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Numerous efforts have been undertaken to mitigate the Debye screening effect of FET biosensors for achieving higher sensitivity. There are few reports that show sub-femtomolar detection of biomolecules by FET mechanisms but they either suffer from significant background noise or lack robust control. In this aspect, deformed/crumpled graphene has been recently deployed by other researchers for various biomolecule detection like DNA, COVID-19 spike proteins and immunity markers like IL-6 at sub-femtomolar levels. However, the chemical vapor deposition (CVD) approach for graphene fabrication suffers from various surface contamination while the transfer process induces structural defects. In this paper, an alternative fabrication methodology has been proposed where glass substrate has been initially texturized by wet chemical etching through the sacrificial layer of synthesized silver nanoparticles, obtained by annealing of thin silver films leading to solid state dewetting. Graphene has been subsequently deposited by thermal reduction technique from graphene oxide solution. The resulting deformed graphene structure exhibits higher sensor response towards glial fibrillary acidic protein (GFAP) detection with respect to flat graphene owing to the combined effect of reduced Debye screening and higher surface area for receptor immobilization. Additionally, another interesting aspect of the reported work lies in the biomolecule capture by dielectrophoretic (DEP) transport on the crests of the convex surfaces of graphene in a coplanar gated topology structure which has resulted in 10 aM and 28 aM detection limits of GFAP in buffer and undiluted plasma respectively, within 15 min of application of analyte. The detection limit in buffer is almost four decades lower than that documented for GFAP using biosensors which is is expected to pave way for advancing graphene FET based sensors towards ultrasensitive point-of-care diagnosis of GFAP, a biomarker for traumatic brain injury. [ABSTRACT FROM AUTHOR]

Diverse efforts undertaken to mitigate the Debye screening effect of field-effect transistor (FET) biosensors have achieved higher sensitivity. However, the charge transfer or induction mechanism between the captured biomolecules and the sensing surface, resulting in shift of surface potential and, hence, the drain current magnitude, shows poor selectivity for real time detection of ultra-low biomolecule concentration in unamplified samples. Herein, enabling direct interaction of the target molecule with edge passivated thermally reduced graphene oxide, through the template of molecularly imprinted polymer (MIP), specific trap induced characteristic bulges in the noise spectrum has been observed only in the presence of target molecule. Such a phenomenon has not been observed either with antibodies or aptamers as receptors. Hence, the direct interface of MIP with a graphene FET (GFET) results in the generation of an additional electronic label in FET transduction. As a proof of concept, this principle has been validated for serotonin detection in serum in the presence of other neurotransmitters, resulting in detection limit of 0.05 fM in real time, which is more than two orders of magnitude lower than existing reports and, hence, is expected to pave the way for advancing GFET based sensors toward ultrasensitive point-of-care applications without requiring complex machine learning algorithms. [ABSTRACT FROM AUTHOR]

This article investigates the impact of incorporating silica nanoparticles of varying diameters in label free impedance immunosensor. It has been observed that even if the surface area improvement has been adjusted to be similar for all the diameters, the sensitivity is enhanced by five times at a particular diameter of 100 nm due to the optimum combination of intersection with electric field lines and surface convexity. This study has enabled the detection of 0.1 fM Hep-B surface antigen with a reliable sensitivity of around 75%. Further, it has been observed that the SNR corresponding to 0.1 fM is 20 dB only for 100 nm particle. This SNR is comparable to a recent report on Hep-B virus detection but the limit of detection in the proposed sensor is lowered by more than three orders of magnitude. [ABSTRACT FROM AUTHOR]

Oxidized porous silicon (PS) is a common topographical biocompatible substrate that potentially provides a distinct in vitro environment for better understanding of in vivo behavior. But in the reported studies on oxidized PS, cell-cell and cell-substrate interactions have been detected only by fluorescent labeling. This paper is the first attempt to investigate real-time sensing of these interactions on HaCaT cells by label-free impedance spectroscopy on oxidized PS of two pore diameters (50 and 500 nm). One of the major requirements for successful impedance spectroscopy measurement is to restrict the channeling of electric field lines through the pores. To satisfy this criterion, we have designed the pore depths after analyzing the penetration of the medium by using computational fluid dynamics simulation. A distributed electrical model was also developed for estimating the various cellular attributes by considering a pseudorandom distribution of pores. It is observed from the impedance measurements and from the model that the proliferation rate increases for 50 nm pores but decreases for 500 nm pores compared to that for planar substrates. The rate of decrease in cell substrate separation (h) in the initial stage is more than the rate of increase in cell-cell junction resistance (Rb) corresponding to the initial adhesion phase of cells. It is observed that Rb and h are higher for 50 nm pores than those for planar substrates, corresponding to the fact that substrates more conducive toward cell adhesion encourage cell-cell interactions than direct cell-substrate interactions. Thus, the impedance spectroscopy coupled with the proposed theoretical framework for PS substrates can sense and quantify the cellular interactions. [ABSTRACT FROM AUTHOR]

Recently, graphene nanogrid sensor has been reported to be capable of sub-femtomolar sensing of Hepatitis B (Hep-B) surface antigen in buffer. However, for such low concentration of Hep-B in serum, it has been observed during real-time operation that there is an overlap of around 50% in the drain–source current sensitivity values between different concentrations of the target biomolecule, in the range from 0.1 to 100 fM. This has been attributed to the fact that the concentration of non-specific antigen in serum being significantly higher than that of the target antigen, there is a considerable deviation in the number of captured target antigen for the same concentration. Further, this degree of overlap varies from one set to another set of sensor, depending on the statistical variations in the sensor fabrication process. This phenomenon challenges the quantification of target antigen for ultralow limit in physiological analyte. In this paper, we introduce probabilistic neural network (PNN) for quantification of Hep-B down to 0.1 fM in serum using graphene nanogrids field-effect transistor biosensor. The sensor has been operated in heterodyne mode in the frequency range of 100 kHz to 1 MHz applied between drain and source to overcome the problem of Debye screening effect. The application of PNN limits the quantification error within 10% in the range of 0.1 to 100 fM in contrast to 77% and 66% using polynomial fit and static neural network models, respectively. Further, the proposed methodology lowers the detection limit of Hep-B in serum by more than three orders of magnitude compared with the state-of-the-art, real-time, label-free sensors. [ABSTRACT FROM AUTHOR]

Reduced graphene oxide, in various configurations has been extensively researched as field effect transistor (FET) biosensor, but they usually exhibit low signal to noise ratio. In this paper, we report the fabrication of low noise FET biosensors with electrochemically reduced graphene oxide(ERGO) on fluorine doped tin oxide(FTO) glass, directly by electrochemical reduction of GO in solution. It has been observed that the sensor is capable of detecting down to1 fM concentration of Hep-B in serum with a dynamic range from 1 fM to 20 pM, linearity of around 95% and current sensitivity of 1.21 mA. Moreover, the signal to noise ratio is around 80 in serum, which is enhanced by more than one order of magnitude compared to the most sensitive reports. Further, the presence of Hep-B can be confirmed by the Lorentzian nature of noise spectra, which makes the detection more precise. The combined advantages of low cost and clean fabrication coupled with sensitive and reliable performance renders the device suitable for point of care diagnostics. [ABSTRACT FROM AUTHOR]

A smooth and reliable reduced graphene oxide (RGO) nanogrid structure has been developed using a nanoporous silicon oxide template, which resulted in the attomolar sensitivity of a field effect transistor biosensor. Scanning electron microscopy, Raman, surface profilometry, and conductance measurements verify the nanogrid structure of RGO, its bilayer thickness, and smoothness. The conductance of the biosensor reliably increases with the increasing concentration of hepatitis B virus molecules. The combined effects of insignificant line edges, quantum dot like transport behaviors, and improved interaction of the biomolecules within the nanopores with the pore walls have been attributed to the ultrasensitivity of the biosensor. [ABSTRACT FROM AUTHOR]

In this paper we demonstrate an efficient and non-interfering computational method for sub-femtomolar food toxin detection in complex mixture based on nanoporous silicon oxide impedance immunosensor by employing noise spectroscopy analysis at the peak frequency. It has been observed that the peak frequency ( f p ) values obtained from steady state impedance measurements cannot distinguish between solution with only the specific toxin, which is aflatoxin B1 (AfB1) and mixture of AfB1 with other non-specific toxins (NSTs), thus leading to erroneous quantification of AfB1 in complex mixture. On the other hand, the first cut-off frequency ( f c ) ranges obtained from noise spectroscopy analysis can qualitatively differentiate between solution containing only AfB1, AfB1 and NSTs and no AfB1. However f c values being very close for different concentration of AfB1 in pure solution and being overlapping for different mixtures cannot quantify AfB1 either in pure solution or in complex mixture. To address this problem, the proposed computational method first clusters the f p and f c values in 11 categories each using k -means clustering algorithm and then applies a simple combinational digital logic on the clusters of f p s and f c s to obtain the final output, realizable with standard NAND–NOR gates. The output digital word differs only with AfB1 concentration and not with concentration of NSTs and is found to be capable of detecting sub-femtomolar AfB1 range down to 0.1 fg/ml not only in pure solution but also in complex mixture with as high as 1000 ng/ml NSTs. This is the most sensitive and selective report so far on electrochemical food toxin immunosensors. [ABSTRACT FROM AUTHOR]

The use of porous silicon (PS) as an electrochemical biosensor has been reviewed. For electrochemical biosensing, the enhanced surface area is not the only advantage of using PS. In fact, depending on the transduction mechanisms, various issues like modulation of electric field lines through the pores and its interface with the biomolecules and ions of the analytes, nature of PS–metal contacts, orientation of the molecules within the pores and modification of the effective spring constant of the structure leading to a change in the resonant frequency have significant impact on sensitivity, reproducibility and longevity. In this review, we provide a critical assessment of the various factors which are actually responsible for enhanced performance of PS electrochemical biosensors. Formation procedures of PS for electrochemical biosensing have been mentioned. The mechanism of surface modification and derivatization has been briefly discussed. The contact formation techniques have been outlined. Four different categories of electrochemical biosensors using PS have been analysed in details with emphasis on equivalent circuit models and the specific role of PS in the electrical transduction mechanisms. Finally the existing challenges and the future prospects of such devices for commercial use are highlighted. [ABSTRACT FROM AUTHOR]

Most of the existing systems for elderly health monitoring deploy a large number of cognitive sensors including wearable sensors for physiological parameter measurement. Increasing number of sensors not only make the system power consuming and expensive but also intrusive in nature. However, there exists very limited research on power saving algorithms in such systems incorporating customer friendly features. In this paper, we report a modified health monitoring system which addresses both these issues. The central controller unit has an in-built algorithm based on two level adaptive branch prediction techniques to detect the period of inactivity of sensor nodes. Further, only one wearable heart rate sensor node is included in the system which measures the heart rate and detects abnormality. The central controller signals an alarm to the user to wear this predicting the sleeping time. This makes the system minimally intrusive and user friendly. Thus the multi-sensor network consists of motion sensor, current sensor and a wearable heart rate sensor along with a central controller unit. The prototype of the whole system has been installed in the house of elderly person and it has been observed that the time of prediction was close to the actual time for more than 90% of the days fo [ABSTRACT FROM AUTHOR]

Electric cell substrate impedance sensing has been widely used as a label free quantitative platform to study various cell biological processes and it is extremely essential to extract the parameters like the variation of the cell substrate spacing, changing projected area of the cell on the electrode and approximate cluster size during the non-confluent state to understand the mechanism of proliferation of the cells. The distributed analytical models developed so far to extract these parameters are applicable only under the conditions when the cells have become confluent. There are some lumped electrical models which have been reported for the non-confluent state but they do not provide correct estimate of the changing cell substrate spacing and the cell cluster size during growth. In this paper we develop extended distributed electrical models to characterize the impedance spectroscopy behavior of cultured HeLa cells in 200 Hz to 1 MHz range using eight well ECIS electrodes in the non-confluent state. The distributed model introduces some pseudo regularity in the arrangement of the non-confluent cells to extract the average ensemble of the significant parameters. The parameters extracted from the distributed model after 10 hours, 20 hours, and 30 hours of HeLa cell growth have been compared with the lumped circuit model and has been observed to fit the experimental data with a seven times improved fit quality factor. Further, the changing cell radius and cluster radius extracted at three different instants of time from the distributed analytical model have been found to match closely the microscopic observation in contrast to the lumped circuit model. [ABSTRACT FROM PUBLISHER]

We report an electrochemically fabricated silicon oxide nanoporous structure for ultrasensitive detection of AfB1 in food by shift in peak frequency corresponding to maximum sensitivity. It has been observed that the impedance sensitivity changes from 19% to 40% (which is only twice) where as the peak frequency shifts from 500 Hz to 50 kHz, for a change in concentration from 1 fg/ml to 1 pg/ml. This has been attributed to the combined effect of the significant pore narrowing with increasing AfB1 concentration and the opposing nature of impedance change within the nanopores and the conducting substrate immediately below the nanoporous layer. [ABSTRACT FROM AUTHOR]

This paper reports the optimization of electrode geometry on macroporous silicon biosensor for improved bacteria detection. Macroporous silicon of 8 μm thickness and 55% porosity has been fabricated on a 10-20 Ω-cm wafer using hydrofluoric acid and dimethyl sulfoxide. The electrode configurations selected for optimization are coplanar rectangular types with simple two-electrode, interdigitated comb finger-like electrode, and a combination of simple electrode and comb-shaped electrode designs. With these configurations, 14 different patterns have been generated with varying lengths and spacing within the technological constraints of low cost screen printing method of electrode fabrication with a wide range of effective exposed area from 0.04 to 0.6 mm2 by techniques from design of experiments. The sensitivity toward bacteria detection for all the patterns has been estimated by computation of an area utilization factor (AUF) which has been defined as the ratio of the effective area occupied by the captured bacteria to the effective exposed area available for capture. From the AUF values, eight patterns have been selected which are above a lower cut-off threshold for experimentation with E.coli O157 in the range of 102CFU/ml to 106 CFU/ml. It has been observed that the pattern with the highest AUF is capable of detecting 102CFU/ml E.coli O157 with a sensitivity of 11% without any pre-concentration which was not possible in the earlier reports of macroporous silicon. [ABSTRACT FROM PUBLISHER]

Abstract: Microimpedance affinity biosensors using interdigitated electrodes are being extensively employed for label free and rapid detection of bacteria molecules. To improve the sensitivity of such sensors, it is required to maximize the antibody immobilization and bacteria captured for an applied input concentration through proper quantification and also optimize the electrode geometry to achieve maximum signal to noise ratio. In this paper, a biomolecule compatible electrical model has been developed which quantifies the number of immobilized antibody and captured bacteria by simple calculations from impedance spectroscopy results which are comparable to the accuracy obtained by conventional time consuming and sometimes expensive biochemical methods and can also estimate the electrode impedance associated with each biomolecule. The model has been applied for the detection of Escherichia coli K12 bacteria by antibody–antigen binding method on gold electrodes with PBS as the background solution. The quantitative estimation of the actual number of antibody immobilized and bacteria captured for input concentration of 103 and 106 CFU/ml on the gold surface in this case has been matched with the conventional optical density methods and radioactive labeling method respectively. A quantitative relationship between the geometrical parameters and the output signal has been deduced after extracting the electrode impedance for each biomolecule and the effects of transducer geometry on the sensitivity of this biosensor have been matched with recently reported experimental results for the same system. Thus the proposed model enables quantitative estimation of the antibody immobilized and bacteria captured and quantitative prediction of the optimum geometry for maximum sensitivity eliminating the need for trial and error experimentation. This will lead to a rapid and cost effective method for performance enhancement of microimpedance biosensors with different topologies. [Copyright &y& Elsevier]

The authors would like to make corrections to the above paper [1, Fig. 2(b) and 4(b)] due to some post-processing carried out in these figures. After capturing the SEM image-cross-section [1, Fig. 2(b)], we wanted to measure the pore lengths, pore diameters at different positions along the lengths and also the spacing between the pores, to evaluate the uniformity of the electrochemical etching process. To do so, vertical and horizontal lines had to be constructed. For this purpose, we were trying to select different textured lines in the image processing software whose texture would match closely the original texture of the SEM image. But exact matching was not possible. Initially we tried to measure with a textured line, a part of which is actually the white region above the “nm” in 30 nm word in [1, Fig. 2(b)]. Later, we shifted to different textured lines which are visible above the “100 nm” word and also within the pores in [1, Fig. 2(b)]. Within the pores these lines look grayish. These lines are visible in most of the regions since they were a better match with the original SEM figure than the whitish line. However, all these lines were only for our own measurements and should have been deleted before submitting the final paper. [ABSTRACT FROM PUBLISHER]

The authors would like to make corrections to [1, Fig. 7(b) and (c)] due to some post-processing carried out in these figures. After capturing the SEM images—top view [Fig. 7(b)] and cross section [Fig. 7(c)] in [1], we started measuring the pore dimensions with image processing software. We wanted to measure both the lateral and the vertical diameters of the pores in Fig. 7(b) (since they are not exactly circular). For this purpose, a boundary was constructed around some of the pores with textured lines but mistakenly these lines were not removed during transferring the pictures to the manuscript, which is responsible for the distortion in [1, Fig. 7(b)]. In Fig. 7(c) also, we wanted to measure the pore length, for which textured lines were drawn along the length of the pore, leading to some changes in the color contrast at the mouth of the pore from the original SEM picture. These lines also should have been removed from [1, Fig. 7(c)]. [ABSTRACT FROM AUTHOR]

In this paper we report the sensing of aflatoxin B1(AFB1) by field effect capacitive method using electrophoretically deposited reduced graphene oxide (RGO) films for the first time. The RGO film has been characterized using SEM, surface profilometer and Raman spectroscopy. It has been observed that both quantum capacitance of RGO ( C q ) and effective electrical double layer capacitance ( C EDL ) contribute significantly towards the overall sensitivity for molar concentration in the range of 20–50 mM. As C q and C EDL changes in opposite direction after AFB1 capture and the nature of frequency dependence of C q and C EDL are different, the sensitivity shows a minima at a particular frequency. Interestingly, the sensitivity minima is also dependent on AFB1 concentration. Further, the maximum sensitivity obtained is around 30% for 10 −4 ppt (0.1 fg/ml) AFB1 which is greater than 1.5 times that of previous reports. This has been possible through the enhanced biomolecule immobilization capability of RGO. Thus the RGO based field effect capacitive sensor provides a combined advantage of both a high sensitivity and concentration dependent frequency behavior. [ABSTRACT FROM AUTHOR]

Abstract: Macroporous silicon is a promising material for wide spectrum of electrical applications ranging from photonic devices, microsystems engineering, supercapacitors to biosensors. Fabrication of good quality ohmic contact on macroporous silicon is a prerequisite for its widespread use in electrical sensor applications but it is also challenging since shallow nanopores are always present within the macropores. This paper aims at the formation of low resistance and fairly ohmic contacts on p-type macroporous silicon with 1.5μm pore diameter. Electrical contacts formed by vacuum evaporation of aluminium exhibit non-ohmic behaviour owing to the presence of the shallow nanoporous region formed on the surface of crystallites in macroporous silicon. To overcome this problem a controlled pre-annealing step at a temperature of 900°C for 30min leading to closure of shallow nanopores through coalescence of nanocrystallites of silicon due to grain growth has been carried out. The growth parameters are computed from the FESEM characteristics of the macroporous silicon preannealed at 900°C for varying time. For optimally preannealed macroporous silicon the I–V characteristics of macroporous silicon has been found to exhibit fairly ohmic behaviour with vacuum evaporated aluminium. Detailed electrical characterization of vacuum evaporated contacts on both unannealed and preannealed macroporous silicon has been carried out using modified TLM technique. It has been found that the specific contact resistance is almost five times lower for the latter. [Copyright &y& Elsevier]

• The impact of surface defects has been explored in terms of sensitivity. • Tuning of surface roughness and sensing of PSA have been done. • Transconductance of the sensors degrade monotonically with increasing defectdensity. • The optimized sensor has a PSA detection limit of 0.06 fM. • Nonoptimized sensor with initial detection limit of 0.1 fM has longevity of 4 months. In this work, the impact of surface defects in zinc oxide (ZnO) thin films on the performance of field effect transistor (FET) biosensors has been explored. Here, ZnO thin films have been fabricated using electron beam evaporation with various deposition parameters to tune the surface roughness and defect state density. The films have been deployed for sensing prostate specific antigen (PSA) after anti-PSA antibody immobilization. Interestingly, it has been observed that though the transconductance of the sensors degrade monotonically with increasing defect density, the antibody binding density has a non-monotonic behaviour due to enhanced steric hindrance effect beyond a certain limit of surface roughness. There is a variation of sensitivity by 15 times with different physical properties of ZnO and the optimized sensor has a PSA detection limit of 0.06 fM. Further, the sensor with the best sensitivity retains its performance upto 2 months while a non-optimized sensor with initial PSA detection limit of 0.1 fM has longevity of 4 months. Thus, it can be envisaged that tuning the surface defect state in ZnO FET biosensor is an essential requirement not only to ensure a low detection limit and high sensitivity but also to assure a reliable long term performance. [ABSTRACT FROM AUTHOR]

Ultrasensitive detection of serotonin is crucial for the early diagnosis of several diseases like Parkinson's and Alzheimer's. Most of the existing detection strategies are still not suitable for sensitive point-of-care applications. This study presents direct molecular imprinting of serotonin on the surface of three-dimensional zinc oxide (ZnO) nanorod devices connected in a field effect transistor (FET) configuration to achieve ultrasensitive, real-time, and rapid detection with a convenient and affordable approach, which has significant potential for translation to clinical settings. This strategy has enabled pushing the detection limit to 0.1 fM in a physiological analyte in real time with screen-printed electrodes, thereby resulting in the convenient batch fabrication of sensors for clinical validation. The response of the sensor with the clinical sample has been correlated with that of the gold standard and has been observed to be statistically similar.

To enable detection and discovery of biomarkers, development of label-free, ultrasensitive, and specific sensors is the need of the hour. For addressing this requirement, here, a Schottky-contacted ZnO nanorod biosensor has been demonstrated, which explores the interplay between Schottky junction capacitance and solution resistance, resulting in an interesting sensing principle of competitive impedance spectroscopy. When the transition of dominating impedance occurs from solution resistance to junction capacitance, a notch or a peak appears in the impedance response at a particular frequency (referred to as the corner frequency) depending on the charge of the target molecule. The appearance of the peak or notch acts like an electronic label for selectivity since it is visible only for target molecules even at ultralow concentrations in the physiological analyte, where the magnitude of impedance change overlaps with that for nonspecific molecules. This phenomenon has been successfully applied for the positively charged vascular endothelial growth factor (VEGF) and the negatively charged hepatitis B surface antigen (HBsAg), where the shifts in the higher corner frequencies for 1 aM concentration of the target molecules have been observed to be more than 3 times the changes in the impedance magnitude. Further, the area of the ZnO nanorods was segmented into two zones corresponding to the lower and higher concentration regimes, thereby expanding the dynamic range. To summarize, an ultralow detection limit of 1 aM with a dynamic range up to 1 pM was achieved for VEGF and HBsAg, which is 4 orders of magnitude and 20 times lower than their most sensitive label-free reports, respectively.

Solid-state nanopore has the ability to detect proteins at a single-molecule level with its high sensitivity, high-throughput, and low cost. Improvements in fabrication, functionalization, and characterization of solid-state nanopores keep evolving. Various analytical methods targeted towards diagnostic applications using nanopore-based devices are appearing. This review article provides an overview of recent progress in the field of solid-state and biological nanopores for protein detection in a complex analyte. The advantages and challenges involved in nanopore sensing have been discussed. Further, the review surpasses the steady-state resistive pulse techniques of sensing and incorporate transient variations in the nanopore conductance. Application of the power spectral density of these fluctuations toward sensing has been highlighted with importance on reducing the detection limit in a complex environment. Lastly, the current problems and future perspectives have been discussed with a perspective to increase nanopores performance towards diagnostic applications in complex medium., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Affordable point-of-care (PoC) diagnostic devices enable detection of prostate specific antigen (PSA) in resource limited settings. Despite the advancements in PoC systems, most of the reported methods for PSA detection have unsatisfactory detection limits and are based on labelled assays, requiring multiple reagent flow steps which increases both expenses and inconvenience. Circumventing these constraints, we report here the development and validation of a label free, affordable dielectrophoresis (DEP) based graphene field effect transistor (FET) sensor implemented using coplanar electrodes and integrated uniquely with a compact disc based microfluidic platform along with electronics readout for the estimation of PSA at the point of care. Design of coplanar gate electrode which has not been explored earlier is not a straightforward approach. In fact, it has been observed that there is a non-monotonic dependence of the capture of PSA molecules in the channel region of the FET with varying widths and spacings of the gate electrode. The graphene FET based PoC device with optimized coplanar gate electrode is the only label free analytical system for PSA detection requiring simple operation and achieving a detection limit of 1 pg/ml in serum with a wide dynamic range upto 4 ng/ml and appreciable selectivity against potential interferents like bovine serum albumin (BSA) and human immunoglobulin G (IgG). Further, it has been validated satisfactorily with commercially available existing systems using human serum samples. Moreover, the proposed sensing system lowers the detection limit by three orders of magnitude compared to a recent study on label free PoC device on other cancer biomarkers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An understanding of the current change in a solid state nanopore due to particle movement or capture is crucial for improvement of nanopore based sensing technologies. For lower aspect ratio pores, which are gaining importance due to their high sensitivity, there is interplay between access and pore resistance and the existing theories for computation of access resistance cannot explain most of the experimental observations. Hence, there is a need to develop a comprehensive model for calculating the effective conductance drop in presence of particles in a solid state nanopore. In this paper, we develop analytical models to calculate both the access and pore resistance in presence of particle at different positions during translocation and also when captured by receptors in functionalized nanopores. A wide range of pore geometry and molar strength has been investigated. Taking into consideration the positional uncertainty during particle translocation, the effective resistance sensitivity has been found to agree very well with the experimental observations in low aspect ratio pore. Additionally, we observe that in functionalized nanopores, a pore of higher diameter results in around 50% increase in sensitivity compared to a pore with half its diameter, which indicates the scope of design optimization in such systems.

Metabolic alterations of oral epithelial cells under oxidative stress are important signatures for early diagnosis of oral cancer. Amongst different metabolic alterations, non-invasive photo-diagnostic methods have been extensively used for determining cellular heme metabolism and accumulation of protoporphyrin IX (PpIX) under administration of suitable photosensitizer. In this study, we report these metabolic alterations by direct analysis of oral exfoliated cells obtained from individuals with prolonged smoking habit without the exogenous administration of any photosensitizer. The relative expression level of relevant biomolecules of study groups were compared with clinically diagnosed and histopathologically confirmed leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC) patients. The energy imbalance and variation in 'redox ratio' were examined through spectroscopic studies which showed an increasing trend (p < 0.001) in smokers to OSCC groups in comparison to nonsmoker control. Gene expression of important intermediates of the heme metabolic pathway (viz. 5-aminolevulinate synthase 1 (ALAS1), Ferrochelatase (FECH), hemeoxygenase 1 (HO-1) and ATP binding cassette subfamily G member 2 (ABCG2)) which affect production of PpIX was assessed. Relative mRNA level of ALAS1 and HO1 was upregulated whereas mRNA level of other genes (viz. FECH and ABCG2) were found to be downregulated in smokers as well as in cancer groups. Outcome of different spectroscopic studies on exfoliated cells (viz. fluorescence, atomic absorption and Fourier transform infrared spectroscopy) corroborated with the expression of biomarkers related to cellular endogenous metabolism related to heme cycle. This study indicates significant alterations in endogenous metabolic products, and cellular functional groups in oral epithelial cells among the study groups. Our study reports a strong possibility of diagnosis of early cancer signatures amongst habitual smokers by direct and non-invasive assessment of metabolic status of oral epithelial cells without exogenous administration of photosensitizers. The knowledge accrued from the study may guide clinicians in precise detection of precancer trend in the susceptible population through a noninvasive rapid screening method., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: This study aims to develop a novel noninvasive method for early cancer trend diagnosis in habitual smokers by corroborating cytomorphological and autofluorescence alterations., Materials & Methods: A total of 120 subjects were included and categorized into nonsmoker, smoker and clinically diagnosed oral potentially malignant disorder (OPMD) patients. Oral exfoliative epithelial cells were studied through differential interference contrast and fluorescence microscopy. Fuzzy trend analysis was performed using measured parameters for determining the risk factors among smokers., Results: The risk assessment in this study showed a positive correlation of smoking duration with early cancer risk factors with a correlation co-efficient of 0.86., Conclusion: Alterations in cellular morphology and autofluorescence intensities showed positive correlation with OPMD. The present study will benefit to investigate early prediction of OPMD among susceptible individuals.

Recently, a reproducible and scalable chemical method for fabrication of smooth graphene nanogrids has been reported which addresses the challenges of graphene nanoribbons (GNR). These nanogrids have been found to be capable of attomolar detection of biomolecules in field effect transistor (FET) mode. However, for detection of sub-femtomolar concentrations of target molecule in complex mixtures with reasonable accuracy, it is not sufficient to only explore the steady state sensitivities, but is also necessary to investigate the flicker noise which dominates at frequencies below 100 kHz. This low frequency noise is dependent on the exposure time of the graphene layer in the buffer solution and concentration of charged impurities at the surface. In this paper, the functionalization strategy of graphene nanogrids has been optimized with respect to concentration and incubation time of the cross linker for an enhancement in signal to noise ratio (SNR). It has been interestingly observed that as the sensitivity and noise power change at different rates with the functionalization parameters, SNR does not vary monotonically but is maximum corresponding to a particular parameter. The optimized parameter has improved the SNR by 50% which has enabled a detection of 0.05 fM Hep-B virus molecules with a sensitivity of around 30% and a standard deviation within 3%. Further, the SNR enhancement has resulted in improvement of quantification accuracy by five times and selectivity by two orders of magnitude., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

In this brief review, we summarize the recent research activities involved in the development of amperometric-type immunosensors based on screen-printed electrodes (SPEs). We focus on the underlying principle involved in these types of sensors, their fabrication and electrode surface modification. We also discuss the various factors involved in the designing of such immunosensors and how they affect their performances. Finally we provide an insight into the drawbacks associated with these SPEs.

Metal oxide semiconductors (MOS) are well known as reducing gas sensors. However, their selectivity and operating temperature have major limitations. Most of them show cross sensitivity and the operating temperatures are also relatively higher than the value reported here. To resolve these problems, here, we report the use of palladium-silver (70-30%) activated ZnO thin films as a highly selective methane sensor at low operating temperature (∼100 °C). Porous ZnO thin films were deposited on fluorine-doped tin oxide (FTO)-coated glass substrates by galvanic technique. X-ray diffraction showed polycrystalline nature of the films, whereas the morphological analyses (field emission scanning electron microscopy) showed flake like growth of the grains mainly on xy plane with high surface roughness (107 nm). Pd-Ag (70-30%) alloy was deposited on such ZnO films by e-beam evaporation technique with three different patterns, namely, random dots, ultrathin (∼1 nm) layer and thin (∼5 nm) layer as the activation layer. ZnO films with Pd-Ag dotted pattern were found show high selectivity towards methane (with respect to H2S and CO) and sensitivity (∼80%) at a comparatively low operating temperature of about 100°C. This type of sensor was found to have higher methane selectivity in comparison to other commercially available reducing gas sensor.

Re-epithelialization is one of the most important stages of cutaneous regeneration and its success requires supportive micro-ambience which may be provided with suitable bio-matrix. Biocompatibility and efficacy of such bio-matrix in re-epithelialization could be explored by multimodal analysis of structural and functional attributes of in vitro wound healing model including evaluation of prime molecular expressions of the epithelial cells during repair. Present study examines the influence of honey-alginate and alginate matrices on re-epithelialization in keratinocyte (HaCaT) population in a 2-D wound model. Cellular viability, proliferation and cell-cell adhesion status were assessed during wound closure using live/dead cell assay and by evaluating expressions of Ki67, p63 and E-cadherin along-with % change in cellular electrical impedance. Efficacy of honey-alginate matrix in comparison to only alginate one was demonstrated by a quicker reduction in wound gap, improved cellular viability, enhanced expressions of Ki67, p63 and its isoforms (TAp63, ΔNp63) as well as E-cadherin. Faster restoration of electrical attribute (% of impedance change) after wounding also indicated better impact of honey-alginate matrix in re-epithelialization., (Copyright © 2013 Elsevier B.V. All rights reserved.)