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  1. Thiha A, Ibrahim F
    Sensors (Basel), 2015;15(5):11431-41.
    PMID: 25993517 DOI: 10.3390/s150511431
    The enzyme-linked Immunosorbent Assay (ELISA) is the gold standard clinical diagnostic tool for the detection and quantification of protein biomarkers. However, conventional ELISA tests have drawbacks in their requirement of time, expensive equipment and expertise for operation. Hence, for the purpose of rapid, high throughput screening and point-of-care diagnosis, researchers are miniaturizing sandwich ELISA procedures on Lab-on-a-Chip and Lab-on-Compact Disc (LOCD) platforms. This paper presents a novel integrated device to detect and interpret the ELISA test results on a LOCD platform. The system applies absorption spectrophotometry to measure the absorbance (optical density) of the sample using a monochromatic light source and optical sensor. The device performs automated analysis of the results and presents absorbance values and diagnostic test results via a graphical display or via Bluetooth to a smartphone platform which also acts as controller of the device. The efficacy of the device was evaluated by performing dengue antibody IgG ELISA on 64 hospitalized patients suspected of dengue. The results demonstrate high accuracy of the device, with 95% sensitivity and 100% specificity in detection when compared with gold standard commercial ELISA microplate readers. This sensor platform represents a significant step towards establishing ELISA as a rapid, inexpensive and automatic testing method for the purpose of point-of-care-testing (POCT) in resource-limited settings.
  2. Thiha A, Ibrahim F, Muniandy S, Madou MJ
    Microsyst Nanoeng, 2019;5:62.
    PMID: 31754454 DOI: 10.1038/s41378-019-0103-0
    Carbon micro- and nanoelectrodes fabricated by carbon microelectromechanical systems (carbon MEMS) are increasingly used in various biosensors and supercapacitor applications. Surface modification of as-produced carbon electrodes with oxygen functional groups is sometimes necessary for biofunctionalization or to improve electrochemical properties. However, conventional surface treatment methods have a limited ability for selective targeting of parts of a surface area for surface modification without using complex photoresist masks. Here, we report microplasma direct writing as a simple, low-cost, and low-power technique for site-selective plasma patterning of carbon MEMS electrodes with oxygen functionalities. In microplasma direct writing, a high-voltage source generates a microplasma discharge between a microelectrode tip and a target surface held at atmospheric pressure. In our setup, water vapor acts as an ionic precursor for the carboxylation and hydroxylation of carbon surface atoms. Plasma direct writing increases the oxygen content of an SU-8-derived pyrolytic carbon surface from ~3 to 27% while reducing the carbon-to-oxygen ratio from 35 to 2.75. Specifically, a microplasma treatment increases the number of carbonyl, carboxylic, and hydroxyl functional groups with the largest increase observed for carboxylic functionalities. Furthermore, water microplasma direct writing improves the hydrophilicity and the electrochemical performance of carbon electrodes with a contact-angle change from ~90° to ~20°, a reduction in the anodic peak to cathodic peak separation from 0.5 V to 0.17 V, and a 5-fold increase in specific capacitance from 8.82 mF∙cm-2 to 46.64 mF∙cm-2. The plasma direct-writing technology provides an efficient and easy-to-implement method for the selective surface functionalization of carbon MEMS electrodes for electrochemical and biosensor applications.
  3. Thiha A, Ibrahim F, Muniandy S, Dinshaw IJ, Teh SJ, Thong KL, et al.
    Biosens Bioelectron, 2018 Jun 01;107:145-152.
    PMID: 29455024 DOI: 10.1016/j.bios.2018.02.024
    Nanowire sensors offer great potential as highly sensitive electrochemical and electronic biosensors because of their small size, high aspect ratios, and electronic properties. Nevertheless, the available methods to fabricate carbon nanowires in a controlled manner remain limited to expensive techniques. This paper presents a simple fabrication technique for sub-100 nm suspended carbon nanowire sensors by integrating electrospinning and photolithography techniques. Carbon Microelectromechanical Systems (C-MEMS) fabrication techniques allow fabrication of high aspect ratio carbon structures by patterning photoresist polymers into desired shapes and subsequent carbonization of resultant structures by pyrolysis. In our sensor platform, suspended nanowires were deposited by electrospinning while photolithography was used to fabricate support structures. We have achieved suspended carbon nanowires with sub-100 nm diameters in this study. The sensor platform was then integrated with a microfluidic chip to form a lab-on-chip device for label-free chemiresistive biosensing. We have investigated this nanoelectronics label-free biosensor's performance towards bacterial sensing by functionalization with Salmonella-specific aptamer probes. The device was tested with varying concentrations of Salmonella Typhimurium to evaluate sensitivity and various other bacteria to investigate specificity. The results showed that the sensor is highly specific and sensitive in detection of Salmonella with a detection limit of 10 CFU mL-1. Moreover, this proposed chemiresistive assay has a reduced turnaround time of 5 min and sample volume requirement of 5 µL which are much less than reported in the literature.
  4. Popović ŽV, Thiha A, Ibrahim F, Petrović BB, Dahlan NA, Milić L, et al.
    Sci Rep, 2023 Dec 02;13(1):21277.
    PMID: 38042878 DOI: 10.1038/s41598-023-48379-9
    Intraoral theranostics, the integration of diagnostics and therapeutics within the oral cavity, is gaining significant traction. This pioneering approach primarily addresses issues like xerostomia (dry mouth), commonly resulting from cancer treatment, with a specific focus on monitoring temperature and humidity. This paper introduces the innovative Intra-Oral Portable Micro-Electronic (IOPM) fluidic theranostic device platform. It leverages conventional dental spoons by incorporating advanced sensors for precise measurements of oral temperature and humidity. Personalization options include a microfluidic chip and a tooth model, enabling targeted delivery of therapeutic agents to optimize treatment outcomes. The electronic control system simplifies the administration of fluid dosages, intelligently adjusted based on real-time oral cavity temperature and humidity readings. Rigorous experimental evaluations validate the platform's precision in delivering fluid volumes at predefined intervals. This platform represents a transformative advancement for individuals contending with oral health challenges such as xerostomia (dry mouth). Furthermore, it has the potential to elevate oral healthcare standards by providing advanced diagnostics and tailored therapeutic solutions, benefiting both patients and dental professionals alike.
  5. Muniandy S, Teh SJ, Thong KL, Thiha A, Dinshaw IJ, Lai CW, et al.
    Crit Rev Anal Chem, 2019;49(6):510-533.
    PMID: 30648398 DOI: 10.1080/10408347.2018.1561243
    The development of easy to use, rapid and sensitive methods for direct detection of foodborne bacterial pathogens has become significantly important due to their impact on human health. In recent years, carbon nanomaterials have been adapted in the fabrication of electrochemical biosensors due to their exceptional combination of intrinsic properties such as high conductivity, stability and biocompatibility that render them as a promising candidate for bio-sensing material. The scope of this review is to provide a brief history of the current methods and different types of electrochemical biosensors used for the detection of bacterial pathogens. We primarily focus on the recent progress and applications of graphene, carbon nanotubes and their derivatives in electrochemical biosensors for foodborne bacterial pathogens detection. Finally, the status and future prospects of carbon-based electrochemical biosensors are also reviewed and discussed.
  6. Dahlan NA, Thiha A, Ibrahim F, Milić L, Muniandy S, Jamaluddin NF, et al.
    Nanomaterials (Basel), 2022 Nov 16;12(22).
    PMID: 36432311 DOI: 10.3390/nano12224025
    bioNEMS/MEMS has emerged as an innovative technology for the miniaturisation of biomedical devices with high precision and rapid processing since its first R&D breakthrough in the 1980s. To date, several organic including food waste derived nanomaterials and inorganic nanomaterials (e.g., carbon nanotubes, graphene, silica, gold, and magnetic nanoparticles) have steered the development of high-throughput and sensitive bioNEMS/MEMS-based biosensors, actuator systems, drug delivery systems and implantable/wearable sensors with desirable biomedical properties. Turning food waste into valuable nanomaterials is potential groundbreaking research in this growing field of bioMEMS/NEMS. This review aspires to communicate recent progress in organic and inorganic nanomaterials based bioNEMS/MEMS for biomedical applications, comprehensively discussing nanomaterials criteria and their prospects as ideal tools for biomedical devices. We discuss clinical applications for diagnostic, monitoring, and therapeutic applications as well as the technological potential for cell manipulation (i.e., sorting, separation, and patterning technology). In addition, current in vitro and in vivo assessments of promising nanomaterials-based biomedical devices will be discussed in this review. Finally, this review also looked at the most recent state-of-the-art knowledge on Internet of Things (IoT) applications such as nanosensors, nanoantennas, nanoprocessors, and nanobattery.
  7. Thiha A, Ibrahim F, Joseph K, Petrović B, Kojić S, Dahlan NA, et al.
    PLoS One, 2023;18(2):e0280381.
    PMID: 36795661 DOI: 10.1371/journal.pone.0280381
    Diagnosing oral diseases at an early stage may lead to better preventive treatments, thus reducing treatment burden and costs. This paper introduces a systematic design of a microfluidic compact disc (CD) consisting of six unique chambers that run simultaneously from sample loading, holding, mixing and analysis. In this study, the electrochemical property changes between real saliva and artificial saliva mixed with three different types of mouthwashes (i.e. chlorhexidine-, fluoride- and essential oil (Listerine)-based mouthwashes) were investigated using electrical impedance analysis. Given the diversity and complexity of patient's salivary samples, we investigated the electrochemical impedance property of healthy real saliva mixed with different types of mouthwashes to understand the different electrochemical property which could be a foundation for diagnosis and monitoring of oral diseases. On the other hand, electrochemical impedance property of artificial saliva, a commonly used moisturizing agent and lubricant for the treatment of xerostomia or dry mouth syndrome was also studied. The findings indicate that artificial saliva and fluoride-based mouthwash showed higher conductance values compared to real saliva and two other different types of mouthwashes. The ability of our new microfluidic CD platform to perform multiplex processes and detection of electrochemical property of different types of saliva and mouthwashes is a fundamental concept for future research on salivary theranostics using point-of-care microfluidic CD platform.
  8. Uddin SM, Ibrahim F, Sayad AA, Thiha A, Pei KX, Mohktar MS, et al.
    Sensors (Basel), 2015 Mar 05;15(3):5376-89.
    PMID: 25751077 DOI: 10.3390/s150305376
    In recent years, many improvements have been made in foodborne pathogen detection methods to reduce the impact of food contamination. Several rapid methods have been developed with biosensor devices to improve the way of performing pathogen detection. This paper presents an automated endpoint detection system for amplicons generated by loop mediated isothermal amplification (LAMP) on a microfluidic compact disk platform. The developed detection system utilizes a monochromatic ultraviolet (UV) emitter for excitation of fluorescent labeled LAMP amplicons and a color sensor to detect the emitted florescence from target. Then it processes the sensor output and displays the detection results on liquid crystal display (LCD). The sensitivity test has been performed with detection limit up to 2.5 × 10(-3) ng/µL with different DNA concentrations of Salmonella bacteria. This system allows a rapid and automatic endpoint detection which could lead to the development of a point-of-care diagnosis device for foodborne pathogens detection in a resource-limited environment.
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