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  1. Khalili AA, Ahmad MR
    Int J Mol Sci, 2015;16(11):26770-85.
    PMID: 26569218 DOI: 10.3390/ijms161125987
    Single-cell analysis has become the interest of a wide range of biological and biomedical engineering research. It could provide precise information on individual cells, leading to important knowledge regarding human diseases. To perform single-cell analysis, it is crucial to isolate the individual cells before further manipulation is carried out. Recently, microfluidic biochips have been widely used for cell trapping and single cell analysis, such as mechanical and electrical detection. This work focuses on developing a finite element simulation model of single-cell trapping system for any types of cells or particles based on the hydrodynamic flow resistance (Rh) manipulations in the main channel and trap channel to achieve successful trapping. Analysis is carried out using finite element ABAQUS-FEA™ software. A guideline to design and optimize single-cell trapping model is proposed and the example of a thorough optimization analysis is carried out using a yeast cell model. The results show the finite element model is able to trap a single cell inside the fluidic environment. Fluid's velocity profile and streamline plots for successful and unsuccessful single yeast cell trapping are presented according to the hydrodynamic concept. The single-cell trapping model can be a significant important guideline in designing a new chip for biomedical applications.
  2. Mansor MA, Ahmad MR
    Int J Mol Sci, 2015;16(6):12686-712.
    PMID: 26053399 DOI: 10.3390/ijms160612686
    Electrical properties of living cells have been proven to play significant roles in understanding of various biological activities including disease progression both at the cellular and molecular levels. Since two decades ago, many researchers have developed tools to analyze the cell's electrical states especially in single cell analysis (SCA). In depth analysis and more fully described activities of cell differentiation and cancer can only be accomplished with single cell analysis. This growing interest was supported by the emergence of various microfluidic techniques to fulfill high precisions screening, reduced equipment cost and low analysis time for characterization of the single cell's electrical properties, as compared to classical bulky technique. This paper presents a historical review of single cell electrical properties analysis development from classical techniques to recent advances in microfluidic techniques. Technical details of the different microfluidic techniques are highlighted, and the advantages and limitations of various microfluidic devices are discussed.
  3. Khalili AA, Ahmad MR
    Int J Mol Sci, 2015 Aug 05;16(8):18149-84.
    PMID: 26251901 DOI: 10.3390/ijms160818149
    Cell adhesion is essential in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues. The mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. The essential function of cell adhesion has created tremendous interests in developing methods for measuring and studying cell adhesion properties. The study of cell adhesion could be categorized into cell adhesion attachment and detachment events. The study of cell adhesion has been widely explored via both events for many important purposes in cellular biology, biomedical, and engineering fields. Cell adhesion attachment and detachment events could be further grouped into the cell population and single cell approach. Various techniques to measure cell adhesion have been applied to many fields of study in order to gain understanding of cell signaling pathways, biomaterial studies for implantable sensors, artificial bone and tooth replacement, the development of tissue-on-a-chip and organ-on-a-chip in tissue engineering, the effects of biochemical treatments and environmental stimuli to the cell adhesion, the potential of drug treatments, cancer metastasis study, and the determination of the adhesion properties of normal and cancerous cells. This review discussed the overview of the available methods to study cell adhesion through attachment and detachment events.
  4. Bahari R, Mohamad Alwi MN, Ahmad MR, Mohd Saiboon I
    Malays Fam Physician, 2017;12(3):2-7.
    PMID: 29527273 MyJurnal
    Introduction: Motor vehicle accidents (MVAs) are daily occurrences in Malaysia but the extent to which victims are psychologically affected is not well known. The objective of this study is to determine the incidence and demographic characteristics of patients with post-traumatic stress disorder (PTSD) due to MVAs at a university hospital in Malaysia.

    Methods: Patients presenting to the emergency department from August to October 2014 due to MVA-related injuries were recruited. After a period of at least one month, they were followed-up and screened using the validated Malay Post Traumatic Stress Disorder Checklist Civilian version. A score of 30 was chosen as the cut-off point for PTSD.

    Results: In total, 112 patients presented to the emergency department following MVAs during the study period. Of these, 60.7% agreed for the follow-up. Among the respondents, the mean age was 26 years, 91.2% were males, 66.2% were married, 85.3% were Malays and 88.3% were Muslims. The calculated incidence of PTSD was 7.4%. There was no significant difference noted between the PTSD and non-PTSD groups.

    Conclusion: A considerable number of MVA victims in Malaysia may develop PTSD after the accident. Further research is needed to explore the factors that contribute or protect to develop the condition.

  5. Rad MA, Tijjani AS, Ahmad MR, Auwal SM
    Sensors (Basel), 2016 Dec 23;17(1).
    PMID: 28025571 DOI: 10.3390/s17010014
    This paper proposes a new technique for real-time single cell stiffness measurement using lead zirconate titanate (PZT)-integrated buckling nanoneedles. The PZT and the buckling part of the nanoneedle have been modelled and validated using the ABAQUS software. The two parts are integrated together to function as a single unit. After calibration, the stiffness, Young's modulus, Poisson's ratio and sensitivity of the PZT-integrated buckling nanoneedle have been determined to be 0.7100 N·m-1, 123.4700 GPa, 0.3000 and 0.0693 V·m·N-1, respectively. Three Saccharomyces cerevisiae cells have been modelled and validated based on compression tests. The average global stiffness and Young's modulus of the cells are determined to be 10.8867 ± 0.0094 N·m-1 and 110.7033 ± 0.0081 MPa, respectively. The nanoneedle and the cell have been assembled to measure the local stiffness of the single Saccharomyces cerevisiae cells The local stiffness, Young's modulus and PZT output voltage of the three different size Saccharomyces cerevisiae have been determined at different environmental conditions. We investigated that, at low temperature the stiffness value is low to adapt to the change in the environmental condition. As a result, Saccharomyces cerevisiae becomes vulnerable to viral and bacterial attacks. Therefore, the proposed technique will serve as a quick and accurate process to diagnose diseases at early stage in a cell for effective treatment.
  6. Mansor MA, Ahmad MR, Petrů M, Rahimian Koloor SS
    Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):371-383.
    PMID: 37548425 DOI: 10.1080/21691401.2023.2239274
    Electrical characteristics of living cells have been proven to reveal important details about their internal structure, charge distribution and composition changes in the cell membrane, as well as the extracellular context. An impedance flow cytometry is a common approach to determine the electrical properties of a cell, having the advantage of label-free and high throughput. However, the current techniques are complex and costly for the fabrication process. For that reason, we introduce an integrated dual microneedle-microchannel for single-cell detection and electrical properties extraction. The dual microneedles utilized a commercially available tungsten needle coated with parylene. When a single cell flows through the parallel-facing electrode configuration of the dual microneedle, the electrical impedance at multiple frequencies is measured. The impedance measurement demonstrated the differential of normal red blood cells (RBCs) with three different sizes of microbeads at low and high frequencies, 100 kHz and 2 MHz, respectively. An electrical equivalent circuit model (ECM) was used to determine the unique membrane capacitance of individual cells. The proposed technique demonstrated that the specific membrane capacitance of an RBC is 9.42 mF/m-2, with the regression coefficients, ρ at 0.9895. As a result, this device may potentially be used in developing countries for low-cost single-cell screening and detection.
  7. Balakrishnan SG, Ahmad MR, Koloor SSR, Petrů M
    J Adv Res, 2021 Nov;33:109-116.
    PMID: 34603782 DOI: 10.1016/j.jare.2021.03.001
    INTRODUCTION: Conventional biopsy, based on extraction from a tumor of a solid tissue specimen requiring needles, endoscopic devices, excision or surgery, is at risk of infection, internal bleeding or prolonged recovery. A non-invasive liquid biopsy is one of the greatest axiomatic consequences of the identification of circulating tumor DNA (ctDNA) as a replaceable surgical tumor bioQpsy technique. Most of the literature studies thus far presented ctDNA detection at almost final stage III or IV of cancer, where the treatment option or cancer management is nearly impossible for diagnosis.

    OBJECTIVE: Hence, this paper aims to present a simulation study of extraction and separation of ctDNA from the blood plasma of cancer patients of stage I and II by superparamagnetic (SPM) bead particles in a microfluidic platform for early and effective cancer detection.

    METHOD: The extraction of ctDNA is based on microfiltration of particle size to filter some impurities and thrombocytes plasma, while the separation of ctDNA is based on magnetic manipulation to high yield that can be used for the upstream process.

    RESULT: Based on the simulation results, an average of 5.7 ng of ctDNA was separated efficiently for every 10 µL blood plasma input and this can be used for early analysis of cancer management. The particle tracing module from COMSOL Multiphysics traced ctDNA with 65.57% of sensitivity and 95.38% of specificity.

    CONCLUSION: The findings demonstrate the ease of use and versatility of a microfluidics platform and SPM bead particles in clinical research related to the preparation of biological samples. As a sample preparation stage for early analysis and cancer diagnosis, the extraction and separation of ctDNA is most important, so precision medicine can be administered.

  8. Rosli AN, Ahmad MR, Alias Y, Zain SM, Lee VS, Woi PM
    J Mol Model, 2014 Dec;20(12):2533.
    PMID: 25433601 DOI: 10.1007/s00894-014-2533-9
    Design of neutral receptor molecules (ionophores) for beryllium(II) using unsaturated carbonitrile models has been carried out via density functional theory, G3, and G4 calculations. The first part of this work focuses on gas phase binding energies between beryllium(II) and 2-cyano butadiene (2-CN BD), 3-cyano propene (3-CN P), and simpler models with two separate fragments; acrylonitrile and ethylene. Interactions between beryllium(II) and cyano nitrogen and terminal olefin in the models have been examined in terms of geometrical changes, distribution of charge over the entire π-system, and rehybridization of vinyl carbon orbitals. NMR shieldings and vibrational frequencies probed charge centers and strength of interactions. The six-membered cyclic complexes have planar structures with the rehybridized carbon slightly out of plane (16° in 2-CN BD). G3 results show that in 2-CN BD complex participation of vinyl carbon further stabilizes the cyclic adduct by 16.3 kcal mol(-1), whereas, in simpler models, interaction between beryllium(II) and acetonitrile is favorable by 46.4 kcal mol(-1) compared with that of ethylene. The terminal vinyl carbon in 2-CN BD rehybridizes to sp (3) with an increase of 7 % of s character to allow interaction with beryllium(II). G4 calculations show that the Be(II) and 2-CN BD complex is more strongly bound than those with Mg(II) and Ca(II) by 98.5 and 139.2 kcal mol(-1) (-1), respectively. QST2 method shows that the cyclic and acyclic forms of Be(II)-2-CN BD complexes are separated by 12.3 kcal mol(-1) barrier height. Overlap population analysis reveals that Ca(II) can be discriminated based on its tendency to form ionic interaction with the receptor models.
  9. Woi PM, Bakar MA, Rosli AN, Lee VS, Ahmad MR, Zain S, et al.
    J Mol Model, 2014 May;20(5):2219.
    PMID: 24770548 DOI: 10.1007/s00894-014-2219-3
    DFT and G4 results reveal that cations display the following trends in imparting its positive charge to acrylonitrile; H⁺ > Li⁺ > Na⁺ > K⁺ for group I and Be²⁺ > Mg²⁺ > Ca²⁺ for group II. Solvation by water molecules and interaction with cation make the cyano bond more polarized and exhibits ketene-imine character. Bond order in nitrile-cation complexes has been predicted based on the s character of the covalent bond orbitals. Mulliken, CHELPG, and NPA charges are in good agreement in predicting positive charge buildup and GIAO nuclear deshileding on C1. G4 enthalpies show that Mg²⁺ is more strongly bound to acrylonitrile than to acetonitrile by 3 kcal mol⁻¹, and the proton affinity of the former is higher by 0.8 kcal mol⁻¹. G4 enthalpies of reductions support prior experimental observation that metalated conjugated nitriles show enhanced reactivity toward weak nucleophiles to afford Michael addition products.
  10. Ahmad MR, Nakajima M, Kojima M, Kojima S, Homma M, Fukuda T
    IEEE Trans Nanobioscience, 2012 Mar;11(1):70-8.
    PMID: 22275723 DOI: 10.1109/TNB.2011.2179809
    In this paper, single cells adhesion force was measured using a nanofork. The nanofork was used to pick up a single cell on a line array substrate inside an environmental scanning electron microscope (ESEM). The line array substrate was used to provide small gaps between the single cells and the substrate. Therefore, the nanofork could be inserted through these gaps in order to successfully pick up a single cell. Adhesion force was measured during the cell pick-up process from the deflection of the cantilever beam. The nanofork was fabricated using focused ion beam (FIB) etching process while the line array substrate was fabricated using nanoimprinting technology. As to investigate the effect of contact area on the strength of the adhesion force, two sizes of gap distance of line array substrate were used, i.e., 1 μm and 2 μm. Results showed that cells attached on the 1 μm gap line array substrate required more force to be released as compared to the cells attached on the 1 μm gap line array substrate.
  11. Ab Rahman S, Ahmed Shokri A, Ahmad MR, Ismail AF, Termizi NS
    Adv Orthop, 2020;2020:4539792.
    PMID: 32411483 DOI: 10.1155/2020/4539792
    Background: Implants used for total knee arthroplasty (TKA) in Asian patients are mostly produced based on anthropometry of the Western population, thus causing problem with patella sizing, especially in Asian females where the patellae are regarded to be smaller. This study is to define intraoperative patella dimensions in our female populations and compare them with current prosthetic systems available at our institution.

    Methods: This is a cross-sectional study involving 156 TKA female patients with normal patellae. The patella height, width, thickness, medial and lateral articular facets' width and thickness, and the dome position were measured. The smallest implant size from 3 manufacturers was compared to the data obtained. Analysis using descriptive statistics was used to get the mean and median of anatomical patella dimensions, whereas the independent T test and one-way ANOVA test were used to compare the Malaysian female's patella dimensions with various implant sizes.

    Results: The articular surface of the patella was found to have an oval shape with a width-height ratio of 1.31. The mean (SD) patella thickness, width, and height were 20.7 (1.85) mm, 40.7 (3.79) mm, and 31.3 (2.81) mm, respectively. Only 17.9% fit for smallest implant size from all 3 manufacturers. The oval-shape implant was suitable in 53.8% patients based on their width-height ratio. The dome position is 2.2 mm medial to centre.

    Conclusion: These female patients have thinner and smaller patella, which are generally unable to accommodate patellar components based on the Caucasian database. Therefore, orthopaedic implant manufacturers should consider optimizing the thicknesses as well as widths of their patellar prostheses.

  12. Rad MA, Ahmad MR, Nakajima M, Kojima S, Homma M, Fukuda T
    Scanning, 2017;2017:8393578.
    PMID: 29109826 DOI: 10.1155/2017/8393578
    The preparation and observations of spheroplast W303 cells are described with Environmental Scanning Electron Microscope (ESEM). The spheroplasting conversion was successfully confirmed qualitatively, by the evaluation of the morphological change between the normal W303 cells and the spheroplast W303 cells, and quantitatively, by determining the spheroplast conversion percentage based on the OD800 absorbance data. From the optical microscope observations as expected, the normal cells had an oval shape whereas spheroplast cells resemble a spherical shape. This was also confirmed under four different mediums, that is, yeast peptone-dextrose (YPD), sterile water, sorbitol-EDTA-sodium citrate buffer (SCE), and sorbitol-Tris-Hcl-CaCl2 (CaS). It was also observed that the SCE and CaS mediums had a higher number of spheroplast cells as compared to the YPD and sterile water mediums. The OD800 absorbance data also showed that the whole W303 cells were fully converted to the spheroplast cells after about 15 minutes. The observations of the normal and the spheroplast W303 cells were then performed under an environmental scanning electron microscope (ESEM). The normal cells showed a smooth cell surface whereas the spheroplast cells had a bleb-like surface after the loss of its integrity when removing the cell wall.
  13. Zahoor F, Hussin FA, Khanday FA, Ahmad MR, Mohd Nawi I
    Micromachines (Basel), 2021 Oct 21;12(11).
    PMID: 34832702 DOI: 10.3390/mi12111288
    Due to the difficulties associated with scaling of silicon transistors, various technologies beyond binary logic processing are actively being investigated. Ternary logic circuit implementation with carbon nanotube field effect transistors (CNTFETs) and resistive random access memory (RRAM) integration is considered as a possible technology option. CNTFETs are currently being preferred for implementing ternary circuits due to their desirable multiple threshold voltage and geometry-dependent properties, whereas the RRAM is used due to its multilevel cell capability which enables storage of multiple resistance states within a single cell. This article presents the 2-trit arithmetic logic unit (ALU) design using CNTFETs and RRAM as the design elements. The proposed ALU incorporates a transmission gate block, a function select block, and various ternary function processing modules. The ALU design optimization is achieved by introducing a controlled ternary adder-subtractor module instead of separate adder and subtractor circuits. The simulations are analyzed and validated using Synopsis HSPICE simulation software with standard 32 nm CNTFET technology under different operating conditions (supply voltages) to test the robustness of the designs. The simulation results indicate that the proposed CNTFET-RRAM integration enables the compact circuit realization with good robustness. Moreover, due to the addition of RRAM as circuit element, the proposed ALU has the advantage of non-volatility.
  14. Rosli AN, Abu Bakar MA, Lee VS, Zain SM, Ahmad MR, Abdul Manan NS, et al.
    J Mol Model, 2014 Sep;20(9):2428.
    PMID: 25149440 DOI: 10.1007/s00894-014-2428-9
    In this work, hybrid functional and G4 methods were employed in the rational design of carbonitrile-carboxaldehyde receptor models for cation recognition. Electron-sharing and ionic interactions between the models and the cations were analyzed utilizing the concepts of overlap population, atomic valence, electrostatic potential, and CHELPG charge in order to elucidate the nature of the heteroatom-metal interaction, the N versus O disparity, and the effect of pH. Receptor fragment models from ionomycin were employed to rationalize the selection of receptor models for discriminating group I cations and enhancing the selectivity for Mg(II) rather than Ca(II), and to examine the effects of keto-enol forms and negatively charged sites. The changes in geometries, overlap population, metal valence, and CHELPG charge upon solvation in heptane medium as compared to the gas phase were negligible. The optimized geometries reveal that the interaction between group II cations and the keto, enol, and enolate forms of 2-cyanoethanal causes 12 % bending of the C-C-N angle from linearity. Overlap populations show that the electron-sharing interaction favors group II cations but that the same mechanism allows Li(I) to compete. The total spin of Li(I) is 17 % greater than that of Ca(II), but the G4 binding energies of the two are separated by more than 50 kcal/mol, favoring group II cations, which may eliminate interference from Li(I). 1,2-Dicyanoethylene, which has only one form, shows similar characteristics. CHELPG analysis shows that Mg(II) transfers 25 and 18 % of its positive charge to 2-cyanoethanal enolate and 1,2-dicyanoethylene, respectively. Hydrogen atoms receive most of the positive charge in both receptors, but the N-termini exhibit strikingly different characteristics. Electrostatic potential contour profiles were found to be in good agreement with the atomic charge distributions. The application of uncharged 1,3-dicarbonyl and 2-cyanocarbonyl receptors and a judicious choice of polymeric membrane that suppresses the Hofmeister effect should lead to high selectivity for magnesium, whereas the utilization of multiple negatively charged ionophores should result in selectivity for calcium.
  15. Mohd Saiboon I, Jaafar MJ, Ahmad NS, Nasarudin NM, Mohamad N, Ahmad MR, et al.
    Med Teach, 2014 Mar;36(3):245-50.
    PMID: 24295218 DOI: 10.3109/0142159X.2013.857013
    Self-instruction video (SIV) has been widely explored as a teaching mode for cardiopulmonary resuscitation (CPR) and automated external defibrillation (AED), but not with other basic emergency skills.
  16. Rosli AN, Bakar MA, Manan NS, Woi PM, Lee VS, Zain SM, et al.
    Sensors (Basel), 2013;13(10):13835-60.
    PMID: 24129020 DOI: 10.3390/s131013835
    Combined computational and experimental strategies for the systematic design of chemical sensor arrays using carbonitrile neutral receptors are presented. Binding energies of acetonitrile, n-pentylcarbonitrile and malononitrile with Ca(II), Mg(II), Be(II) and H⁺ have been investigated with the B3LYP, G3, CBS-QB3, G4 and MQZVP methods, showing a general trend H⁺ > Be(II) > Mg(II) > Ca(II). Hydrogen bonding, donor-acceptor and cation-lone pair electron simple models were employed in evaluating the performance of computational methods. Mg(II) is bound to acetonitrile in water by 12.5 kcal/mol, and in the gas phase the receptor is more strongly bound by 33.3 kcal/mol to Mg(II) compared to Ca(II). Interaction of bound cations with carbonitrile reduces the energies of the MOs involved in the proposed σ-p conjugated network. The planar malononitrile-Be(II) complex possibly involves a π-network with a cationic methylene carbon. Fabricated potentiometric chemical sensors show distinct signal patterns that can be exploited in sensor array applications.
  17. Al-Khaleefa AS, Ahmad MR, Isa AAM, Esa MRM, Aljeroudi Y, Jubair MA, et al.
    Sensors (Basel), 2019 May 25;19(10).
    PMID: 31130657 DOI: 10.3390/s19102397
    Wi-Fi has shown enormous potential for indoor localization because of its wide utilization and availability. Enabling the use of Wi-Fi for indoor localization necessitates the construction of a fingerprint and the adoption of a learning algorithm. The goal is to enable the use of the fingerprint in training the classifiers for predicting locations. Existing models of machine learning Wi-Fi-based localization are brought from machine learning and modified to accommodate for practical aspects that occur in indoor localization. The performance of these models varies depending on their effectiveness in handling and/or considering specific characteristics and the nature of indoor localization behavior. One common behavior in the indoor navigation of people is its cyclic dynamic nature. To the best of our knowledge, no existing machine learning model for Wi-Fi indoor localization exploits cyclic dynamic behavior for improving localization prediction. This study modifies the widely popular online sequential extreme learning machine (OSELM) to exploit cyclic dynamic behavior for achieving improved localization results. Our new model is called knowledge preserving OSELM (KP-OSELM). Experimental results conducted on the two popular datasets TampereU and UJIndoorLoc conclude that KP-OSELM outperforms benchmark models in terms of accuracy and stability. The last achieved accuracy was 92.74% for TampereU and 72.99% for UJIndoorLoc.
  18. Ba Hashwan SS, Khir MHM, Nawi IM, Ahmad MR, Hanif M, Zahoor F, et al.
    Nanoscale Res Lett, 2023 Feb 27;18(1):25.
    PMID: 36847870 DOI: 10.1186/s11671-023-03779-8
    Piezoelectric microelectromechanical system (piezo-MEMS)-based mass sensors including the piezoelectric microcantilevers, surface acoustic waves (SAW), quartz crystal microbalance (QCM), piezoelectric micromachined ultrasonic transducer (PMUT), and film bulk acoustic wave resonators (FBAR) are highlighted as suitable candidates for highly sensitive gas detection application. This paper presents the piezo-MEMS gas sensors' characteristics such as their miniaturized structure, the capability of integration with readout circuit, and fabrication feasibility using multiuser technologies. The development of the piezoelectric MEMS gas sensors is investigated for the application of low-level concentration gas molecules detection. In this work, the various types of gas sensors based on piezoelectricity are investigated extensively including their operating principle, besides their material parameters as well as the critical design parameters, the device structures, and their sensing materials including the polymers, carbon, metal-organic framework, and graphene.
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