Sub-Millisecond Integrated Mix-and-Inject Microfluidic Sample Delivery Devices

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.

Predicting the fluid behavior of random microfluidic mixers using convolutional neural networks

Predicting the fluid behavior of complex microfluidic channel networks using convolutional neural networks.

Mix-and-diffuse serial synchrotron crystallography

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.

Fabrication of Tunable Silk Materials Through Microfluidic Mixers

A common method to precisely control the material properties is to evenly distribute functional nanomaterials within the substrate. For example, it is possible to mix a silk solution and nanomaterials together to form one tuned silk sample. However, the nanomaterials are likely to aggregate in the traditional manual mixing processes. Here we report a pilot study of utilizing specific microfluidic mixing designs to achieve a uniform nanomaterial distribution with minimal aggregation. Mixing patterns are created based on classic designs and then validated by experimental results. The devices are fabricated on polydimethylsiloxane (PDMS) using 3D printed molds and soft lithography for rapid replication. The initial mixing performance is validated through the mixing of two solutions with colored dyes. The microfluidic mixer designs are further analyzed by creating silk-based film samples. The cured film is inspected with scanning electron microscopy (SEM) to reveal the distribution uniformity of the dye particles within the silk material matrix. Our preliminary results show that the microfluidic mixing produces uniform distribution of dye particles. Because the microfluidic device can be used as a continuous mixing tool, we believe it will provide a powerful platform for better preparation of silk materials. By using different types of nanomaterials such as graphite (demonstrated in this study), graphene, carbon nanotubes, and magnetic nanoparticles, the resulting silk samples can be fine-tuned with desired electrical, mechanical, and magnetic properties.