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Potential of gold-bound microtubules as a new ultrasound contrast agent.

Contrast agents based on gas-filled microspheres share the problem of time limited opacification due to low stability of microbubbles. The aim of this study was to test if gold-bound microtubules provide backscattering that allows microtubules to be potentially useful as an ultrasound (US) contrast agent. Gold colloids were immobilized on protein microtubule walls. Latex balloons were filled with gold-bound microtubules or conventional left heart contrast agent and were ultrasonographically imaged in fundamental and harmonic modes. Feasibility of anti-beta-tubulin antibody conjugation to gold-bound microtubules was confirmed using immune fluorescence analysis. Gold particles were successfully bound to microtubules. Contrast intensities in latex balloons filled with gold-bound microtubules (141 +/- 35) were comparable to those with Levovist (180 +/- 35) and did not decrease significantly during continuous US imaging for 20 min (135 +/- 34 vs. Levovist 5.0 +/- 2.0). Anti-beta-tubulin antibodies were successfully conjugated to gold-bound microtubules. Gold-bound microtubules provide a persistent contrast effect, suggesting their use as an ultrasonic contrast agent with the feasibility of antibody conjugation.

Animals↗

AFM imaging in solution of protein-DNA complexes formed on DNA anchored to a gold surface.

A chemical procedure for anchoring DNA molecules to gold surfaces was used to facilitate the imaging of DNA and DNA-protein complexes in buffer solution by tapping mode atomic force microscopy (TMAFM). For preparing flat gold surfaces, a novel approach was employed by evaporating small amounts of gold onto freshly cleaved mica to give flat films that were stable under aqueous buffer conditions. The thickness of the investigated films ranged from 1 to 10 nm. For typical films of 4-6 nm, which were stable under aqueous buffer conditions, the root mean square (RMS) roughness ranged between 0.25 and 0.5 nm, as measured by atomic force microscopy (AFM). This roughness is comparable to that of obtained by the template stripped gold (TSG) technique, which is widely used in scanning probe microscopy but involves more preparation steps. In order to visualize DNA and DNA-protein complexes by TMAFM, the DNA was chemisorbed to the gold surface through a linker carrying a terminal thiol group at the 5'-end of each of the DNA strands. The modified DNA fragments were bound to the gold films and imaged in buffer solution, while unmodified DNA could not be visualized. Since the DNA was not dried during the process, it can be assumed that its native conformation was retained. This mode of anchoring did not prevent interaction with proteins, as confirmed by the observation that the topology of a complex formed by adding the protein to a surface-anchored DNA was the same as that obtained by anchoring a pre-formed complex to the gold surface. We attribute this observation to the fact that the DNA is anchored to the gold surfaces only through its ends, therefore the DNA-support interaction is minimized but imaging is still possible.

Bacterial Proteins↗

Protein nanopatterns and biosensors using gold binding polypeptide as a fusion partner.

An efficient strategy for immobilizing proteins on a gold surface was developed by employing the gold binding polypeptide (GBP) as a fusion partner. Using the enhanced green fluorescent protein (EGFP), severe acute respiratory syndrome coronavirus (SARS-CoV) envelope protein (SCVme), and core streptavidin (cSA) of Streptomyces avidinii as model proteins, specific immobilization of the GBP-fusion proteins onto the gold nanoparticles and generation of protein nanopatterns on the bare gold surface were demonstrated. The GBP-fused SCVme bound to gold nanoparticles successfully interacted with its antibody and showed changes in absorbance and color, allowing efficient diagnosis of SARS-CoV. The fusion proteins could be successfully immobilized on the gold surface by nanopatterning and microcontact printing as examined by atomic force microscopy and surface plasmon resonance analysis. The poly(dimethylsiloxane) microfluidic channels were created on the gold surface and were used for antigen-antibody and DNA-DNA interaction studies. Specific immobilization of GBP-EGFP fusion protein and its interaction with the antibody in the microchannels could be demonstrated. By immobilizing the DNA probe through the use of GBP-fused cSA, specific hybridization of the target DNA prepared from Salmonella could also be achieved. The GBP-fusion method allows immobilization of proteins onto the gold surface without surface modification and in bioactive forms suitable for studying protein-protein, DNA-DNA, and other biomolecular interaction studies. Furthermore, these studies can be carried out in a microfluidic system, which allows high-throughput analysis of biomolecular interactions.

Biological Assay↗

Identification of active sites in gold-catalyzed hydrogenation of acrolein.

The active sites of supported gold catalysts, favoring the adsorption of C=O groups of acrolein and subsequent reaction to allyl alcohol, have been identified as edges of gold nanoparticles. After our recent finding that this reaction preferentially occurs on single crystalline particles rather than multiply twinned ones, this paper reports on a new approach to distinguish different features of the gold particle morphology. Elucidation of the active site issue cannot be simply done by varying the size of gold particles, since the effects of faceting and multiply twinned particles may interfere. Therefore, modification of the gold particle surface by indium has been used to vary the active site characteristics of a suitable catalyst, and a selective decoration of gold particle faces has been observed, leaving edges free. This is in contradiction to theoretical predictions, suggesting a preferred occupation of the low-coordinated edges of the gold particles. On the bimetallic catalyst, the desired allyl alcohol is the main product (selectivity 63%; temperature 593 K, total pressure p(total) = 2 MPa). From the experimentally proven correlation between surface structure and catalytic behavior, the edges of single crystalline gold particles have been identified as active sites for the preferred C=O hydrogenation.

Acrolein↗

Antitumor activity of the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I).

The title compound has been designed for antitumor activity based on structural features of related known antitumor gold agents, that is, gold-monophosphine and gold-diphosphine derivatives. It is a gold complex that contains both types of phosphine ligands, thus suggesting a possible synergistic action. The results of a single crystal X-ray structure determination of this molecule show the metal surrounded by 3 P atoms and one Cl anion in a distorted tetrahedral arrangement. The chloro anion, however, is weakly bound to the metal and so the species shows ionic character. The P NMR study, performed in solution, confirms the structural features observed in the solid and, in addition, indicates partial formation of other known gold(I)-diphosphine antitumor agents. The ionic character and strong Au-P bonds of this novel gold(I) species are similar to those of the most active antitumor gold compounds so far studied. The former feature contributes to solubility in biological fluids, and the latter prevents fast biomolecular attack. In addition, the title compound is less lipophilic, a feature recently correlated to lower liver toxicity. The title compound shows in vitro antitumor activity in the two initial National Cancer Institute protocols against human tumors. In the first screening, a unique dose (0.10 mM) of the title compound reduced cell growth of MCF7 (breast cancer), NCI-H460 (lung cancer), and SF-268 (Central Nervous System cancer-CNS) to 5, 8, and 11%, respectively. In the second protocol a 60-cell line panel was analyzed with the title compound concentration in the 0.1 mM-0.01 microM range. The highest activity was for the breast tumor cell line MCF7 with a LC(50) less than 0.01 microM. LC(50) values in the micromolar range were obtained for 29 cell lines. With the exception of leukemia, these micromolar activities were observed in at least one cell line for each subgroup tumor (non small lung, colon, CNS, melanoma, renal, prostate, breast, and ovarian). The leukemia inactivity was unexpected, as all antitumor gold(I) phosphine compounds in the literature described thus far are active. Melanoma was the most sensitive subgroup screened (five out of seven cell lines).

Antineoplastic Agents↗

Characterization of single- and double-stranded DNA on gold surfaces.

Single- and double-stranded deoxy ribonucleic acid (DNA) molecules attached to self-assembled monolayers (SAMs) on gold surfaces were characterized by a number of optical and electronic spectroscopic techniques. The DNA-modified gold surfaces were prepared through the self-assembly of 6-mercapto-1-hexanol and 5'-C(6)H(12)SH -modified single-stranded DNA (ssDNA). Upon hybridization of the surface-bound probe ssDNA with its complimentary target, formation of double-stranded DNA (dsDNA) on the gold surface is observed and in a competing process, probe ssDNA is desorbed from the gold surface. The competition between hybridization of ssDNA with its complimentary target and ssDNA probe desorption from the gold surface has been investigated in this paper using X-ray photoelectron spectroscopy, chronocoulometry, fluorescence, and polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS). The formation of dsDNA on the surface was identified by PM-IRRAS by a dsDNA IR signature at approximately 1678 cm(-)(1) that was confirmed by density functional theory calculations of the nucleotides and the nucleotides' base pairs. The presence of dsDNA through the specific DNA hybridization was additionally confirmed by atomic force microscopy through colloidal gold nanoparticle labeling of the target ssDNA. Using these methods, strand loss was observed even for DNA hybridization performed at 25 degrees C for the DNA monolayers studied here consisting of attachment to the gold surfaces by single Au-S bonds. This finding has significant consequence for the application of SAM technology in the detection of oligonucleotide hybridization on gold surfaces.

DNA↗

Effect of hydrophobicity inside PEO-PPO-PEO block copolymer micelles on the stabilization of gold nanoparticles: experiments.

In this paper we present the effect of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer micelles and their hydrophobicity on the stabilization of gold nanoparticles. Gold nanoparticles were prepared by a method developed by Sakai et al. (Sakai, T.; Alexandridis, P. Langmuir 2004, 20, 8426). An absorption centered at 300-400 nm in time-dependent UV spectra provided evidence that the very first step of the synthesis was to form primary gold clusters. Then the gold clusters grew in size and were stabilized by block copolymer micelles. The stabilization capacities of the micelles were modulated by tuning the block copolymer concentration and composition and by adding salts. With good stabilization, gold particles were spherical and uniform in size with a diameter of 5-10 nm. Otherwise they were aggregates with irregular shapes such as triangular, hexagonal, and rodlike. The presence of a small amount of NaF significantly increased the stabilization capacity of the micelles and consequently modified the quality of the gold particles. Using FTIR and 1H NMR spectroscopy, micellization of the block copolymers and hydrophobicity of the micelles were proven very important for the stabilization. A higher hydrophobicity of the micelle cores was expected to favor the entrapment of primary gold clusters and the stabilization of gold nanoparticles.

Colloids↗

The SERS and TERS effects obtained by gold droplets on top of Si nanowires.

We show that hemispherical gold droplets on top of silicon nanowires when grown by the vapor-liquid-solid (VLS) mechanism, can produce a significant enhancement of Raman scattered signals. Signal enhancement for a few or even just single gold droplets is demonstrated by analyzing the enhanced Raman signature of malachite green molecules. For this experiment, trenches (approximately 800 nm wide) were etched in a silicon-on-insulator (SOI) wafer along <110> crystallographic directions that constitute sidewalls ({110} surfaces) suitable for the growth of silicon nanowires in <111> directions with the intention that the gold droplets on the silicon nanowires can meet somewhere in the trench when growth time is carefully selected. Another way to realize gold nanostructures in close vicinity is to attach a silicon nanowire with a gold droplet onto an atomic force microscopy (AFM) tip and to bring this tip toward another gold-coated AFM tip where malachite green molecules were deposited prior to the measurements. In both experiments, signal enhancement of characteristic Raman bands of malachite green molecules was observed. This indicates that silicon nanowires with gold droplets atop can act as efficient probes for tip-enhanced Raman spectroscopy (TERS). In our article, we show that a nanowire TERS probe can be fabricated by welding nanowires with gold droplets to AFM tips in a scanning electron microscope (SEM). TERS tips made from nanowires could improve the spatial resolution of Raman spectroscopy so that measurements on the nanometer scale are possible.

Gold↗

Dental gold alloys and contact hypersensitivity.

A total of 172 patients referred to the Norwegian National Adverse Reaction Group were patch-tested with a dental series. Of these, 25% showed a positive reaction to gold sodium thiosulfate or potassium dicyanoaurate. There was a statistically significant correlation (p=0.0019) between the presence of dental gold and a positive patch test to gold. There was a statistically significant correlation between ear piercing and a positive patch test to gold (p=0.04). In most cases, we did not find clinical correlates to positive patch tests to gold. 2 patients with objective and subjective oral/perioral and general symptoms are described as case reports. Their symptoms disappeared when gold restorations were removed. We conclude that there is an overrepresentation of gold allergies among those with dental restorations containing gold.

Adult↗

Assessment of silver and gold substrates for the detection of amphetamine sulfate by surface enhanced Raman scattering (SERS).

Methods of detection of amphetamine sulfate using surface enhanced Raman scattering (SERS) from colloidal suspensions and vapour deposited films of both silver and gold are compared. Different aggregating agents are required to produce effective SERS from silver and gold colloidal suspensions. Gold colloid and vapour deposited gold films give weaker scattering than the equivalent silver substrates when high concentrations of drug are analysed but they also give lower detection limits, suggesting a smaller surface enhancement but stronger surface adsorption. A 10(-5) mol dm(-3) solution (the final concentration after addition of colloid was 10(-6) mol dm(-3)) of amphetamine sulfate was detected from gold colloid with an RSD of 5.4%. 25 microl of the same solution could be detected on a roughened gold film. The intensities of the spectra varied across the film surface resulting in relatively high RSDs. The precision was improved by averaging the scattering from several points on the surface. An attempt to improve the detection limit and precision by concentrating a suspension of gold colloid and amphetamine sulfate in aluminium wells did not give effective quantitation. Thus, positive identification and semi-quantitative estimation of amphetamine sulfate can be made quickly and easily using SERS from suspended gold colloid with the appropriate aggregating agents.

Amphetamine↗

Gold and D-penicillamine induce vasculitis and up-regulate mRNA for IL-4 in the Brown Norway rat: support for a role for Th2 cell activity.

D-penicillamine (DP) and gold salts which are used as immune-modulating agents in the treatment of rheumatoid arthritis are known to be capable of causing autoimmune manifestations. Most autoimmune diseases in man are dominated by Th1-type responses, and one might presume that effective immunotherapy counteracts Th activity, perhaps by causing a shift to a Th2 response. The mechanism of action of gold and DP is not clear, but some clues may be obtained from their effects in animal models. DP, gold salts and mercuric chloride (HgCl2) are known to induce Th2-dominated autoimmune syndromes in genetically susceptible rodent strains, and we have demonstrated recently that HgCl2 up-regulates messenger RNA (mRNA) for IL-4 in the Brown Norway (BN) rat. In the BN rat HgCl2 treatment is also associated with the development of vasculitis, and anti-myeloperoxidase (MPO) antibodies are found in the serum. The present study examined and confirmed the hypothesis that, since gold and DP induce an autoimmune syndrome similar to HgCl2 in the BN rat, they may also induce vasculitis and an up-regulation in mRNA for IL-4. Tissue injury was assessed macroscopically and histologically on day 5 and day 15 after the start of injections with gold, DP or HgCl2, serum titres of IgE and presence of anti-MPO antibodies were determined using ELISA, and a semi-quantitative assay using reverse transcription-polymerase chain reaction was used to assay the level of mRNA for IL-4 in spleen and caecum. The relative degree of tissue injury reflected the potency of induction of IgE by the three agents (HgCl2 being most potent and DP least potent). The lesions were identical histologically, supporting the premise that the vasculitis is a manifestation of the autoimmune syndrome rather than non-specific HgCl2 toxicity. Both gold and DP induced less up-regulation of mRNA for IL-4 than HgCl2. HgCl2 (but not gold or DP) induced anti-MPO antibodies. It would be interesting to examine patients treated with gold and DP to see if there is evidence of a Th2-type response in those developing autoimmune complications, and whether or not the bias to a Th2 environment contributes to efficacy of treatment of the underlying disease.

Animals↗

Prospective studies of thyroid function in patients receiving gold therapy.

Gold inhibits the Type I deiodinase that provides the bulk of circulating T3 in humans. We prospectively studied thyroid function in patients receiving increasing parenteral cumulative gold doses. Eight consecutive euthyroid patients with rheumatoid or psoriatic arthritis who were initiating intramuscular gold therapy were enrolled. Serum thyroid hormone levels (total T4, T3, and rT3) and TSH were measured for each subject at various levels during gold therapy. For analysis, the free T4 and free T3 indices, TSH concentrations, and T4/T3 ratios were correlated with cumulative gold dose. Neither individual nor pooled linear regressions showed a significant correlation between cumulative gold dose and any of the thyroid function parameters. Thyroid function is not affected in patients receiving up to 1500 mg of gold compounds. The most likely explanation for this is that gold principally accumulates in the Kupffer cells and renal cortex and these cells do not express Type I deiodinase.

Adult↗

Blood and urine gold levels during chrysotherapy for rheumatoid arthritis.

In this study the value of undertaking routine blood and urine estimations was assessed in relation to achieving maximum efficacy and safety in chrysotherapy. It was found that a favourable response to gold was forthcoming in approximately two-thirds of patients and occurred irrespective of the patients' disease duration or severity, or the mean serum gold level or the mean urinary gold excretion, estimated immediately before the next gold injection was due. The presence of rheumatoid nodules and the patients' advancing age were associated with a less favourable clinical response to gold. Those patients who derived a marked benefit from chrysotherapy did so significantly earlier in their course than those who derived only moderate benefit. A frequent correlation was seen in individual patients between serum gold levels and urinary gold excretion. This was most marked in those patients showing a favourable response to gold.

Adult↗

Long-term comparison of a newly designed gold implant with the conventional implant in facial nerve paralysis.

Patients with complete facial nerve palsy are at risk for eye complications resulting from exposure of the cornea and loss of the blinking reflex. Failure of protection predisposes the patient to exposure keratitis, corneal abrasion and, in rare cases, blindness. The mainstays of non-surgical therapy are cumbersome, obscure vision, and are mostly helpful in patients with acute facial paralysis in whom recovery of orbicularis oculi function is expected. Methods of lid-loading using metal implants and gold eyelid weights have been reported in the literature. Between October of 1988 and March of 1995, 32 patients with lagophthalmos due to facial nerve palsy underwent a total of 34 procedures for the insertion of a gold eyelid weight. Each patient had a gold weight inserted into a small pocket between the orbicularis oculi and the tarsal plate of the upper eyelid. The gold implant is curved to fit the curvature of the eye and contains holes for fixation to the tarsus with sutures. Ingrowth of fibrous tissue through the holes may also help fix the weight in position. Between 1988 and 1991, 10 patients received 10 commercially available rectangular gold implants with 2 holes; these implants resulted in adverse effects, such as infection and exposure in up to 30 percent of the cases. Because of the high complication rate with the rectangular gold implant, the authors began using a new, elliptical gold implant with 3 holes, which is longer, thinner, wider in the center, and narrower in the peripheral portion. This new elliptical implant was used on 22 patients (24 implants) from December of 1991 through March of 1995. The mean follow-up time for the 32 patients in the study was 41.3 months (range, 6 to 63 months), 49.8 months for patients with rectangular implants and 32.8 months for patients with elliptical implants. The elliptical gold implant resulted in dynamic closure of the eyelid and in excellent protection and cosmesis. Lagophthalmos and exposure keratitis resolved, visual acuity significantly improved without complications, and most patients could dispense with eyedrops and salves. A lower eyelid supporting procedure (conchal cartilage graft) should be performed simultaneously in patients with lagophthalmos of a moderate or severe degree to achieve complete closure of the eyelid. Use of a tall pillow decreased the incidence of eyelid opening during sleep. Double eyelid fold operations'were performed on the contralateral eyelid after 6 months, resulting in a symmetrical and beautiful eyelid.

Adolescent↗

Long-term outcome of gold eyelid weights in patients with facial nerve palsy.

OBJECTIVE: To assess the safety and efficacy of upper eyelid gold weight implants in managing paralytic lagophthalmos and to compare two surgical techniques for their insertion. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: One hundred four patients had a gold weight implanted for paralytic lagophthalmos between 1982 and 1996 at the Royal Prince Alfred Hospital in Sydney. Each patient had more than 2 years of follow-up of lid load function. MAIN OUTCOME MEASURES: The effectiveness of gold weights in reanimating eyelid closure, mean duration of gold weight retention, reasons for removal, and complications resulting from a gold weight; these outcomes were also compared using two surgical techniques for gold weight insertion. RESULTS: One hundred three patients maintained corneal integrity. At the time of assessment, 46 patients had had their lid loads removed from their eyelids, and 58 lid loads remained in situ. Of the lid loads that were removed, 78% were because the facial nerve had recovered. The remaining 22% were removed because of cosmetic dissatisfaction (7 patients), the lid load becoming too superficial (6 patients), migration (3 patients), partial extrusion (1 patient), and ptosis resulting from too heavy a weight (1 patient). CONCLUSION: Gold weights are well tolerated and effective in managing paralytic lagophthalmos. An open surgical technique with direct suture fixation of the gold weight to the tarsal plate produced fewer complications than inserting the lid load into a prefashioned tissue pocket in the preseptal space through a small lateral skin incision.

Adult↗

Gold weight implantation: a better way?

PURPOSE: To introduce an alternative surgical technique for gold weight implantation for the treatment of lagophthalmos. We suggest that unwrapped intraorbital gold weight implantation provides adequate function, better cosmetic appearance, and lower morbidity than conventional implantation with wrapped or unwrapped pretarsal gold weights. METHODS: The charts of a single surgeon were reviewed (1994 to 2003). All patients who underwent intraorbital gold weight implantation were included in the study. The technique was noted to be consistent with intraorbital fixation of a custom 2.2-gm gold weight (MedDev Corporation, Sunnyvale, California). Implants were not wrapped. Efficacy was defined as elimination of exposure keratopathy with preservation of the visual axis. Morbidity was defined as extrusion of the weight, shift of positioning requiring intervention, inflammation/infection of the eyelid, or poor cosmetic appearance. RESULTS: Of 59 patient charts reviewed, 2 patients had morbidity as defined by our study: One had shifting of the gold weight, necessitating repositioning of the weight; the other had extrusion of the gold weight, requiring its removal. The remaining patients had no complaints or cosmetic concerns. Follow-up examinations found no incidence of exposure keratopathy. CONCLUSIONS: We found intraorbital gold weight implantation, without the use of a wrap, to be simple and effective, with adequate function, an acceptably low postoperative morbidity rate, and an excellent cosmetic outcome.

Adolescent↗

Selective binding of colloidal gold-protein conjugates to epidermal phosphorus-rich keratohyaline granules and cornified cells.

Colloidal gold solutions conjugated with staphylococcal protein A (SpA) are widely used in high-resolution immunocytochemical studies to visualize antibodies bound at antigenic sites. Here we report that colloidal gold solutions conjugated with SpA, bovine serum albumin (BSA), or gelatin bind selectively to structures in glutaraldehyde-fixed, plastic-embedded epidermis of rabbit, mouse, and human. Two types of keratohyaline granules are present in epidermis, a phosphorus-rich (PR) and a sulphur-rich (SR) type. The PR keratohyaline granules were strongly labeled with gold particles, whereas SR keratohyaline granules or other structures in the living cells of epidermis were unlabeled. The PR keratohyaline granules are assumed to be precursors of the matrix protein of cornified cells, and intense gold labeling occurred over the lower layer of cornified cells (i.e., stratum lucidum). More superficial cornified cells were weakly labeled or unlabeled. The gold labeling pattern was identical whether SpA, BSA, or gelatin was used to stabilize the colloidal gold solution. The mechanism of binding of protein-conjugated gold to PR keratohyaline granules and matrix protein of cornified cells is not clear. It is speculated that the charged gold particles are not completely coated by the stabilizing protein, allowing for an electrostatic interaction with charged proteins in sections of cells.

Animals↗

Calibration of the scanning (atomic) force microscope with gold particles.

Scanning force microscopy (SFM) holds great promise for biological research. Two major problems that have confronted imaging with the scanning force microscope have been the distortion of the image and overestimation in measurements of lateral size due to the varying geometry and characteristics of the scanning tip. In this study, spherical colloidal gold particles (10, 20 and 40 nm in diameter) were used to determine (1) tip parameters (size, shape and semi-vertical angle); (2) the distortion of the image caused by the tip; and (3) the overestimation or broadening of lateral dimensions. These gold particles deviate little in size, are rigid and have a size similar to biological macromolecules. Images of the colloidal gold particles by SFM were compared with those obtained by electron microscopy (EM). The height of the gold particles as measured by SFM and EM was comparable and was little affected by the tip geometry. The measurements of the lateral dimensions of colloidal gold, however, showed substantial differences between SFM and EM in that SFM resulted in an overestimate of the lateral dimensions. Moreover, the distortion of images and broadening of lateral dimensions were specific to the SFM tip used. The calibration of the SFM tip with mica provided little clue as to the type of distortion and the amount of lateral broadening observed when the larger gold particles were scanned. The SFM image also depended on the orientation of the tip with respect to the specimen. Our results suggest that quantitative SFM imaging requires calibration to identify and account for both the distortions and the magnitude of lateral broadening caused by the cantilever tip. Calibration with gold particles is fast and nondestructive to the tip. The raw imaging data of the specimen can be corrected for the tip effect and true structural information can be derived. In summary, we present a simple and practical method for the calibration of the SFM tip using gold particles with a size in the range of biomacromolecules that allows: (1) selection of a cantilever tip that produces an image with minimal distortion; (2) quantitative determination of tip parameters; (3) reconstruction of the shape of the tip at different heights from the tip apex; (4) appreciation of the type of distortion that may be introduced by a specific tip and quantification of the overestimation of the lateral dimensions; and (5) calculation of the true structure of the specimen from the image data. The significance is that such calibration will permit quantitative and accurate imaging with SFM.

Calibration↗