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Poly(dimethylsiloxane) (PDMS) is likely the most popular material for microfluidic devices in lab-on-a-chip and other biomedical applications. However, the hydrophobicity of PDMS leads to non-specific adsorption of proteins and other molecules such as therapeutic drugs, limiting its broader use. Here, we introduce a simple method for preparing PDMS materials to improve hydrophilicity and decrease non-specific protein adsorption while retaining cellular biocompatibility, transparency, and good mechanical properties without the need for any post-cure surface treatment. This approach utilizes smart copolymers comprised of poly(ethylene glycol) (PEG) and PDMS segments (PDMS-PEG) that, when blended with PDMS during device manufacture, spontaneously segregate to surfaces in contact with aqueous solutions and reduce the hydrophobicity without any added manufacturing steps. PDMS-PEG-modified PDMS samples showed contact angles as low as 23.6° ± 1° and retained this hydrophilicity for at least twenty months. Their improved wettability was confirmed using capillary flow experiments. Modified devices exhibited considerably reduced non-specific adsorption of albumin, lysozyme, and immunoglobulin G. The modified PDMS was biocompatible, displaying no adverse effects when used in a simple liver-on-a-chip model using primary rat hepatocytes. This PDMS modification method can be further applied in analytical separations, biosensing, cell studies, and drug-related studies.

There is a great need for techniques which enable reproducible separation of extracellular vesicles (EVs) from biofluids with high recovery, purity and throughput. The development of new techniques for isolation of EVs from minute sample volumes is instrumental in enabling EV-based biomarker profiling in large biobank cohorts and paves the way to improved diagnostic profiles in precision medicine. Recent advances in microfluidics-based devices offer a toolbox for separating EVs from small sample volumes. Microfluidic devices that have been used in EV isolation utilise different fundamental principles and rely largely on benefits of scaling laws as the biofluid processing is miniaturised to chip level. Here, we review the progress in the practicality and performance of both passive devices (such as mechanical filtering and hydrodynamic focusing) and active devices (using magnetic, electric or acoustic fields). As it stands, many microfluidic devices isolate intact EV populations at higher purities than centrifugation, precipitation or size-exclusion chromatography. However, this comes at a cost. We address challenges (in particular low throughput, clogging risks and ability to process biofluids) and highlight the need for more improvements in microfluidic devices. Finally, we conclude that there is a need to refine and standardise these lab-on-a-chip techniques to meet the growing interest in the diagnostic and therapeutic value of purified EVs. Graphical abstract

Periodontitis has become one of the most universal chronic inflammatory diseases worldwide. Subclinical symptom progression, ultimately leading to permanent damage, calls for early diagnosis and long-term monitoring. However, traditional clinical diagnostic methods are complex and expensive, and cannot meet these requirements. Recently, with more biomarkers and the development of new technologies, various point-of-care testing (POCT) platforms have been developed for periodontitis diagnosis and monitoring. These are easy to perform, rapid, low-cost, and are perfectly suited for high-frequency diagnosis of periodontitis at the point-of-care (POC). We summarize existing biomarkers of different periodontitis stages and recent developed POCT platforms (including lab-on-a-chip, paper-based platforms, and chairside tests), discuss their existing challenges and future potential, and provide some inspiration and guidelines for future POC periodontitis testing. Periodontitis has wide prevalence and distribution, and is associated with the progression of several systemic diseases (e.g., diabetes, atherosclerosis, cancers, and Alzheimer's disease). Preventing and treating periodontitis is beneficial to oral and general health, and diagnosis and surveillance of periodontitis are especially important. Existing clinical diagnostic methods for periodontitis can reflect its severity and previous periodontal destruction, but they fail to reflect its present state or allow monitoring and predict its progress. By contrast, periodontitis-related biomarkers can indicate current disease conditions and evaluate treatment effects and future risk. POCT can detect periodontitis biomarkers onsite within 20minutes. Its low cost, ease of use, and speed can help people to pay closer attention to their oral health and decrease the need for dental procedures.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level complementary metal-oxide semiconductor (CMOS) chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

Chain reactions, characterized by initiation, propagation and termination, are stochastic at microscopic scales and underlie vital chemical (for example, combustion engines), nuclear and biotechnological (for example, polymerase chain reaction) applications 1 , 2 , 3 , 4 – 5 . At macroscopic scales, chain reactions are deterministic and limited to applications for entertainment and art such as falling dominoes and Rube Goldberg machines. On the other hand, the microfluidic lab-on-a-chip (also called a micro-total analysis system) 6 , 7 was visualized as an integrated chip, akin to microelectronic integrated circuits, yet in practice remains dependent on cumbersome peripherals, connections and a computer for automation 8 , 9 , 10 – 11 . Capillary microfluidics integrate energy supply and flow control onto a single chip by using capillary phenomena, but programmability remains rudimentary with at most a handful (eight) operations possible 12 , 13 , 14 , 15 , 16 , 17 , 18 – 19 . Here we introduce the microfluidic chain reaction (MCR) as the conditional, structurally programmed propagation of capillary flow events. Monolithic chips integrating a MCR are three-dimensionally printed, and powered by the free energy of a paper pump, autonomously execute liquid handling algorithms step-by-step. With MCR, we automated (1) the sequential release of 300 aliquots across chained, interconnected chips, (2) a protocol for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies detection in saliva and (3) a thrombin generation assay by continuous subsampling and analysis of coagulation-activated plasma with parallel operations including timers, iterative cycles of synchronous flow and stop-flow operations. MCRs are untethered from and unencumbered by peripherals, encode programs structurally in situ and can form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics. Microfluidic chain reactions encode programs structurally in situ, and can form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture.

Liquid manipulation is the foundation of most laboratory processes. For macroscale liquid handling, both do-it-yourself and commercial robotic systems are available; however, for microscale, reagents are expensive and sample preparation is difficult. Over the last decade, lab-on-a-chip (LOC) systems have come to serve for microscale liquid manipulation; however, lacking automation and multi-functionality. Despite their potential synergies, each has grown separately and no suitable interface yet exists to link macro-level robotics with micro-level LOC or microfluidic devices. Here, we present a robot-assisted acoustofluidic end effector (RAEE) system, comprising a robotic arm and an acoustofluidic end effector, that combines robotics and microfluidic functionalities. We further carried out fluid pumping, particle and zebrafish embryo trapping, and mobile mixing of complex viscous liquids. Finally, we pre-programmed the RAEE to perform automated mixing of viscous liquids in well plates, illustrating its versatility for the automatic execution of chemical processes. Lab-on-a-chip systems have been widely used in microscale liquid manipulation and greatly benefit from automation. Durrer et al. show a robot-assisted acoustofluidic end effector system, comprising a robotic arm and an acoustofluidic device, that combines both robotic and microfluidic functionalities.

Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro . The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.

Multiplexed point-of-care testing (xPOCT), which is simultaneous on-site detection of different analytes from a single specimen, has recently gained increasing importance for clinical diagnostics, with emerging applications in resource-limited settings (such as in the developing world, in doctors’ offices, or directly at home). Nevertheless, only single-analyte approaches are typically considered as the major paradigm in many reviews of point-of-care testing. Here, we comprehensively review the present diagnostic systems and techniques for xPOCT applications. Different multiplexing technologies (e.g., bead- or array-based systems) are considered along with their detection methods (e.g., electrochemical or optical). We also address the unmet needs and challenges of xPOCT. Finally, we critically summarize the in-field applicability and the future perspectives of the presented approaches. Simultaneous on-site measurement of different substances from a single sample, called multiplexed point-of-care testing, has recently become more and more important for in vitro diagnostics. The major aim for the development of xPOCT systems is the smart combination of a high-performing device with a low system complexity. Thus, the on-site tests are realized in a short time by non-experts and ensure comparable results with clinical and central laboratory findings. A multiplexing capability of up to 10 analytes has been sufficient for many recent xPOCT applications. The future of xPOCT devices will be driven by novel biotechnologies (e.g., aptamers) or targets (e.g., circulating RNAs or tumor cells, exosomes, and miRNAs), as well as applications like personalized medicine, homecare monitoring, and wearables.

Zika virus (ZIKV) infection, primarily transmitted by mosquitoes, causes various neurologic disorders. To differentiate ZIKV from other arboviruses, such as dengue, chikungunya, and yellow fever viruses, a highly specific, sensitive, and automated detection system is needed for point-of-care (POC) settings. To detect ZIKV at POC settings, we have developed a fully automated lab-on-a-chip microfluidic platform for rapid disease detection by using reverse transcription loop-mediated isothermal amplification. The developed setup consists of a microfluidic chip, a platform for magnetic actuation, and a heater along with the sensor to precisely control the temperature for the target amplification. The platform accurately controls the movement of the magnetic beads that enable the isolation and purification of the target nucleotides adhered to their surface for the amplification and disease detection on the microfluidic chip. Within 40 minutes, change in color due to the presence of ZIKV amplicons was visually observed with the spiked plasma samples in the end point analysis. Also, we have accurately and specifically identified ZIKV in a small number of de-identified clinical samples. All-inclusive, the developed fully automated POC ZIKV diagnostic chip is rapid, simple, easy to use, inexpensive, and suitable for the areas where facilities are limited.