Multifarious Transit Gates for Programmable Delivery of Bio‐functionalized Matters

Programmable delivery of biological matter is indispensable for the massive arrays of individual objects in biochemical and biomedical applications. Although a digital manipulation of single cells has been implemented by the integrated circuits of micromagnetophoretic patterns with current wires, the complex fabrication process and multiple current operation steps restrict its practical application for biomolecule arrays. Here, a convenient approach using multifarious transit gates is proposed, for digital manipulation of biofunctionalized microrobotic particles that can pass through the local energy barriers by a time‐dependent pulsed magnetic field instead of multiple current wires. The multifarious transit gates including return, delay, and resistance linear gates, as well as dividing, reversed, and rectifying T‐junction gates, are investigated theoretically and experimentally for the programmable manipulation of microrobotic particles. The results demonstrate that, a suitable angle of the gating field at a suitable time zone is crucial to implement digital operations at integrated multifarious transit gates along bifurcation paths to trap microrobotic particles in specific apartments, paving the way for flexible on‐chip arrays of biomolecules and cells.     

Stochastic Particle Barcoding for Single‐Cell Tracking and Multiparametric Analysis

This study presents stochastic particle barcoding (SPB), a method for tracking cell identity across bioanalytical platforms. In this approach, single cells or small collections of cells are co‐encapsulated within an enzymatically‐degradable hydrogel block along with a random collection of fluorescent beads, whose number, color, and position encode the identity of the cell, enabling samples to be transferred in bulk between single‐cell assay platforms without losing the identity of individual cells. The application of SPB is demonstrated for transferring cells from a subnanoliter protein secretion/phenotyping array platform into a microtiter plate, with re‐identification accuracies in the plate assay of 96±2%. Encapsulated cells are recovered by digesting the hydrogel, allowing subsequent genotyping and phenotyping of cell lysates. Finally, a model scaling is developed to illustrate how different parameters affect the accuracy of SPB and to motivate scaling of the method to thousands of unique blocks.     

Microfluidic‐Based Approaches in Targeted Cell/Particle Separation Based on Physical Properties: Fundamentals and Applications

Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high‐efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label‐free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor‐intensive steps of labeling molecular signatures of cells. In general, microfluidic‐based cell sorting approaches can separate cells using “intrinsic” (e.g., fluid dynamic forces) versus “extrinsic” external forces (e.g., magnetic, electric field, etc.) and by using different properties of cells including size, density, deformability, shape, as well as electrical, magnetic, and compressibility/acoustic properties to select target cells from a heterogeneous cell population. In this work, principles and applications of the most commonly used label‐free microfluidic‐based cell separation methods are described. In particular, applications of microfluidic methods for the separation of circulating tumor cells, blood cells, immune cells, stem cells, and other biological cells are summarized. Computational approaches complementing such microfluidic methods are also explained. Finally, challenges and perspectives to further develop microfluidic‐based cell separation methods are discussed.     

Temperature Gradients Drive Bulk Flow Within Microchannel Lined by Fluid–Fluid Interfaces

Surface tension gradients induce Marangoni flow, which may be exploited for fluid transport. At the micrometer scale, these surface‐driven flows can be quite significant. By introducing fluid–fluid interfaces along the walls of microfluidic channels, bulk fluid flows driven by temperature gradients are observed. The temperature dependence of the fluid–fluid interfacial tension appears responsible for these flows. In this report, the design concept for a biocompatible microchannel capable of being powered by solar irradiation is provided. Using microscale particle image velocimetry, a bulk flow generated by apparent surface tension gradients along the walls is observed. The direction of flow relative to the imposed temperature gradient agrees with the expected surface tension gradient. The phenomenon's ability to replace bulky peripherals, like traditional syringe pumps, on a diagnostic microfluidic device that captures and detects leukocyte subpopulations within blood is demonstrated. Such microfluidic devices may be implemented for clinical assays at the point of care without the use of electricity.     

Microfluidic chips for point-of-care immunodiagnostics

We might be at the turning point where research in microfluidics undertaken in academia and industrial research laboratories, and substantially sponsored by public grants, may provide a range of portable and networked diagnostic devices. In this Progress Report, an overview on microfluidic devices that may become the next generation of point-of-care (POC) diagnostics is provided. First, we describe gaps and opportunities in medical diagnostics and how microfluidics can address these gaps using the example of immunodiagnostics. Next, we conceptualize how different technologies are converging into working microfluidic POC diagnostics devices. Technologies are explained from the perspective of sample interaction with components of a device. Specifically, we detail materials, surface treatment, sample processing, microfluidic elements (such as valves, pumps, and mixers), receptors, and analytes in the light of various biosensing concepts. Finally, we discuss the integration of components into accurate and reliable devices.     

Microfluidic Surface‐Enhanced Raman Scattering Sensors Based on Nanopillar Forests Realized by an Oxygen‐Plasma‐Stripping‐of‐Photoresist Technique

A novel surface‐enhanced Raman scattering (SERS) sensor is developed for real‐time and highly repeatable detection of trace chemical and biological indicators. The sensor consists of a polydimethylsiloxane (PDMS) microchannel cap and a nanopillar forest‐based open SERS‐active substrate. The nanopillar forests are fabricated based on a new oxygen‐plasma‐stripping‐of‐photoresist technique. The enhancement factor (EF) of the SERS‐active substrate reaches 6.06 × 10⁶, and the EF of the SERS sensor is about 4 times lower due to the influence of the PDMS cap. However, the sensor shows much higher measurement repeatability than the open substrate, and it reduces the sample preparation time from several hours to a few minutes, which makes the device more reliable and facile for trace chemical and biological analysis.     

Art‐on‐a‐Chip: Preserving Microfluidic Chips for Visualization and Permanent Display

“After a certain high level of technical skill is achieved, science and art tend to coalesce in aesthetics, plasticity, and form. The greatest scientists are always artists as well.” said Albert Einstein. Currently, photographic images bridge the gap between microfluidic/lab‐on‐a‐chip devices and art. However, the microfluidic chip itself should be a form of art. Here, novel vibrant epoxy dyes are presented in combination with a simple process to fill and preserve microfluidic chips, to produce microfluidic art or art‐on‐a‐chip. In addition, this process can be used to produce epoxy dye patterned substrates that preserve the geometry of the microfluidic channels—height within 10% of the mold master. This simple approach for preserving microfluidic chips with vibrant, colorful, and long‐lasting epoxy dyes creates microfluidic chips that can easily be visualized and photographed repeatedly, for at least 11 years, and hence enabling researchers to showcase their microfluidic chips to potential graduate students, investors, and collaborators.