Design And Development Of POCT Devices Based On Digital Microfluidics

Purpose: Point-of-Care Testing(POCT)is a technology which is aimed at immediate medical diagnostic testing at the patient’s location,with the advantages of short turnaround time,easy operation without professional training of users,portability,intelligence,etc.It plays an important role in the field of in vitro diagnostics.Developing portable and efficient testing instruments meets the ongoing trend of POCT technology.Digital microfluidics(DMF)chip is a platform on which droplets function as micro-reaction vessels to carry fluids with micro-or nano-scale volumes,being programmably actuated by applying dielectric wetting-on-dielectrics(EWOD)with a control system,and are attractive to biochemical reaction analysisand thereby translational medicine.Compared with traditional laboratory assays,digital microfluidic chips have the advantages of low sample and reagent consumables,easy for automation,and zero dead volume,making them very suitable for POCT settings.The aim of this thesis is to design and establish a digital microfluidic chip-based device which meets POCT standards as many as possible.To achieve this,we designed and built each functional modules with a blocking-to-implement principle,followed by integrated assembling all the supporting hardware and software into a compact,completely self-contained and battery-powered case to automatically engage robust droplet maneuver,droplet status control,on-chip temperature control,and magnetic bead separation on the digital microfluidic chip.Methods: The related work in this device includes four parts: hardware system design,software system design,chip design,and housing design.In the hardware system design part,Altium Designer software was used to design the printed circuit board(PCB)of the main driver circuit,and a multimeter,oscilloscope,logic analyzer,signal generator and other equipment were used to debug the board for testing.The software system design includes two parts: the embedded software and the master computer software.Since the Arduino hardware development platform was chosen for this device,the embedded software program was scripted and burned into microcontrollers using the Arduino IDE,and the master computer software was developed using the Py Qt5 framework in a Python environment to realize the human to computer graph-user interface.The DMF chips used in this thesis,including the chromium-based digital microfluidic chip and the PCB-based digital microfluidic chip,were designed using a CAD software and Autium Designer software,respectively.And the chromium-based digital microfluidic chip was prepared using photolithography,in meanwhile the PCB-based digital microfluidic chip was rendered using standard printed circuit board process.To improve the robustness of droplet manipulation,modelling of the equivalent circuit was conducted on the DMF chip with droplets on it.Based on this model,measurement circuit,as well as the feedback control algorithm,of droplets was established accordingly.As a consequence,the introduction of liquid samples and the droplet manipulation were automatically engaged by a more robust closed loop control manner.In addition,in the housing design part,Solidworks software was used to design the overall housing and part of the fixtures of the instrument.Results: A digital microfluidic chip-based POCT device capable of all-in-one functions,such as feedback control engaged droplet driving and chip heating,as well as magnetic bead manipulation,was constructed.In this device,serial and parallel control of discrete droplets on the digital microfluidic was accomplished,and the full operations of droplets,including introduction,generation,transport,mixing and splitting,were reliably implemented.Other features of this device include: ? Portability and environmental adaptability of the device were promoted,assisted by a rechargeable lithium battery equipped in this device;? Micro-pumps were installed to automate sample feeding;? Impedance sensors were established to achieve real-time feedback on the droplet volume change and motion status on the digital microfluidic chip to improve the control of droplet generation volume and improve the reliability of droplet driving;? Precise temperature control was renderedwith a PID control algorithm;? Bead separation was achieved with a microcontroller-controlled spatial motor motion.Conclusion: In this thesis,a digital microfluidic chip-based and highly-integrated POCT device was designed,in which a power supply and its converter circuit,a driver circuit and other peripheral modules were established.The implementation of the feedback circuit provides the possibility for the device to drive droplets autonomously,minimizing the manual involvement.It provides a simpler and faster platform for medical personnel and other users in need to conduct tests on biochemical samples,such as nucleic acid amplification and detection experiments,and plays an important role in promoting the deployment of on-field testing.The developed device does not require an external power source and its size and weight meet the requirement of handheld instruments;In addition,this device may operate under either developer’s or user’s modes,and the latter mode renders self-contained operations engaged by embedded microcontrollers and does not need a master computer for system control.And this follows the comprehensive standard for a POCT device,such as affordable,user friendly,robust,easy to use and deliverable to end users.