Fabrication And Application Of High-throughput Microfluidic Platforms For The Synthesis Of Biomedical Materials

The first stage of material research and development is material design.The trial-and-error method,as a commonly used material design mode,has made significant contributions for the prosperity of material studies,however,its long R&D cycle and consuming of time and resources slows down the steps of materials development.The high-throughput experiments mode has thereby emerged aiming at providing massive data,shortening the R&D cycle,and accelerating the material design processes.Microfluidic technology has attracted widespread attention due to its low cost,small size,and high-throughput functions.This research designed two high-throughput synthesis platforms based on microfluidic technology and through building concentration gradient of the key reagents,a series of target products could be synthesized in single experiment.Biomedical materials calcium phosphates(Ca P)and nano-gold were chosen as the research objects and a series of micro/nano products with various of morphologies were synthesized and screened in a high-throughput manner.Below listed the main research contents:(1)Design and construction of flow-resistive high-throughput microfluidic synthesis platform and practical application explorationThe flow-resistive high-throughput microfluidic synthesis platform including core microarray chips with 9×9 microreactors array,a hydrogel concentration gradient generator,and a supporting device.And this platform could construct stable one-and two-dimensional concentration gradient by building a concentration difference in two sides of a dense hydrogel block,driven the fluid diffusing through the hydrogel block while building the concentration gradient and conduct 81 experiments in one single application.The practicability of the microfluidic platform was verified using Ca P as the research object.By manipulating the one-dimensional concentration gradients of p H,sodium citrate(Na₃Cit)and ethylenediaminetetraacetic acid disodium(Na₂EDTA)and establishing the two-dimensional gradients of p H and the calcium-phosphorus ratio(Ca/P),and p H and the citric acid-calcium ratio(Cit/Ca),a series of Ca P with various morphologies were synthesized in high-throughput manner.The scale-up experiments were conducted to evaluate the accuracy and reliability of the microfluidic platform screening results.The potential mechanism of p H,Ca/P and additive concentration to regulate the phase and morphology of Ca P products was analyzed and discussed.(2)Design and construction of volume-controlled high-throughput microfluidic synthetic platform and practical application explorationBased on the flow resistance microfluidic platform,a volume-controlled high-throughput microfluidic synthesis platform was designed to construct a concentration gradient by controlling the mixing volume of reagents.The platform contained two parts:microarray chips with 6×6 microreactors array and a supporting device,and this platform could generate a stable horizontal or orthogonal concentration gradient with calculable reaction conditions and conduct 36 experiments in parallel.The practicability and versatility of the designed platform were evaluated by taking nano-gold and Ca P as research objects.The morphology of nano-gold was manipulated by constructing a Na OH concentration gradient and the mechanism of the synthesis process and morphological change was discussed;and by constructing the Ca/P horizontal and orthogonal gradient,the structure of Ca P changed from flower-like structure to hydrangea shape and finally formed long strip structure,and by constructing a Na OH concentration gradient,flower-like Ca P with different assembly units was synthesized,and the potential mechanism of how Ca/P and Na OH concentration influenced the morphology of Ca P crystals was explored.And scale-up experiments were conducted to evaluate the accuracy and practicality of platform synthesis guiding batch synthesis.This study provided massive data for the screening of Ca P and nano-gold and the theoretical research.The designed microfluidic platforms are generic and could be applied to the research of other biomedical materials as screening tools providing valuable research results in a short time.Meanwhile,they can also help to enrich the material database,shorten the trial-and-error design cycle,and improve the efficiency of materials research and development while reducing the costs.