Mohd Ridzuan Ahmad
Non-Invasive Measurement Technique Based on Microfluidic Platform for Single Cell Analysis
Microelectromechanical system provides an excellent platform to perform single-cell analysis often known as lab-on-chip (LoC) microfluidic devices. LoC offers several advantages in single-cell analysis from the ability to manipulate small fluid volumes (µL, nL, pL) to provide efficient high throughput experimentation. However, depending on the analysis task that needs to be performed, microfluidic devices normally face two challenges, i.e. complex operational control and chip design. Our works have been focusing on developing simple yet functional microfluidic devices. The simplicity of the device is very important especially to the developing countries where there are limited resources and facilities. Furthermore, in terms of the manufacturing aspect, simple design can enable low-cost microfluidic devices. Our requirements for a simple microfluidic device are a single layer and a single channel. Based on these requirements, we have designed and fabricated several microfluidics devices for several single-cell analysis tasks. Here, we present three examples of our works in single-cell analysis, i.e. single-cell mass (SCM) determination, single-cell trapping, and single-cell sorting. Firstly, in SCM determination, drag force and Newton’s law of motion were used to determine the mass of single cells. This approach of measuring SCM was calibrated using known mass (77.3 pg) of a polystyrene particle of 5.2 diameters. Furthermore, we used Saccharomyces cerevisiae baker’s yeast cells of different sizes for SCM measurement. Mass of 4.4 diameters of single yeast cell was measured as 2.12 pg which is in the range of previously reported single yeast cell mass (2-3 pg). Besides, we also studied the relation between SCM and single-cell size. Results showed that single yeast cell mass increases exponentially with the increase of single-cell size. Secondly, in the single-cell trapping, a T-channel trapping chip was proposed to provide single-cell trapping and consequently could be a platform for cell treatments and manipulations. A demonstration for cell trapping in the T-channel model was presented in the simulation analysis and experimental work using HUVEC cell aggregate. The T-channel was found to be able to trap a single cell via the hydrodynamic resistance (Rh) concept using an appropriate channel geometry and RhMain/RhTrap ratio. Lastly, in single-cell sorting, we reported a tapered microfluidic device for passive continuous separation of microparticles by utilizing the hydrodynamic principle. By exploiting the hydrodynamic properties of the fluid flow and physical characteristics of microparticles, effective size-based separation was demonstrated. The tapered microfluidic device has widening geometries to a specific taper angle which amplifies the sedimentation effect experienced by particles of different sizes. A mixture of 3 μm and 15~20 μm polystyrene microbeads were successfully separated using 20° and 25° taper angles. The results obtained were in agreement with three-dimensional finite element simulation. Moreover, the feasibility of this mechanism for biological separation was demonstrated by using polydisperse samples consists of 3-μm polystyrene microbeads and human epithelial cervical carcinoma (HeLa) cells. 98% of the sample’s purity was recovered with a flow rate of 0.5 – 3.0 μl/min. We believe our works will be beneficial to enabling technology particularly in the point of care diagnosis tools.
Microfluidics, Single Cell Analysis, Non-Invasive Diagnosis
I obtained my Dr. Eng. (Micro-nano Systems Engineering) from Nagoya University, Japan in March 2010. I was a research officer in the Department of Robotics and Mechatronics, UTM, from June to November 2002. In 2003, I joined the Faculty of Electrical Engineering as a lecturer. I was promoted as a senior lecturer in 2011. Since 2011, I am a Principal Researcher at the Institute of Ibnu Sina, UTM and from 2014 as an Associate Researcher at the Advanced Photonics Science Institute in UTM. I was promoted to an Associate Professor in June 2017. In teaching, I have taught at the Faculty of Electrical Engineering, Universiti Teknologi Malaysia for fifteen years. I teach core and elective subjects that are related to the electrical engineering at the undergraduate and postgraduate levels. My research interests include multi-agent robotics system, micro/nanomanipulation, nanobiology, nanodevices, and single-cell analysis. I am a member of several professional engineering bodies such as the Institute of Electrical and Electronics Engineers (IEEE), Institute of Engineering and Technology (IET), a life member of Golden Key International Honor Society, a professional engineer of Board of Engineers Malaysia (BEM), a charted engineer of UK engineering council (IET) and a corporate member of Institute of Engineers Malaysia (IEM).