Abstract
Neuroscience
An Organic Electronic Biomimetic Neuron Enables Auto-Regulated Neuromodulation
Simon et al. introduce a new therapeutic method for neurological disorders. An organic electronic biomimetic neuron precisely addresses malfunctioning signaling pathways using endogenous substances. The authors realize the fundamental function of neurons—chemical-to-electrical-to-chemical signal transduction—by connecting enzyme-based amperometric biosensors and organic electronic ion pumps. The biosensors sense chemical signals and subsequently electrophoretically deliver chemical substances as a response.
The biosensor developed by the authors has a dynamic range of 5 to 80 µM, which is physiologically relevant, with a linear response greater than 20 µm with approximately 0.1 nA/µM slope. When threshold concentrations are sensed, the biosensor activates a local or distant neurotransmitter using organic electronic ion pumps. For example, changes of 20 µM glutamate or acetylcholine trigger diffusive delivery of acetylcholine, resulting in activated cells via receptor-mediated signaling that are observed in real time via single-cell ratiometric Ca2+ imaging.
With these results, the authors demonstrate the potential of the organic electronic biomimetic neuron to mimic the function of projection neurons capable of long-range neuronal signaling. With this device, the authors also demonstrate conversion of glutamate-induced descending neuromuscular signals into acetylcholine-mediated muscular activation signals, which provide hope for bridging injured sites and active prosthetics. (Simon, D. T., et al. Bios. Bioelec.
Neural Probes with Multidrug Delivery Capability
Multifunctional neural probes are very useful tools for studying the brain as they can record neural signals and modulate the signals with various stimuli. Shin et al. present a neural probe with an embedded microfluidic channel (chemtrode) capable of multidrug delivery. A three-inlet microfluidic chip with staggered herringbone mixer is integrated in the chemtrode. This chip serves as an interface for the chemtrode and allows for efficient delivery of small volumes of multiple or concentration-modulated drugs via chaotic mixing.
With this chip, combinatorial inputs of three chemicals can be infused with a flow rate of (170 nL/min), with a small swept volume of only 66 nL. The authors demonstrate the potential of the chemtrode as in vivo mice experiments. Various substances, including a chemical (pilocarpine or tetrodotoxin at inlet 1), a buffer solution (saline at inlet 2), and 4′,6-diamidino-2-phenylindole (DAPI at inlet 3) are simultaneously infused locally into a mouse brain. Neural activities are modulated by varying the concentration of the chemical, and the cells at the target region (CA1 in hippocampus) are locally stained.
With this chip, multiple sets of data can be recorded using only one mouse through a single implantation of the chemtrode. The authors summarize the advantages of the devices as (1) multidrug delivery through a compact packaging with a small swept volume and (2) simultaneous recording to monitor near real-time effects on neural signals, which results in more effective experiments and less scarified animals. (Shin, H., et al. Lab Chip
Real-Time Monitoring of Discrete Synaptic Release Events and Excitatory Potentials within Self-Reconstructed Neuromuscular Junctions
Understanding chemical synaptic transmission is key to studying brain functions, and to date, real-time monitoring of chemical synaptic transmission during neuronal communication remains a great challenge. Li et al. introduce a microfluidic device to help address this issue.
This device allows for assembly of in vivo–like oriented neural networks between superior cervical ganglion (SCG) neurons and their effector smooth muscle cells (SMC), and is also capable of amperometric detection of individual neurotransmitter release events inside a functional SCG-SMC synapse using carbon fiber nanoelectrodes and recording postsynaptic potential using glass nanopipette electrodes. With this device, the authors claim, for the first time, monitoring of in situ chemical synaptic transmission under close to in vivo conditions, which could lead to new findings in the nature of neuronal communications. (Li, Y. T., et al. Angew. Chem.
High-Throughput Droplet Control
Kilo-Scale Droplet Generation in Three-Dimensional Monolithic Elastomer Device (3D MED)
Droplet-based microfluidics is an extremely powerful tool for multiple applications, including materials synthesis and high-throughput biological assays. Recently, there has been a great deal of interest in transitioning droplet microfluidics technology into commercial applications. One of the challenges is the scale-up of droplet generation from the laboratory (<10 mL/h) to the industrial (>1 L/h) scale.
Jeong et al. share a three-dimensional monolithic elastomer device (3D MED) that targets mass production of monodisperse emulsion droplets. The authors use a double-sided imprinting technique to create massive 3D microchannel networks in a single elastomer piece that includes 1000 parallel-flow focusing generators. Unlike previous efforts in parallelizes droplet generation, the 3D MED does not require alignment and bonding of multiple pieces, thus making it easy and cost-effective to reach kilo-scale generation of droplets.
Using this approach, the authors demonstrate mass production of water-in-oil (W/O) emulsion droplets at production rates as high as 1.5 L/h with a coefficient of variation of droplet diameter of only 6.6%. With its simplicity, robustness, and manufacturability, the authors believe their 3D MED architecture is well suited to bridge the gap between laboratory settings and industry to enable commercialization of droplet-based microfluidic technologies. (Jeong, H. H., et al. Lab Chip
Efficient Cell Pairing in Droplets Using Dual-Color Sorting
Microfluidic droplet is a powerful tool for screening and manipulation of cells. Cells can be encapsulated into droplets that can be transported, analyzed, and sorted using a library of microfluidic droplet tools. In many cases, however, assays are limited to single-cell types, and multi-cell–type analysis is needed in many scenarios such as interaction of different cells. For example, screening of antibody-secreting cells requires an additional reporter cell present in the same droplet.
Traditionally, the probability of a generation of droplets hosting exactly one cell of two different types is low. To address this challenge, Hu et al. present a method involving staining different cell types with different fluorescent dyes. After encapsulating cells into droplets, the emulsion is injected into a dual-color sorting device capable of high magnification and fixation of the cells close to the focal plane, which results in collection of droplets with exactly two different cells. With this approach, the authors demonstrate an efficiency of up to 86.7% and believe this work is paving the way for a variety of cell-based assays in droplets. (Hu, H., et al. Lab Chip
Manipulating Oil Droplets by Superamphiphobic Nozzle
Wu et al. report a novel method for oil droplet generation using a superamphiphobic nozzle. The key to this nozzle is its super-antiwetting property, which allows it to manipulate tiny oil droplets of varied volumes with high accuracy and reduced liquid tension. Using this nozzle, the authors achieve printing of various inks with low surface tension at picoliter scale for high-resolution 3D structures. The authors believe this method can provide significant advantages for future liquid transportation and ink-jet printing devices. (Wu, L., et al. Small
Wearable Technologies
Robust and Soft Elastomeric Electronics Tolerant to Our Daily Lives
For wearable electronic devices to be fully integrated into clothes, the devices themselves must be as robust and soft as the clothes themselves. To date, no wearable electronic device has been able to achieve this because all previously developed wearable devices contain components fabricated from brittle materials such as metals.
Sekiguchi et al. report achieving a robust and soft elastomeric device by using single-walled carbon nanotubes that provide necessary electronic functionalities while maintaining elastometric characteristics that match clothes. The authors demonstrate that their elastomeric field affects transistors based on carbon nanotubes that can tolerate punishments similar to what clothes experience, such as stretch, bend, compression, impact, and laundry. This design approach provides possibilities for electronics in wide range of wearable applications. (Sekiguchi, A., et al. Nano Lett.
Stretchable Heater Using Ligand-Exchanged Silver Nanowire Nanocomposite for Wearable Articular Thermotherapy
Thermal therapy is one of the most popular physiotherapies and is particularly useful for treating joint injuries. Traditionally, the devices for thermal therapy consist of heat packs and wraps that can be rigid and heavy and thus uncomfortable to wear.
Choi et al. have developed a soft, thin, and stretchable heater with a nanocomposite of silver nanowires and a thermoplastic elastomer. The authors use a ligand exchange reaction to form a highly conductive and homogeneous nanocomposite. The nanocomposite is patterned in serpentine-mesh structures on the elastomer, which is subsequently conformably laminated on curvilinear joints, resulting in effective heat transfer even during motion. By combining a homogeneous conductive elastomer, stretchable design, and a custom-designed electronic band, the authors have created a much improved wearable system for long-term, continuous articular thermotherapy. (Choi, S., et al. ACS Nano.
Ultratrace Measurement of Acetone from Skin Using Zeolite: Toward Development of a Wearable Monitor of Fat Metabolism
Analysis of gases sampled from skin and breath is receiving much attention as a way to develop noninvasive point-of-care diagnostic methods. Acetone emitted from skin is recognized as a potential marker for a fat metabolism disorder that is associated with diet and exercise. Analyzing skin acetone is challenging, however, because of its low concentration.
Yamada et al. present a study using zeolite to concentrate skin acetone for subsequent semiconductor-based analysis. The authors compare the adsorption and desorption characteristics of several zeolites with different structures and hydrophobicities and show a particular hydrophobic zeolite with pores that are slightly larger than the acetone molecule diameter, offering the best adsorption efficiency. Acetone from simulated skin is concentrated by zeolite and subsequently detected by a semiconductor-based gas sensor. The authors believe their results are paving the way for a wearable analyzer for skin acetone to prevent and manage lifestyle-related diseases. (Yamada Y., et al. Anal. Chem.
Transparent Stretchable Self-Powered Patchable Sensor Platform with Ultrasensitive Recognition of Human Activities
Hwang et al. report a novel method for tracking human activities. It involves using a self-powered patchable strain sensor to recognize strains on human skin as a result of subtle movements of muscles in the internal organs, such as the esophagus and trachea, and the movement of joints. The sensor is constructed using multifunctional nanocomposites of low-density silver nanowires with a conductive elastomer of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate/polyurethane, which offers high sensitivity, stretchability, and optical transparency. The same nanocomposite also forms a supercapacitor and triboelectric nanogenerator, which when combined with the ultra-low-power consumption of the sensor, renders the whole monitoring system self-sufficient in terms of power. This new method offers possibilities for developing autonomous invisible skin strain sensors for a wide variety of applications. (Hwang, B.-U., et al. ACS Nano.
Mobile Diagnostics
Smartphone-Based Point-of-Care Testing of Salivary α-amylase for Personal Psychological Measurement
Zhang et al. report a smartphone-based potentiometric biosensor for point-of-care detection of salivary α-amylase (sAA), which is an important biomarker for autonomic nervous system activity and has important implication in point-of-care mental health monitoring. A potentiometric reader and a sensor chip with preloaded reagents are coupled with a smartphone with a USB port. The saliva sample is drawn into the reaction zone on the sensor chip, and the reaction with the preloaded reagents results in conversion of an electron mediator Fe(CN)63− to Fe(CN)64−, resulting in a potential shift that can be measured by the phone. Using this system, the sAA is measured in real human saliva samples, and quantitative analysis can be achieved within 5 min. The authors show strong agreement between the mobile system and the reference method that can be achieved, and the results also correlate well with psychological states of the test subjects. (Zhang, L., et al. Analyst
Integrated Quantum Dot Barcode Smartphone Optical Device for Wireless Multiplexed Diagnosis of Infected Patients
Inorganic nanoparticles have great potential for creating engineering barcodes for rapidly detecting diseases. The development and full clinical potential of these barcodes, however, are hindered by their lack of sensitivity and their need for a complex read-out system. Ming et al. report a new mobile system created by combining quantum dot barcodes with smartphones and isothermal amplification.
The resulting system is capable of detecting as few as 1000 viral genetic copies per milliliter and has potential applications in diagnosis of infectious diseases such as HIV and hepatitis B. More importantly, the barcode technology makes it possible for simultaneous detection of multiple infectious agents. The authors believe this new integrated system can be useful in surveillance of infectious diseases and has the potential to accelerate knowledge exchange transfer of emerging or exigent disease threats on a global scale. (Ming, K., et al. ACS Nano.
Portable Smartphone Quantitation of Prostate-Specific Antigen (PSA) in a Fluoropolymer Microfluidic Device
Barbosa et al. introduce a new, power-free and flexible detection system named MCFphone for portable colorimetric and fluorescence quantitative sandwich immunoassay detection of prostate-specific antigens (PSA). The MCFphone includes a smartphone, a magnifying lens, a simple light source, and a miniaturized immunoassay platform, the Microcapillary Film (MCF).
Thanks to the excellent transparency and flat geometry of fluoropolymer MCF, a dynamic range 0.9 to 60 ng/mL with <7% precision in 13 min can be achieved for PSA detection using enzymatic amplification and a chromogenic substrate. It is possible to achieve an even lower detection limit from 0.4 to 0.08 ng/mL in whole-blood samples if a fluorescence substrate is used. With its ability to perform rapid colorimetric quantitative and highly sensitive fluorescence tests with good percentage recovery, the authors claim the MCFphone represents a major step in the integration of a new generation of inexpensive and portable microfluidic devices with commercial immunoassay reagents and off-the-shelf smartphone technology. (Barbosa, A. I., et al. Bios. Bioelec.
Smartphone Dongle for Simultaneous Measurement of Hemoglobin Concentration and Detection of HIV Antibodies
Guo et al. demonstrate a microfluidic-based smartphone dongle that simultaneously measures hemoglobin concentration and detects HIV antibodies. This is a challenge because these two arrays traditionally belong to two different classes of tests. By tweaking an immunoassay based on optical density of silver precipitation on gold colloids, which was previously developed for HIV antibody measurement, the authors manage to measure hemoglobin using the same colorimetric working principle—by lysing the whole-blood components with CHAPS detergent—and a highly reproducible hemoglobin concentration is achieved.
The authors test the dual-test device on real patient samples and compare the results with those obtained using a commercial analyzer, and they show that hemoglobin concentrations reported by the device are accurate within 1.2 g/dL and HIV immunoassays show 95% sensitivity and 95% specificity. This work is a great example demonstrating that two classes of diagnostic tests (a colorimetric-based quantitative measurement and an immunoassay based on silver precipitation on gold colloids) can be combined into a low-cost, fast, and low-power dongle that works with smartphones to enable better clinical utility of mobile diagnostic devices. (Guo, T., et al. Lab Chip
Paper-Based Analytical Devices
Paper-Based RNA Extraction, In Situ Isothermal Amplification, and Lateral Flow Detection for Low-Cost, Rapid Diagnosis of Influenza A (H1N1) from Clinical Specimens
Rodriguez et al. share a paper-based analytical device that targets H1N1 detection and has disproportionately affected the developing world. The key to addressing the challenge is the difficulty of implementing highly sensitive and fast turnaround diagnostic assays and instruments in a resource-limited environment.
By leveraging recent developments in paper microfluidics, the authors demonstrate a paper-based assay that allows for the extraction and purification of RNA directly from human clinical nasopharyngeal specimens through a poly(ether sulfone) paper matrix, H1N1-specific in situ isothermal amplification directly within the same paper matrix, and immediate visual detection on lateral flow strips. With such an approach, the authors achieve the complete sample-to-answer assay in a resource-limiting setting in just 45 min. This low-cost rapid diagnostic method also has a clinically relevant viral load detection limit of 106 copies/mL, 10-fold lower than current rapid immunoassays. (Rodriguez, N., et al. Anal. Chem.
Cell Chemotaxis on Paper for Diagnostics
Microfluidic chemotaxis platforms have been widely used in applications in cell migration studies and diagnostics. Traditional microfluidic chemotaxis systems are based on free-flow liquid systems that are based on channels and pumps that are difficult to set up and take a long time to establish. To address this challenge, Walsh et al. have developed a low-cost paper fluidic device that is capable of delivering a quasi-stable (at least 20 min) and rapidly generated (<1 s) chemokine gradient system.
With this device, the authors create an easy-to-assemble system for studying cell migration response over short timeframes. In a proof-of-concept experiment, human pan-T cells are observed to show significant directed migration to the chemokine gradient. The authors believe this new technique has great potential to be further developed into chemotactic platforms for point-of-care diagnostics. (Walsh, D. I., et al. Anal. Chem.