Electrical and Electronic Engineering - Research Publications
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ItemDesign and Optimisation of Elliptical-Shaped Planar Hall Sensor for Biomedical Applications(MDPI, 2022-02)The magnetic beads detection-based immunoassay, also called magneto-immunoassay, has potential applications in point-of-care testing (POCT) due to its unique advantage of minimal background interference from the biological sample and associated reagents. While magnetic field detection technologies are well established for numerous applications in the military, as well as in geology, archaeology, mining, spacecraft, and mobile phones, adaptation into magneto-immunoassay is yet to be explored. The magnetic field biosensors under development tend to be multilayered and require an expensive fabrication process. A low-cost and affordable biosensing platform is required for an effective point-of-care diagnosis in a resource-limited environment. Therefore, we evaluated a single-layered magnetic biosensor in this study to overcome this limitation. The shape-induced magnetic anisotropy-based planar hall effect sensor was recently developed to detect a low-level magnetic field, but was not explored for medical application. In this study, the elliptical-shaped planar hall effect (EPHE) sensor was designed, fabricated, characterized, and optimized for the magneto-immunoassay, specifically. Nine sensor variants were designed and fabricated. A customized measurement setup incorporating a lock-in amplifier was used to quantify 4.5 µm magnetic beads in a droplet. The result indicated that the single-domain behaviour of the magnetic film and larger sensing area with a thinner magnetic film had the highest sensitivity. The developed sensor was tested with a range of magnetic bead concentrations, demonstrating a limit of detection of 200 beads/μL. The sensor performance encourages employing magneto-immunoassay towards developing a low-cost POCT device in the future.
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ItemLetter: improved parsimony of genetic risk scores for coeliac disease through refined HLA modelling(WILEY, 2021-03)LINKED CONTENT This article is linked to Sharp et al paper. To view this article, visit https://doi.org/10.1111/apt.15826
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ItemMeander Thin-Film Biosensor Fabrication to Investigate the Influence of Structural Parameters on the Magneto-Impedance Effect(MDPI, 2021-10)Thin-film magneto-impedance (MI) biosensors have attracted significant attention due to their high sensitivity and easy miniaturization. However, further improvement is required to detect weak biomagnetic signals. Here, we report a meander thin-film biosensor preparation to investigate the fabrication parameters influencing the MI effect. Specifically, we hypothesized that an optimal film thickness and sensing area size ratio could be achieved to obtain a maximum MI ratio. A meander multilayer MI biosensor based on a NiFe/Cu/NiFe thin-film was designed and fabricated into 3-, 6-, and 9-turn models with film thicknesses of 3 µm and 6 µm. The 9-turn biosensor resembled the largest sensing area, while the 3- and 6-turn biosensors were designed with identical sensing areas. The results indicated that the NiFe film thickness of 6 µm with a sensing area size of 14.4 mm2 resembling a 9-turn MI biosensor is the optimal ratio yielding the maximum MI ratio of 238%, which is 70% larger than the 3- and 6-turn structures. The 3- and 6-turn MI biosensors exhibited similar characteristics where the MI ratio peaked at a similar value. Our results suggest that the MI ratio can be increased by increasing the sensing area size and film thickness rather than the number of turns. We showed that an optimal film thickness to sensing area size ratio is required to obtain a high MI ratio. Our findings will be useful for designing highly sensitive MI biosensors capable of detecting low biomagnetic signals.
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ItemNovel features for capturing temporal variations of rhythmic limb movement to distinguish convulsive epileptic and psychogenic nonepileptic seizures(WILEY, 2019-01)OBJECTIVE: To investigate the characteristics of motor manifestation during convulsive epileptic and psychogenic nonepileptic seizures (PNES), captured using a wrist-worn accelerometer (ACM) device. The main goal was to find quantitative ACM features that can differentiate between convulsive epileptic and convulsive PNES. METHODS: In this study, motor data were recorded using wrist-worn ACM-based devices. A total of 83 clinical events were recorded: 39 generalized tonic-clonic seizures (GTCS) from 12 patients with epilepsy, and 44 convulsive PNES from 7 patients (one patient had both GTCS and PNES). The temporal variations in the ACM traces corresponding to 39 GTCS and 44 convulsive PNES events were extracted using Poincaré maps. Two new indices-tonic index (TI) and dispersion decay index (DDI)-were used to quantify the Poincaré-derived temporal variations for every GTCS and convulsive PNES event. RESULTS: The TI and DDI of Poincaré-derived temporal variations for GTCS events were higher in comparison to convulsive PNES events (P < 0.001). The onset and the subsiding patterns captured by TI and DDI differentiated between epileptic and convulsive nonepileptic seizures. An automated classifier built using TI and DDI of Poincaré-derived temporal variations could correctly differentiate 42 (sensitivity: 95.45%) of 44 convulsive PNES events and 37 (specificity: 94.87%) of 39 GTCS events. A blinded review of the Poincaré-derived temporal variations in GTCS and convulsive PNES by epileptologists differentiated 26 (sensitivity: 70.27%) of 44 PNES events and 33 (specificity: 86.84%) of 39 GTCS events correctly. SIGNIFICANCE: In addition to quantifying the motor manifestation mechanism of GTCS and convulsive PNES, the proposed approach also has diagnostic significance. The new ACM features incorporate clinical characteristics of GTCS and PNES, thus providing an accurate, low-cost, and practical alternative to differential diagnosis of PNES.
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ItemHeater Integrated Lab-on-a-Chip Device for Rapid HLA Alleles Amplification towards Prevention of Drug Hypersensitivity(MDPI, 2021-05)HLA-B*15:02 screening before administering carbamazepine is recommended to prevent life-threatening hypersensitivity. However, the unavailability of a point-of-care device impedes this screening process. Our research group previously developed a two-step HLA-B*15:02 detection technique utilizing loop-mediated isothermal amplification (LAMP) on the tube, which requires two-stage device development to translate into a portable platform. Here, we report a heater-integrated lab-on-a-chip device for the LAMP amplification, which can rapidly detect HLA-B alleles colorimetrically. A gold-patterned micro-sized heater was integrated into a 3D-printed chip, allowing microfluidic pumping, valving, and incubation. The performance of the chip was tested with color dye. Then LAMP assay was conducted with human genomic DNA samples of known HLA-B genotypes in the LAMP-chip parallel with the tube assay. The LAMP-on-chip results showed a complete match with the LAMP-on-tube assay, demonstrating the detection system's concurrence.
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ItemA Label-Free, Quantitative Fecal Hemoglobin Detection Platform for Colorectal Cancer Screening(MDPI, 2017-06)The early detection of colorectal cancer is vital for disease management and patient survival. Fecal hemoglobin detection is a widely-adopted method for screening and early diagnosis. Fecal Immunochemical Test (FIT) is favored over the older generation chemical based Fecal Occult Blood Test (FOBT) as it does not require dietary or drug restrictions, and is specific to human blood from the lower digestive tract. To date, no quantitative FIT platforms are available for use in the point-of-care setting. Here, we report proof of principle data of a novel low cost quantitative fecal immunochemical-based biosensor platform that may be further developed into a point-of-care test in low-resource settings. The label-free prototype has a lower limit of detection (LOD) of 10 µg hemoglobin per gram (Hb/g) of feces, comparable to that of conventional laboratory based quantitative FIT diagnostic systems.
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ItemMagneto-Impedance Biosensor Sensitivity: Effect and Enhancement(MDPI, 2020-09)Biosensors based on magneto-impedance (MI) effect are powerful tools for biomedical applications as they are highly sensitive, stable, exhibit fast response, small in size, and have low hysteresis and power consumption. However, the performance of these biosensors is influenced by a variety of factors, including the design, geometry, materials and fabrication procedures. Other less appreciated factors influencing the MI effect include measuring circuit implementation, the material used for construction, geometry of the thin film sensing element, and patterning shapes compatible with the interface microelectronic circuitry. The type magnetic (ferrofluid, Dynabeads, and nanoparticles) and size of the particles, the magnetic particle concentration, magnetic field strength and stray magnetic fields can also affect the sensor sensitivity. Based on these considerations it is proposed that ideal MI biosensor sensitivity could be achieved when the sensor is constructed in sandwich thick magnetic layers with large sensing area in a meander shape, measured with circuitry that provides the lowest possible external inductance at high frequencies, enclosed by a protective layer between magnetic particles and sensing element, and perpendicularly magnetized when detecting high-concentration of magnetic particles.
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ItemUltrasensitive and label-free biosensor for the detection of Plasmodium falciparum histidine-rich protein II in saliva.(Nature Publishing Group, 2019-11-25)Malaria elimination is a global public health priority. To fulfil the demands of elimination diagnostics, we have developed an interdigitated electrode sensor platform targeting the Plasmodium falciparum Histidine Rich Protein 2 (PfHRP2) protein in saliva samples. A protocol for frequency-specific PfHRP2 detection in phosphate buffered saline was developed, yielding a sensitivity of 2.5 pg/mL based on change in impedance magnitude of the sensor. This protocol was adapted and optimized for use in saliva with a sensitivity of 25 pg/mL based on change in resistance. Further validation demonstrated detection in saliva spiked with PfHRP2 from clinical isolates in 8 of 11 samples. With a turnaround time of ~2 hours, the label-free platform based on impedance sensors has the potential for miniaturization into a point-of-care diagnostic device for malaria elimination.
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ItemThe utility of an automated and ambulatory device for detecting and differentiating epileptic and psychogenic non-epileptic seizures.(Wiley-Blackwell Publishing, Inc., 2019-06)Objective: Accurate differentiation between epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) can be challenging based on history alone. Inpatient video EEG monitoring (VEM) is often needed for a definitive diagnosis. However, VEM is highly resource intensive, is of limited availability, and cannot be undertaken over long periods. Previous research has shown that time-frequency analysis of accelerometer data could be utilized to differentiate between ES and PNES. Using a seizure detection and classification algorithm, we sought to examine the diagnostic utility of an automated analysis with an ambulatory accelerometer. Methods: A wrist-worn device was used to collect accelerometer data from patients during VEM admission, for diagnostic evaluation of convulsive seizures. An automated process, that involved the use of K-means clustering and support vector machines, was used to detect and classify each seizure as ES or PNES. The results were compared with VEM diagnoses determined by epileptologists blinded to the accelerometer data. Results: Twenty-four convulsive seizures, consisting of at least 20 seconds of sustained continuous activity, recorded from 11 patients during inpatient VEM (13 PNES from five patients and 11 ES from six patients) were included for analysis. The automated system detected all convulsive seizures (ES, PNES) from >661 hours of recording with 67 false alarms (2.4 per 24 hours). The sensitivity and specificity for classifying ES from PNES were 72.7% and 100%, respectively. The positive and negative predictive values for classifying PNES were 81.3% and 100%, respectively. There was no significant difference between the classification results obtained from the automation process and the VEM diagnoses. Significance: This automated system can potentially provide a wearable out-of-hospital seizure diagnostic monitoring system.
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ItemRapid Detection of HLA-B*57:01-Expressing Cells Using a Label-Free Interdigitated Electrode Biosensor Platform for Prevention of Abacavir Hypersensitivity in HIV Treatment(MDPI AG, 2019-08-20)Pre-treatment screening of individuals for human leukocyte antigens (HLA) HLA-B*57:01 is recommended for the prevention of life-threatening hypersensitivity reactions to abacavir, a drug widely prescribed for HIV treatment. However, the implementation of screening in clinical practice is hindered by the slow turnaround time and high cost of conventional HLA genotyping methods. We have developed a biosensor platform using interdigitated electrode (IDE) functionalized with a monoclonal antibody to detect cells expressing HLA-B*57:01. This platform was evaluated using cell lines and peripheral blood mononuclear cells expressing different HLA-B alleles. The functionalized IDE sensor was able to specifically capture HLA-B*57:01 cells, resulting in a significant change in the impedance magnitude in 20 min. This IDE platform has the potential to be further developed to enable point-of-care HLA-B*57:01 screening