Over the past two decades, there has been an increasing trend towards miniaturization of both biological and chemical sensors and their integration with miniaturized sample pre-processing and analysis systems. These miniaturized lab-on-chip devices have several functional advantages including low cost, their ability to analyze smaller samples, faster analysis time, suitability for automation, and increased reliability and repeatability. Electrical based sensing methods that transduce biological or chemical signals into the electrical domain are a dominant part of the lab-on-chip devices. A vital part of any electrochemical sensing system is the reference electrode, which is a probe that is capable of measuring the potential on the solution side of an electrochemical interface. Research on miniaturization of this crucial component and analysis of the parameters that affect its performance, stability and lifetime, is sparse. In this paper, we present the basic electrochemistry and thermodynamics of these reference electrodes and illustrate the uses of reference electrodes in electrochemical and biological measurements. Different electrochemical systems that are used as reference electrodes will be presented, and an overview of some contemporary advances in electrode miniaturization and their performance will be provided.

Monolithic plugs of poly(N-isopropylacrylamide) cross-linked with 5% methylenebisacrylamide have been prepared by photoinitiated polymerization within the channel of a microfluidic device. The volume change associated with the polymer phase transition at its lower critical solution temperature of 32 degrees C allows both the rapid swelling and the deswelling of the monoliths enabling the polymer to close or open the channel as it functions as a nonmechanical valve. Thermoelectric elements capable of changing the temperature of the system between 17 and 57 degrees C were used to actuate the valve. Flow through the device was monitored by fluorescence measurements via the laser-triggered photobleaching of a dye contained in the liquid phase. Photobleaching occurs quickly once the flow is stopped, and the time required to open and close the valve was 3.5 and 5.0 s, respectively. No changes in function were observed even after 120 open-close cycles. Although the 2-mm-long valve was prepared from a polymerization mixture consisting of only a 5% aqueous solution of monomers, it resists pressures of up to 1.38 MPa (200 psi) without observable structural damage.

The nematode (worm) Caenorhabditis elegans is one of the most widely studied organisms for biomedical research. Currently, C. elegans assays are performed either on petri dishes, 96-well plates or using pneumatically controlled microfluidic devices. In this work, we demonstrate that the electric field can be used as a powerful stimulus to control movement of worms in a microfluidic environment. We found that this response (termed electrotaxis) is directional, fully penetrant and highly sensitive. The characterization of electrotaxis revealed that it is mediated by neuronal activity that varies with the age and size of animals. Although the speed of swimming is unaffected by changes in the electric field strength and direction, our results show that each developmental stage responds to a specific range of electric field with a specific speed. Finally, we provide evidence that the exposure to the electric field has no discernible effect on the ability of animals to survive and reproduce. Our method has potential in precisely controlling, directing, and transporting worms in an efficient and automated manner. This opens up significant possibilities for high-throughput screening of C. elegans for drug discovery and other applications.

The lysis of cells in order to extract the nucleic acids or proteins inside it is a crucial unit operation in biomolecular analysis. This paper presents a critical evaluation of the various methods that are available both in the macro and micro scale for cell lysis. Various types of cells, the structure of their membranes are discussed initially. Then, various methods that are currently used to lyse cells in the macroscale are discussed and compared. Subsequently, popular methods for micro scale cell lysis and different microfluidic devices used are detailed with their advantages and disadvantages. Finally, a comparison of different techniques used in microfluidics platform has been presented which will be helpful to select method for a particular application.

Since their debut in 2012, triboelectric nanogenerators (TENGs) have attained high performance in terms of both energy density and instantaneous conversion, reaching up to 500 W m −2 and 85%, respectively, synchronous with multiple energy sources and hybridized designs. Here, a comprehensive review of the design guidelines of TENGs, their performance, and their designs in the context of Internet of Things (IoT) applications is presented. The development stages of TENGs in large-scale self-powered systems and technological applications enabled by harvesting energy from water waves or wind energy sources are also reviewed. This self-powered capability is essential considering that IoT applications should be capable of operation anywhere and anytime, supported by a network of energy harvesting systems in arbitrary environments. In addition, this review paper investigates the development of self-charging power units (SCPUs), which can be realized by pairing TENGs with energy storage devices, such as batteries and capacitors. Consequently, different designs of power management circuits, supercapacitors, and batteries that can be integrated with TENG devices are also reviewed. Finally, the significant factors that need to be addressed when designing and optimizing TENG-based systems for energy harvesting and self-powered sensing applications are discussed. Integrated Self-Powered Systems

This paper reports the development of microfluidic oxygenator (MFO) units designed for a lung assist device (LAD) for newborn infants. This device will be connected to the umbilical vessels like the natural placenta and provide gas exchange. The extracorporeal blood flow is only driven by the pressure difference between the umbilical artery and vein without the use of external pumps. The LAD is designed for use in ambient air (~21% of 760 mmHg). The main focus of this paper is the presentation of the development of the MFO units testing various membrane materials with human blood to enhance gas exchange and in the design of fluidic inlets to lower the pressure drop across the oxygenator. Four different membranes, including thin film PDMS, porous PDMS, and two different pore size porous polycarbonate membranes are compared in this study. Among them, the microfluidic oxygenator with porous PDMS membrane has the highest gas exchange rate of 1.46 μL min(-1) cm(2) for oxygen and 5.27 μL min(-1) cm(2) for carbon dioxide and performs better than a commercial hollow fiber-based oxygenator by 367 and 233%, respectively. A new tapered inlet configuration was designed to reduce the pressure drop across the oxygenator and showed a further 57% improvement over the traditional perpendicular inlet configuration.

A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 μL/min/cm(2) (0.3-0.5 mL/kg/min) and 6.4-10.1 μL/min/cm(2) (0.8-1.3 mL/kg/min) for O2 and CO2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 μg/cm(2) ). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65-2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (Fi O2  = 0.15) and was found to be 3.0 μL/min/cm(2) . These results are encouraging and support the feasibility of an artificial placental design for an LAD.

The nematode (worm) C. elegans is one of the widely studied animal model organisms in biology. It develops through 4 larval stages (L1-L4) in 2 to 3 days before becoming a young adult. Biological assays involving C. elegans frequently require a large number of animals that are appropriately staged and exhibit a similar behaviour. We have developed a new method to synchronize animals that relies on the electrotactic response (electric field-induced motion) of C. elegans to sort them in parallel based on their age, size and phenotype. By using local electric field traps in a microfluidic device, we can efficiently sort worms from a mixed culture in a semi-continuous flow manner (with a minimum throughput of 78 worms per minute per load-run) and obtain synchronized populations of animals. In addition to sorting larvae, our device can also distinguish between young and old adults efficiently. Unlike fluorescent based sorting systems that use active imaging based feedback, this method is passive and automatic and uses the innate behaviour of the worm. Considering that the entire procedure takes only a few minutes to run and is cost-effective, it promises to simplify and accelerate experiments requiring homogeneous cultures of worms as well as to facilitate isolation of mutants that have abnormal electrotaxis. More importantly, our method of isolating and separating worms using locomotion as a defining characteristic promises development of advanced microfluidics-based systems to study the neuronal basis of movement-related defects in worms and facilitate high-throughput chemical screening and drug discovery.