The application of detrended fluctuation analysis to assess physical characteristics of the human cell line ECV304 following toxic challenges

© 2019 In this paper we present a non-contact, impedance-based sensor system capable of characterizing the toxic response of cells to three different types of toxin. ECV304 cells were treated with 1 mM Hydrogen peroxide, 5% Dimethyl Sulfoxide, and 10 μg/ml saponin. Impedance spectroscopy was performed over a 2 h period on the cells within a commercial cell growth chamber, positioned on a pair of measurement electrodes, at frequencies between 200 and 830 kHz at 10 kHz intervals. Analysis of the impedance data was undertaken using the feature-extraction technique, Detrended Fluctuation Analysis (DFA). DFA scales the autocorrelation of a non-stationary signal, such as those generated using impedance spectroscopy for cytotoxicity testing. The correlation between the average fluctuation of the signal, F(n) (and scaling exponent, α) and a measurement of the cell size from image analysis was evaluated. The results showed that F(n) and α were strongly related to the changes of the morphological size of the cells. The results demonstrated that non-contact impedance spectroscopy, coupled with DFA can be used to monitor cell size in real time

Metal oxide decorated carbon nanocomposite electrodes for propofol monitoring

Despite the growing evidence of the benefits of total-intravenous anaesthesia using propofol compared to conventional volatile-based anaesthesia, both in terms of environmental impact and patient outcomes, the majority of administered general anaesthetics use volatile agents. A significant reason for this is the lack of suitablemethods for continuous, real-time propofol monitoring. Here we present a cytochrome P450 2B6/carbon nanotube/graphene oxide/metal oxide nanocomposite sensor for propofol monitoring. The enzyme prevents electrode fouling by converting the propofol into a quinone/quinol redox pair and the nanocomposite enables rapid and sensitive detection. The nanocomposite was synthesised via a simple ‘green synthesis’-based approach using an extract of common bay laurel. It was found that composites containing iron oxide nanoparticles resulted in the best performance, with a limit of detection of 7.0 ± 0.7 ng/ml and a sensitivity of 29.9 ± 6.4 nA/μg/ml/mm2. The sensor demonstrated good specificity with respect to several common perioperative drugs, propofol detection was demonstrated in a ‘serum-like’ solution and produced a linear response across the therapeutic range of propofol (1–10 μg/ml)

Propofol detection for monitoring of intravenous anaesthesia: A review

This paper presents a review of established and emerging methods for detecting and quantifying the intravenous anaesthetic propofol in solution. There is growing evidence of numerous advantages of total intravenous anaesthesia using propofol compared to conventional volatile-based anaesthesia, both in terms of patient outcomes and environmental impact. However, volatile-based anaesthesia still accounts for the vast majority of administered general anaesthetics, largely due to a lack of techniques for real-time monitoring of patient blood propofol concentration. Herein, propofol detection techniques that have been developed to date are reviewed alongside a discussion of remaining challenges

Mathematical modelling of a magnetic immunoassay

© The authors 2017. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved. A mathematical model is developed to describe the action of a novel form of fluidic biosensor that uses paramagnetic particles (PMPs) that have been pre-coated with target-specific antibodies. In an initial phase the particles are introduced to a sample solution containing the target which then binds to the particles via antigen-antibody reactions. During the test phase a magnet is used to draw the PMPs to the sensor surface which is similarly coated with specific antibodies. During this process, cross-links are formed by the antigens thereby binding the PMPs to the sensor surface. After the magnetic field is removed, a voltage change across an inductor below the sensor surface is recorded, which is deemed to depend on the number of magnetic particles that have been bound to the sensor surface. The fundamental question addressed is to explain the range of experimentally observed dose-response curves, and how this depends on the various parameters of the problem. In particular, observations have shown both rising and falling dose-response curves, as well as 'hooked' dose-response curves possessing local maxima. Initially a particle-dynamics computational model is produced to determine the time scales of the key processes involved, but is shown to be unable to produce differently shaped dose-response curves. The computational model suggests spatio-temporal effects are unimportant, therefore a homogenized rateequation model is developed for each of the key phases of the immunoassay process. Binding rates are shown to depend on various geometric factors related to the diameter of the PMPs and the size of the sensor surface. The dose-response is shown to depend crucially on various saturation effects during each phase, and conditions can be derived, in some cases analytically, for each of the three qualitatively different curve types. Furthermore, non-dimensionalization reveals 5 key dimensionless parameters and the dependence of these curve shapes on each is revealed. The results point to future quantitative approaches to sensor design and calibration

Nanoparticle-based 3D membrane for impedimetric biosensor applications

This paper reports on a comparison between nano-ZnO/CuO and nano-ZnO nitrocellulose membrane biosensors, both of which were fabricated using a simple and inexpensive sonication technique. To produce the nano-ZnO/CuO membranes, the technique involved sonication of 1% (w/v) ZnO and 1% (w/v) CuO nano-crystal colloidal suspensions, with a volume ratio of 1:2. The membranes were analysed by scanning electron microscopy and energy-dispersive spectroscopy, which showed the gradated distribution of nanoparticles in the membrane. Impedance spectroscopy demonstrated that the sonication resulted in a greater than two-fold enhancement of the output signal. Changes in impedance phase values, at a frequency of 100 Hz, were used to establish dose dependent responses for C-reactive protein (CRP). Limits of detection of 27 pg/mL for the 1% (w/v) nano-ZnO and 16 pg/mL for the 1% (w/v) nano-ZnO/CuO nitrocellulose membrane biosensors were demonstrated

An electrochemical screen-printed sensor based on gold-nanoparticle-decorated reduced graphene oxide–carbon nanotubes composites for the determination of 17-β estradiol

In this study, a screen-printed electrode (SPE) modified with gold-nanoparticle-decorated reduced graphene oxide–carbon nanotubes (rGO-AuNPs/CNT/SPE) was used for the determination of estradiol (E2). The AuNPs were produced through an eco-friendly method utilising plant extract, eliminating the need for severe chemicals, and remove the requirements of sophisticated fabrication methods and tedious procedures. In addition, rGO-AuNP serves as a dispersant for the CNT to improve the dispersion stability of CNTs. The composite material, rGO-AuNPs/CNT, underwent characterisation through scanning electron microscopy (SEM), ultraviolet–visible absorption spectroscopy (UV–vis), Fourier-transform infrared (FTIR) spectroscopy, and atomic force microscopy (AFM). The electrochemical performance of the modified SPE for estradiol oxidation was characterised using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The rGO-AuNPs/CNT/SPE exhibited a notable improvement compared to bare/SPE and GO-CNT/SPE, as evidenced by the relative peak currents. Additionally, we employed a baseline correction algorithm to accurately adjust the sensor response while eliminating extraneous background components that are typically present in voltammetric experiments. The optimised estradiol sensor offers linear sensitivity from 0.05–1.00 µM, with a detection limit of 3 nM based on three times the standard deviation (3δ). Notably, this sensing approach yields stable, repeatable, and reproducible outcomes. Assessment of drinking water samples indicated an average recovery rate of 97.5% for samples enriched with E2 at concentrations as low as 0.5 µM%, accompanied by only a modest coefficient of variation (%CV) value of 2.7%

Modeling peptide nucleic acid binding enthalpies using MM-GBSA

The binding enthalpies of peptide nucleic acid (PNA) homoduplexes were predicted using a molecular mechanics generalized Born surface area approach. Using the nucleic acid nearest-neighbor model, these were decomposed into sequence parameters which could replicate the enthalpies from thermal melting experiments with a mean error of 8.7%. These results present the first systematic computational investigation into the relationship between sequence and binding energy for PNA homoduplexes and identified a stabilizing helix initiation enthalpy not observed for nucleic acids with phosphoribose backbones

Initial trail results of a magnetic biosensor for the rapid detection of Porcine Reproductive and Respiratory Virus (PRRSV) infection

© 2019 The resonant coil magnetometer quantifies paramagnetic particles (PMPs) and has been used to develop magneto-immunoassays in a range of formats. The advantage of magneto-immunoassays is that they are relatively inexpensive, portable, easy to perform and give results in under 5 min. Porcine Reproductive and Respiratory Virus (PRRSV) is an infection of domesticated pigs producing large economic losses in the swine industry current diagnosis is performed using commercially available ELISA kits. Here we describe the development of a competitive magneto-immunoassay (MIA) and pilot study with porcine serum samples. The data show that this technology has the potential for use as a rapid and portable in field system for the detection of antibodies in porcine serum to PRRSV. A range of assay parameters and magnetometer settings were optimised, including the concentration of antibody conjugated PMPs used in the assay and movement of an external magnet to pull particles to a sensor surface. PRRSV positive control serum demonstrated competition with antibody conjugated PMPs with a dose dependent relationship. The magneto-immunoassay developed showed good agreement with the PRRS IDEXX X3 ELISA. The PRRSV magneto-immunoassay demonstrated a sensitivity of 73% and specificity of 100%. The results suggest that a rapid assay using the magnetometer technology detects specific anti-PRRSV antibody in pig serum. The magneto-immunoassay is suitable for use as a rapid ‘on-site’ method for the serological detection of PRRSV infection

Passive impedance sensing using a SAW resonator-coupled biosensor for zero-power wearable applications

A bio-sensing scheme, which acquires impedance information of a capacitive biosensor by using the reflected RF signal from a surface acoustic wave (SAW) resonator connected to the biosensor, is proposed. This technique requires no power to be supplied to the biosensor node and hence is highly applicable to wearable applications. Theoretical analysis has demonstrated that the sensitivity of the SAW resonator-coupled biosensor is higher than that of traditional impedance loaded SAW sensors and therefore it is more suitable for measuring the very small impedance changes in biosensors. The passive detection of the change in the impedance of a capacitive biosensor, as a result of biological binding events associated with the capture of a target analyte, has been demonstrated by preliminary experimentation. Dry tests of the SAW coupled capacitive biosensor using a cable connected network analyzer showed the aF level capacitance measurement resolution, which was only achieved in transistor level circuits previously, could be attained. When liquid samples with concentrations of C-Reactive Protein (CRP) in the range of 0.1 to 2 μg/ml were applied to the biosensor, a corresponding change in the resonant frequency of the SAW resonator-coupled biosensor (in the order of sub-hundred kHz) was observed. This has demonstrated the potential for applying this technique in applications where a zero-power requirement at the biosensor node could be a distinct advantage, when the cable link between the network analyzer and the biosensor node is replaced by the RF transmission

Modelling a dynamic magneto-agglutination bioassay

The process of developing an end-to-end model of a magneto-immunoassay is described which models the agglutination effect due to specific binding of bacteria to paramagnetic particles. After establishing the properties of the dose-specific agglutination through direct imaging, a microfluidic assay was used to demonstrate changes in the magnetophoretic transport dynamics of agglutinated clusters via transient inductive magentometer measurements. End-to-end mathematical modelling is used to establish the physical processes underlying the assay. First, a modification form of Becker–Döring nucleation kinetic equations is used to establish a relationship between analyte dose and average cluster size. Next, Stokes flow equations are used to establish a relationship between cluster size and speed of motion within the fluid chamber. This predicts a cluster-size dynamic profile of concentration of PMPs versus time when the magnetic field is switched between the two actuated magnets. Finally, inductive modelling is carried out to predict the response of the magnetometer circuit in response to this dynamics of magnetic clusters. The predictions of this model is shown to agree well with the results of experiments, and to predict the shape of the dose-response curve