Highly Integrated Centrifugal Microfluidic Chips And Their Applications

Microfluidics has been the focus of academic and industrial studies in the past few decades.With people's increasing demanding of health care,microfluidics has crushed in the picture for its low cost,portability and high-throughput.It deals with the behaviour,precise control and manipulation of fluids that are geometrically constrained to a small,typically sub-millimeter,scale.Until now,many common biological tests,including whole blood processing,nuclear acid amplification(PCR),immunoassays(ELISA),colorimetric detection of biomarkers,the analysis of food and water and so on,have been implemented on microfluidic chips successfully.However,as the increasing extending of microfluidic applications,the control of the fluids on microfluidic chips has been more complexed.First,many biological applications need multiple groups of tests,which means complex handy works for microfluidics.The precision and efficiency of those tests can be influenced since those tests can be hard to react at the same time.Besides,many chips can be monomorphic,they can not integrate complex bioassays which has multiple steps,limiting the application extension and development of microfluidics.Among those common microfluidic technologies,centrifugal microfluidics,or lab-on-a-disc(LOAD)has stood out for its various advantages compared to other microfluidic systems.The most important one is that all it needs is a compact motor to drive the fluid on the chip which won't bring much complex and extra redundancy to the chip design.No more manual operations is needed as it may influence the fluidic process sometimes if the acting force is not uniform.For centrifugal microfluidics,all one need is a motor and set the rotating speed or acceleration.What's more,without those extra tubes or pumps setting on the microfluidic devices,many complex bioassays with sequential process can be integrated on one disc.Since the centrifugal microfluidic chip or discs can be mass produced using polycarbonate and other cheap materials,it can be used as disposable devices for its low cost.Centrifugal pump doesn't rely on the physicochemical properties of the fluid such as PH or ionic strength,so that many kind of fluidic can be pumped on the centrifugal microfluidic platform including blood or urine and other biological fluids.Based on the LOAD platform,this article proposed a spiral main channel based chip for real-time parallel automated protein calibration.10 assays were integrated on the chip and ten group of reagents with the same volume can be metered quickly based on the spiral main channel.Compared to other metering structure this one showed higher time and process efficiency and the sequential reactions can be realized simultaneously.Our unique spiral based chip has demonstrated its high integration and brief logical operations and its automated feature has cut off much artificial work.The ten assays can be finished within quite a short time and can combined with the inline absorption detection method to finish the automated real-time detection function.Based on the traditional LOAD platform,we also proposed a binary centrifugal microfluidic platform.For traditional chip on LOAD,it always has one state and monomorphic function,the centrifugal force from center to outside has always been the focus of the disc design.Based on this,this article brought up an idea of binary centrifugal microfluidic platform that owns two states:LEFT and RIGHT.It utilized the other parameter that can be adjusted in centrifugal microfluidics besides rotating speed,the acceleration,to switch the state by acceleration induced Euler force.The two states and switching ability makes chip design much flexible,many other fluidic operations that requires complex structures and microfluidic networks can be simplified.The periodical switching of state would provide a "clock" signal for sequence of droplet binary logic operations.With the binary states platform and the "clock" signal,the binary chip would become organized and reliable,the sequential process would be very clear.Besides,it also makes the chip design isolated from the LOAD platform,so as the chip design and the platform.Thus the binary platform can match multiple chips with different functionality.Based on the binary platform,we again made design of these unit operations based on the proposed binary microfluidics platform.The unit operation consist of valving,mixing,metering,flow switching and droplet generation.Then we implement the common preset step of many biology assays and molecular diagnosis assay,protein calibration and DNA purification on binary platform to put it into practical use.The design of the chip has combined the inspiration of the structure of the unit operation and is unique based on the feature of our platform,the flow control all goes well and is very stable and reliable.In this article we made a specific comparison and analysis of the outcome on the disc or chip with the standard kit process,not only the results in our chip can be well comparable with the kit process,but also the chips have achieved high efficiency,low time cost and simple handling,indicating the success of those integrated applications on both platforms and the flexibility of the design.The chips we designed in this article can integrate those complex bioassays onto a single chip,and the logic control is very clear,the whole process can be very fast.Those chips not only has high expansibility and integration,but also performs quite the same with the standard kit process.Those works can lay a function for the subsequent product realization.