Mark Platt | Loughborough University (original) (raw)

Papers by Mark Platt

Resistive pulse sensors have been used to characterise everything from whole cells to small molec... more Resistive pulse sensors have been used to characterise everything from whole cells to small molecules. Their integration into microfluidic devices have simplified sample handling whilst increasing throughput. Typically, these devices measure a limited size range or a specific analyte, making them prone to blockages in complex sample matrixes. To prolong their life and facilitate their use, samples are often filtered or prepared to match the sample with the sensor diameter. Here, we advance our tuneable flow resistive pulse sensor which utilises additively manufactured parts. The sensor allows parts to be easily changed, washed and cleaned, its simplicity and versatility allows components from existing nanopore fabrication techniques such as silicon nitride, polyurethane and glass pipettes to be integrated into a single device. This creates a multi-nanopore sensor that can simultaneously measure particles from 0.1 to 30 m in diameter. The orientation and controlled fluid flow in the...

Sensors

DNAzymes are DNA oligonucleotides that can undergo a specific chemical reaction in the presence o... more DNAzymes are DNA oligonucleotides that can undergo a specific chemical reaction in the presence of a cofactor. Ribonucleases are a specific form of DNAzymes where a tertiary structure undergoes cleavage at a single ribonuclease site. The cleavage is highly specificity to co-factors, which makes them excellent sensor recognition elements. Monitoring the change in structure upon cleavage has given rise to many sensing strategies; here we present a simple and rapid method of following the reaction using resistive pulse sensors, RPS. To demonstrate this methodology, we present a sensor for Ca2+ ions in solution. A nanoparticle was functionalised with a Ca2+ DNAzyme, and it was possible to follow the cleavage and rearrangement of the DNA as the particles translocate the RPS. The binding of Ca2+ caused a conformation change in the DNAzyme, which was monitored as a change in translocation speed. A 30 min assay produced a linear response for Ca2+ between 1–9 μm, and extending the incubation...

The pollution of heavy metal ions within the environmental is a global problem. The rapid and pre... more The pollution of heavy metal ions within the environmental is a global problem. The rapid and precise removal of these contaminants can be aided by identifying and quantifying the composition of the sample. It is therefore crucial to develop effective portable analytical techniques to determine the levels of heavy metal contamination. Paper-based analytical devices (PADs) offer a low cost method making them an excellent platform for onsite environmental sensors. Here we demonstrate how a PAD can be integrated into a multi-use Nanopore platform. The PAD was functionalised with different recognition ligands, who’s surface charge densities varied in the presence of an analyte. The surface of the PAD was placed in contact with a Nanopore which exhibited Ion Current Rectification (ICR). The extent of ICR, was dependent upon the PAD’s surface charge, and the presence of the analyte of interest i.e. the ICR phenomena was exaggerated or diminished indicating the presence of the metal ion in...

A universal aptamer-based sensing strategy is proposed using DNA modified nanocarriers and Resist... more A universal aptamer-based sensing strategy is proposed using DNA modified nanocarriers and Resistive Pulse Sensing for the rapid and label free detection of small molecules. The surface of a magnetic nanocarrier was first modified with a ssDNA aka linker which is designed to be partially complimentary in sequence to a ssDNA aptamer. The aptamer and linker form a stable dsDNA complex on the nanocarriers surface. Upon the addition of the target molecule, a conformational change takes place where the aptamer preferentially binds to the target over the linker; causing the aptamer to be released into solution. The RPS measures the change in velocity of the nanocarrier as its surface changes from dsDNA to ssDNA, and its velocity is used as a proxy for the concentration of the target. We illustrate the versatility of the assay by demonstrating the detection of the antibiotic Moxifloxacin, and chemotherapeutics Imatinib and Irinotecan.

Technologies that can detect and characterise particulates in liquids have applications in health... more Technologies that can detect and characterise particulates in liquids have applications in health, food and environmental monitoring. Here we present a low-cost and high-throughput multiuse counter that classifies a particle’s size, concentration, porosity and shape. Using an additive manufacturing process, we have assembled a reusable flow resistive pulse sensor. The device remains stable for several days with repeat measurements. We demonstrate its use for characterising algae with spherical and rod structures as well as microplastics shed from teabags. We present a methodology that results in a specific signal for microplastics, namely a conductive pulse, in contrast to particles with smooth surfaces such as calibration particles or algae, allowing the presence of microplastics to be easily confirmed and quantified. In addition, the shape of the signal and particle are correlated, giving an extra physical property to characterise suspended particulates. The technology can rapidly...

The Analyst

Nanoscale

The discovery and characterisation of nanomaterials represents a multidisciplinary problem, here ... more The discovery and characterisation of nanomaterials represents a multidisciplinary problem, here we apply predictive logistic regression models with resistive pulse sensing to create an rapid analysis technology.

Prion diseases are a group of fatal transmissible neurological conditions caused by the change in... more Prion diseases are a group of fatal transmissible neurological conditions caused by the change in conformation of the normal intrinsic cellular prion protein (PrPC) in to the highly ordered insoluble amyloid state conformer (PrPSC). We present a rapid assay using Aptamers and Resistive Pulse Sensing, RPS, to extract and quantify proteins from complex sample matrices, demonstrate with the quantification of PrPc. We functionalise the surface of superparamagnetic beads, SPBs, with a DNA aptamer. First SPB’s termed P-Beads, are used to pre-concentrate the analyte from a large sample volume. The PrPc protein is then eluted from the P-Beads before aptamer modified sensing beads, S-Beads, are added. The velocity of the S-Beads through the nanopore reveals the concentration of the PrPc protein. The process is done in under an hour and allows the detection of picomol’s of protein. The technique could be easily adopted to the mutated version of the protein and integrated into clinical workflo...

The use of nanocarriers within resistive pulse sensing, RPS, aids the detection and quantificatio... more The use of nanocarriers within resistive pulse sensing, RPS, aids the detection and quantification of analytes. In the absence of convection, the signal strength and frequency can dependent upon the electrophoretic mobility of the nanocarrier/ analyte. Here we have developed a simple strategy to incorporate peptide aptamers onto RPS assays with enhanced electrophoretic signals. Using a hybrid DNA-Peptide nanocarrier an existing peptide was incorporated into a rapid assay without having to engineer or modify the peptide sequence. The surface of a nanocarrier is coated with a mixture of peptide aptamers and a nonbinding DNA. The binding of the target to the peptide creates an “analyte corona” which shields the phosphate groups of the underlying DNA. This results in a change in electrophoretic mobility of the nanocarrier. The signal is concentration dependent and is illustrated using a peptide to a key biomarker of infection, C-Reactive Protein, CRP. As a comparison we also show the bi...

The interface between two immiscible liquids represent an ideal substrate for the assembly of nan... more The interface between two immiscible liquids represent an ideal substrate for the assembly of nanomaterials. The defect free surface provides a reproducible support for creating densely packed ordered materials. Here a droplet flow reactor is presented for the synthesis and/ or assembly of nanomaterials at the interface of the emulsion. Each droplet acts as microreactor for a reaction between decamethylferrocene (DmFc) within the hexane and metal salts (Ag+/ Pd2+) in the aqueous phase. The hypothesis was that a spontaneous, interfacial reaction would lead to the assembly of nanomaterials creating a Pickering emulsion. The subsequent removal of the solvents showed how the Ag nanoparticles were trapped at the interface and retain the shape of the droplet, however the Pd nanoparticles were dispersed with no tertiary structure. To further exploit this, a one-step process where the particles are synthesised and then assembled into core-shell materials was proposed. The same reactions wer...

Electrochimica Acta, Sep 1, 2003

Alumina membranes, with mean pore diameters of 100 nm, have been used as templates to control the... more Alumina membranes, with mean pore diameters of 100 nm, have been used as templates to control the electrodeposition of palladium. Deposition occurs at the polarised water–organic interface, leading to the formation of nanoparticles. The particles are formed at the mouth of the alumina pores, the locus of their formation being dictated by the position of the organic–water interface. It is shown that the relative position of the liquid phases with respect to the alumina is controlled by the surface wetting properties of the liquids, rather than gravity. ...

Abstract: A flow enhanced method and system for flow non-linear magnetophoresis (F-NLM) is descri... more Abstract: A flow enhanced method and system for flow non-linear magnetophoresis (F-NLM) is described. By tuning an external field frequency and the flow rate the migration velocities of different bead types may be caused to differ by several orders of magnitude over an extended range of frequencies to allow for separation of particles. Use of such efficiency in separation in bio-separation and similar assays is described.

Physical Chemistry Chemical Physics, 2005

Phys. Chem. Chem. Phys., Apr 8, 2005

This report discusses some specific mechanistic and structural factors that govern the deposition... more This report discusses some specific mechanistic and structural factors that govern the deposition of palladium and platinum from chloro-complexes at the electrified liquid/liquid interface. Factors studied here include: the age of the platinum solution, reactant depletion effects due to the formation of particles, and the previously noted phenomenon that the platinum particles created at the ITIES are smaller than their palladium counterparts, which is at variance with expectations based on the surface energies of the metals. A preliminary ...

Nanomedicine, 2016

An accurate characterization of nanomaterials used in clinical diagnosis and therapeutics is of p... more An accurate characterization of nanomaterials used in clinical diagnosis and therapeutics is of paramount importance to realize the full potential of nanotechnology in medicine and to avoid unexpected and potentially harmful toxic effects due to these materials. A number of technical modalities are currently in use to study the physical, chemical and biological properties of nanomaterials but they all have advantages and disadvantages. In this review, we discuss the potential of a relative newcomer, tunable resistive pulse sensing, for the characterization of nanomaterials and its applications in nanodiagnostics.

Faraday Discuss., 2016

We present the first comparison between assays that use resistive pulses or rectification ratios ... more We present the first comparison between assays that use resistive pulses or rectification ratios on a tunable pore platform. We compare their ability to quantify the cancer biomarker Vascular Endothelial Growth Factor (VEGF). The first assay measures the electrophoretic mobility of aptamer modified nanoparticles as they traverse the pore. By controlling the aptamer loading on the particle surface, and measuring the speed of each translocation event we are able to observe a change in velocity as low as 18 pM. A second non-particle assay exploits the current rectification properties of conical pores. We report the first use of Layer-by-Layer (LbL) assembly of polyelectrolytes onto the surface of the polyurethane pore. The current rectification ratios demonstrate the presence of the polymers, producing pH and ionic strength-dependent currents. The LbL assembly allows the facile immobilisation of DNA aptamers onto the pore allowing a specific dose response to VEGF. Monitoring changes to the current rectification allows for a rapid detection of 5 pM VEGF. Each assay format offers advantages in their setup and ease of preparation but comparable sensitivities.

The Analyst, 2016

In this review, recent advances in the development of electronic detection methodologies based on... more In this review, recent advances in the development of electronic detection methodologies based on non-antibody recognition elements such as functional liposomes, aptamers and synthetic peptides are discussed. Particularly, we highlight the progress of field effect transistor (FET) sensing platforms where possible as the number of publications on FET-based platforms has increased rapidly. Biosensors involving antibody-antigen interactions have been widely applied in diagnostics and healthcare in virtue of their superior selectivity and sensitivity, which can be attributed to their high binding affinity and extraordinary specificity, respectively. However, antibodies typically suffer from fragile and complicated functional structures, large molecular size and sophisticated preparation approaches (resource-intensive and time-consuming), resulting in limitations such as short shelf-life, insufficient stability and poor reproducibility. Recently, bio-sensing approaches based on synthetic elements have been intensively explored. In contrast to existing reports, this review provides a comprehensive overview of recent advances in the development of biosensors utilizing synthetic recognition elements and a detailed comparison of their assay performances. Therefore, this review would serve as a good summary of the efforts for the development of electronic bio-sensing approaches involving synthetic recognition elements.

Analytical chemistry, Jan 18, 2016

A novel approach for rapid and sensitive detection of matrilysin (MMP-7, a biomarker involved in ... more A novel approach for rapid and sensitive detection of matrilysin (MMP-7, a biomarker involved in the degradation of vari-ous macromolecules) based on polypeptide (JR2EC) functionalized reduced graphene oxide (rGO) field effect transistor (FET) is reported. MMP-7 specifically digests negatively charged JR2EC immobilized on rGO, thereby modulating the con-ductance of rGO-FET. The proposed assay enabled detection of MMP-7 at clinically relevant concentrations with a limit of detection (LOD) of 10 ng/mL (400 pM), attributed to the significant reduction of the net charge of JR2EC upon digestion by MMP-7. Quantitative detection of MMP-7 in human plasma was further demonstrated with a LOD of 40 ng/mL, illustrating the potential for the proposed methodology for tumor detection and carcinoma diagnostic (e.g. lung cancer and salivary gland cancer). Additionally, excellent specificity of the proposed assay was demonstrated using matrix metallopeptidase 1 (MMP-1), a protease of the same family....