Automated Silicon Microfluidics Platform for Controlling and Analyzing Chemical Reactions with Applications in Compartmentalized Synthesis and Chemical Computing

Abstract

Traditional chemical synthesis is performed in batch, requiring bulky glass ware and large quantities of reagents while offering only limited control over the reaction conditions, mixing or sample extraction. To vary reaction conditions and/or reagents, the entire procedure must be restarted from scratch, glass ware cleaned etc. which results in an inefficient and labor-intensive procedure. Recently, robotic systems enabled some chemical actions to be automated, ranging from dispensing of reagents to handling of vials for sample extraction, thereby offering means to automatically perform more systematic and parametric reaction screenings with the precision of a machine - not being subject to human handling variations. Additionally, chemical reaction compartments with in- and outlet ports and internal mixing functionalities can be operated in a flow configuration. This enables a high degree of automation as the reactor can be seamlessly integrated in the chemical workflow and compounds can be fed from syringe- or pressure-based pumps supplied from large reservoirs to facilitate extensive screening campaigns. Such automated systems can further be equipped with a variety of online analytical methods, which may provide almost immediate feedback of reaction yields that can again be fed back into the design of experiments to efficiently probe multiple reaction space configurations. In such automated or even autonomously operated synthesis platforms, the type of reactor is a key component. It defines the mixing, the mass-flow conditions, the concentration gradients and the dwell time as well as all environmental conditions of the reaction, which includes, for instance, the temperature, the electrochemical potentials, the illumination properties for photochemical processes etc. Furthermore, some reactors can further be directly functionalized with online analytics, such as optical windows for transmission experiments for UV-Vis, Raman or infrared spectroscopy, electrodes for electrical impedance spectroscopy, cyclic voltammograms etc. We present a solid-state platform for creating such multi-purpose reactors which allows for scalable reaction volumes ranging from tens of µl down to 1 nl due to the use of enhanced semiconductor fabrication technologies. The high solvent compatibility of pristine or functionalized silicon combined with is high mechanical compliance, the ultrafast heat transfer and no diffusion of oxygen through the silicon corpus provides means for high-precision synthesis with most efficient triggers and analytics. We show how such complex microfluidic devices can be extended to the third dimension to facilitate liquid routing and how pairs of electrodes can be integrated into the channel walls yielding perfect electrostatics. Examples from droplet-based microfluidics show two to three orders of magnitude reduction in supply voltage over state-of-the-art at ultrahigh throughput rates for real-time droplet sorting and use of emulsion techniques to create functional vesicles to study biochemical reaction pathways. Another use case of a programmable synthesis system is chemical computing where complex chemical reaction networks are deployed to tackle non-linear classification tasks using a reservoir-computing approach.