. They fashioned deformable diffraction gratings composed of cantilever arrays. Adsorption-induced bending of the cantilever changes the diffraction pattern of a laser beam reflecting off of the array. Quantitative chemical information can be obtained by monitoring the displacement of diffraction peaks as a function of analyte exposure. A compelling feature of microcantilever sensors is that they can be operated in air, vacuum, or liquid. Although the damping effects of liquid medium reduces the resonance response of a microcantilever to a value approximately an order of magnitude smaller than that in air, subnanometer bending of the microcantilever can be readily measured. Fritz and co-workers (122) quantified the interfacial stress of self-assembled monolayers on Au exposed to buffers of various pH values and ionic strengths measured as a function of the liquid environment. The method uses two thiol-modified Au-covered Si cantilevers and a differential method to compensate for thermal and refractive index changes of the liquid environment. Increasing pH and ionic strength leads to bending of a mercaptohexadecanoic acid-covered cantilever compared to a hexadecanethiol-covered reference cantilever. Interfacial stress is highly dependent on the surface density of the ionized moieties in the monolayer. Microcantilevers modified with a cationic self-assembled monolayer respond sensitively to specific anion concentrations (123). High selectivity in cantilever response is achievable through incorporation of biomolecular recognition elements into thin-film coatings on the cantilever. Notable achievements during the past two years include detection of hybridization of complementary oligonucleotides (124), the sensitivity in cantilever response to single-base mismatches (125, 126), and the detection of prostatespecific antigen over a wide range of concentrations in human serum albumin and human plasminogen (127). Ilic and co-workers demonstrated the detection of Escherichia coli cell-antibody binding events with detection sensitivity down to a single cell (128). Their findings portend the use of microcantilever-based sensors for detection of pathogenic bacteria for

medical diagnostics and monitoring the food supply. Tamayo (129) presented a technique for increasing the quality factor of a cantilever immersed in liquid that utilized positive feedback and ac detection of the cantilever response. Q Control enhances the sensitivity of the cantilever response by up to 3 orders of magnitude, and ac detection makes the response signal immune to the long-term drift and temperature variations. Finot and co-workers (130) determined the magnetic susceptibilities of nanogram quantities of paramagnetic materials with a microcantilever sensor. Magnetic force acting on paramagnetic samples attached to the free end of a cantilever produced changes in its deflection and resonance. The magnetic susceptibility measurement is based on comparison of the forces acting on the sample and a reference material in the same magnetic field and field gradient. Measured magnetic susceptibilities showed excellent agreement with literature values. Godin and co-workers (131) presented a method for calculating the surface stress associated with the deflection of a microcantilevers. The method is applicable to both rectangular and triangular cantilevers. Sader investigated the effects of surface stress on the deflections of rectangular cantilever plates (132). This report provided a rigorous finite element analysis of the governing plate equation and the derivation of approximate analytical formulas based on energy minimization techniques. He showed that the clamp can significantly affect the surface stress-induced deflection of the cantilever plate and presented analytical formulas that improve on Stoney’s equation for stress-induced deflection. This work will be especially valuable to researchers involved in optimizing microcantilever-based sensor performance. FORCE SPECTROSCOPY Force spectroscopy has matured in the past few years from an experimental technique practiced by a select few to one widely used by the SPM community. The specialized equipment for force spectroscopy is now commercially available from multiple vendors. The issues of force calibration and force sensitivity have been addressed by manufacturers, allowing for greater confidence in the analyses. Reduction in cantilever dimensions has allowed for the measurement of smaller and smaller forces. This, coupled with a redesign of the optics, has facilitated force measurements in the sub-attonewton range at millikelvin temperatures (133). For researchers working under more temperate conditions, lowpiconewton forces are now routinely measured. Advances in cantilever design continue to push the limits of force detection. Numerous reviews pertaining to all aspects of force spectroscopy have been published during the past two years. Hugel and Seitz (134) have thoroughly reviewed the recent progress of SFMbased single-molecule mechanical testing, emphasizing recent refinements of existing polymer theories and their applicability to interpretation of SFM-based single-molecule mechanical measurements. Zlatanova et al. (135) reviewed instrumental aspects of SFM force measurements. Bustamante and co-workers have reviewed the methods currently used in single-molecule mechanical testing of proteins, nucleic acids, protein-DNA complexes, and chromatin (136). The review by Carrion-Vazquez and coworkers (137) focused on protein folding/unfolding. ClausenSchaumann et al. have highlighted recent progress in singlemolecule force spectroscopy and commented on the prospects of

force spectroscopy in characterizing molecular motors (138). Automated or semiautomated methods of force curve analysis are a continuing area of investigation. Baumgartner et al. (139) developed algorithms for the analysis of force distance curves whereas Gergely et al. (140) developed algorithms detecting rupture points along a force-distance curve. Todd and co-workers (141) have generalized the flexural beam theory for SFM cantilevers to include tip interactions that are present in the snapto-contact region. They have extended their theory to the analysis of continuous force-separation curves (142). Vinogradova and co-workers (143) have theoretically evaluated the possibility of carrying out force measurements (mechanical tests) at much higher speeds than are currently practiced. This has led to the development of a number of models that can be used to estimate the deflection caused by viscous drag on a cantilever in various experiments. The predominance of the work published in force spectroscopy is shifting from model proteins (e.g., titin) to more complex biologically relevant materials. Thompson et al. (144) examined the self-healing mechanism of bone. They found that bone contains sacrificial bonds that both protect and dissipate energy. The recovery of toughness in these pulling experiments paralleled that of titin and nacre, which have been shown to unfold or extend in a similar manner. Binding of multivalent Ca2+ and phosphate ions to sites on collagen molecules forming “sacrificial bonds” in bone were postulated to account for the observed recovery. Bone that had been soaked in Na+ did not show recovery in either tension or compression and served as a control in support of this postulate. Individual bacteriorhodopsin molecules were first extracted from a membrane and then pulled to determine the unfolding pathways of the protein. Oesterhelt et al. (145) first imaged a native purple membrane to locate the bacteriorhodopsin molecules and then pushed the tip into the protein with ∼1 nN of force. This was sufficient to extract the protein from the membrane and leave a vacancy where the protein once was. Subsequent force spectroscopy measurements on the protein revealed that the anchoring forces for the individual helices of the bacteriorhodopsin molecule ranged between 100 and 200 pN. Specific attachment of terminal ends allowed for the resolution of unfolding pathways for individual helices. Oberhauser et al. (146) designed a controlled load apparatus for single-molecule mechanical testing that mimics mechanical testing on bulk samples. Their apparatus operates in a manner that directly probes the mechanical stability of elastic proteins. Mitsui et al. (147) designed a method for performing dynamic measurements as well as quasi-static measurements. During the force extension experiment, a sinusoidal excitation is applied to the molecule in the same manner as with macroscopic viscoelastic measurements for bulk polymers. This is important for mechanical studies on polymers and proteins that have a viscoelastic response since these properties can only be measured dynamically. With their approach, differences between random-coil polymers and proteins with high-order structures can be deduced. Li et al. (148-150) investigated “mechanical phenotypes”, point mutations within the immunoglobulin molecule generated by protein engineering. They demonstrated a previously unrecognized class of phenotypes that may be common in cell adhesion and muscle proteins. Using protein engineering, Li and co-workers Analytical Chemistry, Vol. 74, No. 12, June 15, 2002

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assembled new proteins from three identical repeats of I27-PEVK and showed that the unfolding of tandem modules follows the mechanical stability of the module. This finding enabled the use of the I27 module as a marker for the boundaries of the PEVK segment. With this marker, they were able to determine the persistence and contour lengths of the individual PEVK molecules. Similar protein engineering techniques were used to examine the unfolding of spectrin (151). Clausen-Schaumann et al. examined the kinetics of forceinduced melting and reannealing as well as the influence of ionic strength, temperature, and sequence on the mechanical properties of dsDNA (152). They showed that when dsDNA is overstretched, it begins to melt into single strands that can recombine upon relaxation. Green and Lee (153) have built on their development of tip arrays and tipless cantilevers for force spectroscopy by extending the technique to patterned tip arrays and patterned cantilevers. They use microcontact printing techniques to carefully functionalize a cantilever with both OH and CH3 functionalities. They pattern the tip array in a similar manner and measure the contact forces. Their approach can be extended to probe intermolecular force information on large libraries of molecules. Lo et al. (154) and Yuan et al. (155) have independently analyzed dynamic force spectra of biotin-streptavidin interactions over a range of loading rates. Both observed linear relationships between the unbinding force and the log of the loading rate. Two linear regimes in the dynamic force spectrum were observed, indicating that multiple energy barriers exist in the mechanical detachment of biotin from streptavidin. Hugel et al. (156) investigated the response of single poly(vinylamine) chains of various line charge densities via singlemolecule force spectroscopy. They showed that the electrostatic contribution to polyelectrolyte elasticity diminishes under high mechanical stress. The detachment force of single poly(vinylamine) chains from the silicon oxide surface was a function of the polymer charge density and electrolyte concentration. Krautbauer and co-workers (157) used single-molecule force spectroscopy to characterize DNA-small molecule interactions. Binding of cisplatin and ethidium bromide to duplex DNA produced marked changes in its mechanical properties. Lioubashevski et al. (158) measured hybridization forces between PNA and DNA and detected single-base mismatches. The adhesion force between double-stranded PNA/PNA molecules was 1.8 times larger than double-stranded DNA/PNA. Cocco et al. (159) developed models for the mechanical unzipping of DNA under the conditions used in typical force spectroscopy experiments. Schmitt and colleagues (160) presented a universal anchor system for high-affinity ligand-receptor systems based on Nnitrilotriacetic acid (NTA) binding to His tags. This binding pair requires the presence of a divalent cation. Thus, the molecular interaction can be blocked by addition of EDTA. Mechanical separation of this binding pair in the presence of various cations requires between 22 and 58 pN of force. Marszalek et al. (161) used single-molecule force spectroscopy to identify the components in mixtures of polysaccharides. Using the elasticity of the various polysaccharides as a fingerprint, the force spectra obtained were related to the conformation of the pyranose ring and the type of glycosidic linkages. Their approach 2858

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allows for the identification of individual polysaccharide molecules. To measure the driving forces present during cell division, Matzke et al. (162) probed the stiffening of the cortex of adherent cultured cells along a single scan line during their division. It was discovered via force mapping that cortical stiffening occurs over the equatorial region of the cell ∼160 s before any furrow appears and that stiffening markedly increases as the furrow starts. Oyama and co-workers (163) have analyzed the adhesion properties of cyclodextrins (CyDs) with various guest materials immobilized on a substrate. There was an observed change in the intermolecular interaction between cyclodextrins (CyDs) with guest materials as was detected via changes in the adhesive force. The adhesive force varied with each separate guest material. Bowen and co-workers (164) measured the adhesion properties of single Aspergillus niger spores on mica substrates with SFM. A single spore was immobilized on the apex of the tip. The spore’s adhesive characteristics depended upon environmental factors such as ionic strength and pH. Specific interactions between appendages and protrusions on the spore surface were postulated to play an important role in adhesion. Bowen et al. (165) used a similar technique to characterize the adhesive properties of metabolically active Saccharomyces cerevisiae cells at a hydrophilic mica surface. Dufrene (166) have used chemically modified probe tips (hydrophilic/hydrophobic) to characterize the adhesive properties of Phanerochaete chrysosporium spores. van der Aa and co-workers (167) used force spectroscopy and microscopy to distinguish between dormant and germinating spores. Dormant spores exhibited no surface adhesion while the germinating spores exhibited adhesion forces up to 5.4 N/m. Adhesive interactions were attributed to the stretching of polysaccharides on the cell surface. Dufrene et al. (168) correlated the adhesion of microbial cells with type of organism, physiological state, and environmental conditions. Chen and Moy (169) investigated ligand-receptor binding forces for receptors on the surface of fibroblast cells. Lee and Marchant (170) reported two-dimensional force mapping of human platelets adsorbed on a glass substrate under physiological buffer. Their results provide insight into the mechanism of platelet adhesion and aggregation, which play an integral part in hemostasis and thrombosis. Grandbois and co-workers (171) characterized a mixed layer of type A and O red blood cells based on the adhesive strength of a specific receptor-ligand pair. Adhesion maps afforded discrimination of these blood cell types. Fiorini et al. (172) reported the first direct measurements of competitive binding interactions between an active enzyme (shikimate kinase) immobilized upon the tip and two ligands, one immobilized on the substrate (ATP mimic) and the second in free solution (shikimic acid). Adhesion experiments were carried out in a competitive scheme with a blunt tip to maximize the number of interactions per rupture event. This technique shows great promise for creating a force spectroscopy-based screening method for enzyme inhibition. The potential role of SPM in high-resolution epitope mapping of ligand-receptor binding was also evaluated. Kada and coworkers (173) probed the antigenic binding site of a ryanodine receptor in its physiological environment via force spectroscopic measurements and lateral force mapping. LFM images afforded localization of binding sites with nanometer resolution. Varying

the loading rate in force spectroscopy experiments revealed a logarithmic dependence of the unbinding forces between the antibody-functionalized probe and the ryanodine receptor that ranged from 42 to 73 pN. The authors noted that highly oriented immobilized proteins are required for epitope mapping. Harada and co-workers (174) have investigated control of molecular orientation for mechanical testing of antibody-antigen binding using orientationally specific and random antibody immobilization schemes. Adhesion forces between horse spleen ferritin and the antiferritin Fab fragment of IgG for molecularly oriented molecules greatly exceeded those for randomly oriented molecules. CHARACTERIZATION OF CARBON NANOTUBES Carbon nanotubes are either multiwalled or single-walled and can be either metallic or semiconducting depending on their chirality. SFM has been primarily used for direct imaging, and STM has been used for imaging and characterization of the electronic properties. During the period for which this review encompasses, there have been several outstanding papers on SPM characterizations of nanotubes. Odom et al. (175) performed a thorough investigation of their structural and electronic properties. This work is the basis for the advanced studies presented in the following paragraphs. Ouyang et al. (176, 177) significantly advanced the characterization of SWNT via STM and scanning tunneling spectroscopy (STS). First STM and STS were used to image and characterize junctions on individual SWNT. The atomic structures and electronic properties of metal-semiconductor and semiconductorsemiconductor junctions on individual SWNT were resolved. Spatially resolved STS spectra were obtained across a metalsemiconductor junction. Second, they were able to detect energy gaps in SWNT due to the curvature of the graphene sheet and observed a pseudogap on a (8,8) SWNT bundle. This work has led to the advancement of STM and STS techniques by other researchers in the field. Their technique enables prediction of individual nanotube behavior prior to their assembly in nanoscale devices. Lemay et al. (178) used STM and STS to map the twodimensional structure of individual wave functions in a metallic SWNT. Their results verified that the dispersion relation near the Fermi level is linear. Based on the data obtained, the Fermi velocity and the π-π overlap energy was calculated to be 8.2 ( 0.7 × 105 m s-1 and 2.6 ( 0.2 eV, respectively for the individual SWNT studied. Their results are comparable to those obtained with other techniques that measure bulk properties of nanotube ensembles. The local potential barrier above a carbon nanotube connected to two metal electrodes and switched on by a backside gate was examined using a conductive tip. This tip is able to map a potential variation above the tube with a period of ∼40 nm (179). Transport current was spatially imaged for nanotubes wired between electrodes. It was found that tubes within bundles have weak electronic coupling (180). Characterization and fabrication of a carbon nanotube singleelectron transistor was performed via buckling the nanotube with the SFM tip (181). Local gating of individual nanotubes was also

performed with a conductive SFM tip to manipulate the electrical properties of SWNT circuits (182). The mechanical properties of carbon nanotubes have also been investigated. While most tensile measurement studies on carbon nanotubes have been outside the period covered by this review, work done during this period has focused on the nontensile mechanical measurements. Radial compression of MWNTs showed that they can be reversibly deformed up to ∼40% and that compression increases nonlinearly with applied stress (183). The elastic modulus increases with compression ranging from 9.7 to 80 GPa. The compression strength was greater than 5.3 GPa for a 10-nm-diameter MWNT (184). Collapsed MWNTs or nanotube ribbons are extremely flexible and readily conform to an underlying substrate (185). Coiling of MWNTs was observed; the helical shape has little effect on the measured Young’s modulus. Typical values for Young’s modulus were 0.4-0.9 TPa (186). Rolling of carbon nanotubes while on highly ordered pyrolytic graphite (HOPG) follows a gearlike motion. This motion is governed by an overlap of the hexagonal graphite surfaces of the carbon nanotube and the HOPG. Interlocking of the atomic lattices increases the force required to move the carbon nanotube, and the result is the nanotube “locks” into a gearlike motion. As a nanotube is rotated in plane, the resulting “lock” into gearlike motion occurs every 60°, consistent with theoretical predictions (187). The electronic properties of nanotubes, either under or after applied strain, have also been a research focus. In situ measurements of the electronic properties of carbon nanotubes under stress have shown that the conductance in a SWNT drops by 2 orders of magnitude when deformed by an SFM tip. This is consistent with the reversible formation of sp3 bonds during the mechanical deformation (188). Other studies measured the resistance of induced defects such as closely separated kinks in a SWNT (189). These defects were found to have a resistance from 10 to 100 kΩ and even showed single-electron charging behavior. The electronic behavior of carbon nanotubes has led to their use in single-electron transistors (181). At the conclusion of our previous review, we predicted that carbon nanotube tips would revolutionize scanning probe microscopy. This prediction was based on the size, shape, mechanical properties, robustness, and ease with which they can be chemically modified. Although the availability of nanotube tips is still somewhat limited, recent applications support our prediction. For example, Watanabe et al. (190) reported the ingenious use of SWNTs to probe the electrical conductivity of a single DNA molecule. A pair of SWNTs function as a “nanotweezer” and a third nanotube is attached to a conducting SFM tip. The nanotubes afford electrical contact to the molecule and serve as the source, gate, and drain terminals. As the gate bias voltage was increased, the voltage gap region in the current-voltage curves decreased, demonstrating that the DNA molecule is serving as a switching device when the gate is biased. This work clearly exemplifies the unique role carbon nanotubes and SPM can and will play in molecular architecture and the design of nanoscale electronic devices. Analytical Chemistry, Vol. 74, No. 12, June 15, 2002

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Mark A. Poggi is a graduate student completing his doctoral degree in analytical chemistry at the Georgia Institute of Technology. He obtained his baccalaureate degree in chemistry at Michigan State University. His current research interests include single-molecule mechanical testing and SFM imaging of drug-DNA interactions. Lawrence A. Bottomley is Professor of Chemistry at the Georgia Institute of Technology. He obtained his baccalaureate degree in chemistry at California State University, Fullerton, and his doctoral degree in analytical chemistry at the University of Houston. His current research interests include the biological and nanotechnological applications of scanning probe microscopy and electrochemistry. Peter T. Lillehei is materials research engineer with the Advanced Materials and Processing Branch at the NASA Langley Research Center. He holds a bachelors degree in chemistry and chemical engineering from the University of Minnesota and a doctoral degree in analytical chemistry from Georgia Tech. His current research interests include single-molecule mechanical testing of biopolymers and applications of carbon nanotubes.

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