Frank Paul

A quartz crystal resonant sensor (QCRS) study of HSA--drug interactions.

Human serum albumin (HSA) was immobilised on the gold surface of a quartz crystal resonance sensor (QCRS) and exposed to warfarin and diazepam. Distinct decreases in frequency of differing magnitudes were observed upon exposure of the protein to each of the compounds suggesting strongly that a ligand interaction was occurring. Moreover, as sequential exposure in any order was observed to yield distinct repeatable frequency decreases for the ligands indicated, screening for site specific binding may be possible. Identically immobilised bovine serum albumin (BSA) gave no response to either compound.

Real-time monitoring of stain formation and removal on calcium hydroxyapatite surfaces using quartz crystal sensor technology

Stain formation, stain inhibition and stain removal may be monitored in real-time using a novel method employing a quartz crystal resonance sensor (QCR), based upon quartz crystal microbalance (QCM) technologies. Crystalline hydroxyapatite (HA) surfaces were prepared on phosphate-terminated, polymer-modified gold surfaces of quartz crystal transducers. The resulting sensors were placed in a specially constructed flow cell, and the interaction of adsorbates from the tea stain solution monitored as a function of time. The ability of sodium tripolyphosphate (STP) to remove extrinsic stain and also to inhibit its formation was examined. The adsorption of material from the staining solution passed over the sensor was clearly observable, and once bound, the crystal based real-time data suggest that tea adsorbates were not removed in the absence of an active under conditions of continuous flow. STP was shown to rapidly remove existing stain, and exhibited a clear inhibitory action on stain formation irrespective of whether the HA had been previously exposed to tea chromogens. The continuous data generated by the QCR technique were in good agreement with the results obtained using a discontinuous spectrophotometric method. The presently described quartz crystal model for extrinsic dental stain should provide a valuable tool to aid understanding of the interactions of staining agents with a crystalline HA surface as a model tooth surface, and to evaluate the efficacy and mode of action of STP and putative stain removal agents.

Vitamin C induced decomposition of lipid hydroperoxides: direct evidence of genotoxin–DNA binding detected by QCRS

We report direct evidence for human DNA-binding to precursors of mutagenic lesion-inducing compounds, produced form the vitamin C induced decomposition of lipid hydroperoxides, using a quartz crystal resonant sensor assay.

Quartz crystal resonant sensor (QCRS) model for label-free, small molecules—receptor studies

Studying the binding mechanisms of potential drug candidates to receptors of interest is of huge importance to the pharmaceutical industry and laboratory workers worldwide. Reliable arrangements for following interactions between low molecular weight samples and their potential receptors without the requirement for labelling are uncommon. Quartz crystal resonant sensors (QCRS) are becoming established as label-free tools for observing the interactions between species in liquid media. Here we describe a new model based upon QCRS technology and novel thiol surface chemistry, capable of detecting the interactions between low molecular weight sugars and their host receptors in real-time.

Characterisation of small molecule binding to DNA using a quartz crystal resonant sensor

A new development in quartz crystal resonant sensor (QCRS) technology allows real-time analysis of binding by small molecules to DNA and has been tested using superoxide dismutase mimics.

Real-time monitoring of cellular integration within bulk soft tissue scaffold materials

A non-invasive, real-time acoustic method for the monitoring of cellular integration within commercial collagen-based dermal replacement scaffolds is reported for the first time. An unexpectedly high degree of acoustic energy transfer through heavily hydrated thick film (up to 0.5 mm) sections of collagen/glycosaminoglycan scaffold material intimately associated with a quartz crystal sensor allowed quantitative resonant frequency measurements upon application of fibroblast cell suspensions to the material. Changes in resonant frequency and energy dissipation were commensurate with cellular interaction with the gel.

Real-time evaluation of macromolecular surface modified quartz crystal resonant sensors under cryogenic stress for biological applications.

This study presents a novel auto-gain-control based quartz acoustic sensor technology capable of constant quartz crystal operation when cycled between ambient (22 degrees C) and cryogenic temperatures (-196 degrees C), afforded by direct exposure of crystals to bulk liquid nitrogen. The real-time frequency response profiles due to freeze-thaw cycling on crystals of differing surface finish and two model macromolecular surface coatings were studied in order to determine surface events such as water uptake. The quartz crystal surface finishes used were optically polished or lapped to one of two surface finishes. These were used as control native gold electrodes, and these surfaces were further coated with bovine serum albumin or the tri-block copolymer, poloxamer-188 as model macromolecular surface architectures. Crystals were snap frozen in liquid nitrogen and allowed to return to ambient temperature under controlled conditions. The processes of ice formation, thawing and evaporation were followed in real-time and comparisons were made between the test samples in order to assess the capability of this technique for sensing changes in surface characteristics such as the entrapment of water.

Development of novel liquid phase qcrs sensor technology

This paper discusses the development of novel liquid phase quartz crystal resonant sensor technologies for label free, real-time detection of pharmaceutical applications.New crystal oscillator technologies are introduced alongside crystal mounting and flow cell designs circumventing more traditional approaches to yield greater robustness, reliability and sensitivity. Data for standardised long-term experiments is presented and analysed with respect to reproducibility and stability and comparisons made with surface plasmon resonance.

Determination of the surface tension of block copolymer micelles by phagocytosis

AbstractPurpose. This work was carried out to determine the surface tension of block copolymer micelles of 14C labelled ABA poly (oxyethylene-bi-isoprene-b-oxyethylene) which have a long circulating half life in animals. Methods. The method used was that of phagocytosis. The percentage of micelles phagocytosed by human mononuclear cells was determined in solutions of different surface tension. Results. The values obtained were 72 mN/m which may be predicted for a particle with a long circulating half life in animals. The method also gave an estimate of the surface tension for the mononuclear cells. Conclusions. This technique has the advantage of determining the surface tension of highly hydrated small particles including stable micelles in an environment similar to that in which they normally exist.

Synthesis and characterisation of N-(3-dihydroxyborylphenyl)-5-mercaptopentanamide: a novel self-assembling vicinal diol receptor

A novel self-assembling vicinal diol receptor, N-(3-dihydroxyborylphenyl)-5-mercaptopentanamide, has been synthesised via a three step procedure, characterised by NMR, mass spectoscopy and FTIR spectroscopy and shown to be functionally active by contact angle analysis, surface plasmon resonance and QCM.