Ultra-low-cost fabrication of polymer-based microfluidic devices with diode laser ablation Abstract In this work, a diode laser ablation approach was used for the fabrication of PMMA-based microfluidic devices. Compared with the conventional CO2 or femtosecond laser fabrication method, the proposed laser ablation method based on diode laser significantly lowered the cost in the fabrication of polymer-based microfluidic devices with comparable resolution and surface quality. PMMA substrate was used for the laser ablation process, due to the transparency of PMMA in the diode laser’s working wavelength, a layer of Kraft tape was applied on the surface of PMMA for the absorption of laser energy, and microchannels were then achieved on the surface of PMMA with the proposed low-cost diode laser system. The comparison between the proposed method and the CO2laser ablation method was also conducted in this study. The profile of the fabricated microchannels was carefully characterized, several microfluidic devices were also fabricated for the demonstration of the proposed fabrication method using a diode laser.

A review of microsampling techniques and their social impact Abstract Conventional skin and blood sampling techniques for disease diagnosis, though effective, are often highly invasive and some even suffer from variations in analysis. With the improvements in molecular detection, the amount of starting sample quantity needed has significantly reduced in some diagnostic procedures, and this has led to an increased interest in microsampling techniques for disease biomarker detection. The miniaturization of sampling platforms driven by microsampling has the potential to shift disease diagnosis and monitoring closer to the point of care. The faster turnaround time for actionable results has improved patient care. The variations in sample quantification and analysis remain a challenge in the microsampling field. The future of microsampling looks promising. Emerging techniques are being clinically tested and monitored by regulatory bodies. This process is leading to safer and more reliable diagnostic platforms. This review discusses the advantages and disadvantages of current skin and blood microsampling techniques.

Untethered microgripper-the dexterous hand at microscale Abstract Untethered microgrippers that can navigate in hard-to-reach and unpredictable environments are significantly important for biomedical applications such as targeted drug delivery, micromanipulation, minimally invasive surgery and in vivo biopsy. Compared with the traditional tethered microgrippers, the wireless microgrippers, due to the exceptional characteristics such as miniaturized size, untethered actuation, dexterous and autonomous motion, are projected to be promising microtools in various future applications. In this review, we categorize the untethered microgrippers into five major classes, i.e. microgrippers responsive to thermal, microgrippers actuated by magnetic fields, microgrippers responsive to chemicals, light-driven microgrippers and hybrid actuated microgrippers. Firstly, the actuation mechanisms of these microgrippers are introduced. The challenges faced by these microgrippers are also covered in this part. With that, the fabrication methods of these microgrippers are summarized. Subsequently, the applications of microgrippers are presented. Additionally, we conduct a comparison among different actuation mechanisms to explore the advantages and potential challenges of various types of microgrippers. In the end of this review, conclusions and outlook of the development and potential applications of the microgrippers are discussed.

Microfluidics-based device for the measurement of blood viscosity and its modeling based on shear rate, temperature, and heparin concentration Abstract Blood viscosity measurements are crucial for the diagnosis and understanding of a range of hematological and cardiovascular diseases. Such measurements are heavily used in monitoring patients during and after surgeries, which necessitates the development of a highly accurate viscometer that uses a minimal amount of blood. In this work, we have designed and implemented a microfluidic device that was used to measure fluid viscosity with a high accuracy using less than 10 μl of blood. The device was further used to construct a blood viscosity model based on temperature, shear rate, and anti-coagulant concentration. The model has an R-squared value of 0.950. Finally, blood protein content was changed to simulate diseased conditions and blood viscosity was measured using the device and estimated using the model constructed in this work. Simulated diseased conditions were clearly detected when comparing estimated viscosity values using the model and the measured values using the device, proving the applicability of the setup in the detection of rheological anomalies and in disease diagnosis.

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion Abstract Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG-b-PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG-b-PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG-b-PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.

Glioblastoma Multiforme heterogeneity profiling with solid-state micropores Abstract Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. It is characterized by widespread heterogeneity at the cellular and molecular levels. The detection of this heterogeneity is valuable for accurate diagnosis. Herein, solid-state 20 μm diameter micropore made in thin suspended silicon dioxide membrane is used as cell sensor device. The device relies on a cell’s mechano-physical properties as an indicator to differentiate between the subtypes of GBM. A library of GBM cell lines (U251, U87, D54 EGFRviii, and G55) was created by measuring the differences in cell’s micropore translocation properties from their distinct electrical profiles. Each GBM subtype has distinct phenotype and this was delineated in their cell translocation behaviors. The library was used to distinguish cells from samples of brain tumor patients. The micropore device accurately profiled GBM patient samples for cell subtypes by comparing data with the GBM library. The micropore approach is simple, can be implemented at low cost and can be used in the clinical setups and operation theaters to detect and identify GBM subtypes from patient samples.

Make it simple: long-term stable gradient generation in a microfluidic microdevice Abstract Microfluidics-based gradient generators have been used for various biological applications, specifically chemotaxis in cell culture. However, the ability to generate and maintain long term gradients alongside the ability to quickly switch solutions is a challenge of the current microfabricated systems. In this study, a simple flow-driven microfluidic system was developed to achieve long-term stable concentration gradients. Computational modelling was performed to highlight the fluid dynamics as well as to verify the ability of maintaining stable gradients over 7 days. Numerical simulation was analysed to evaluate the static pressure, velocity magnitude and wall shear stress distribution in the chamber. A microdevice fabricated with polydimethylsiloxane (PDMS), using a standard soft lithography technique is presented. It consists of eight parallel microchannels (5 μm × 30 μm × 1,800 μm) linking source and sink chambers; a syringe pump drives fluid through the sink chamber, advection/diffusion from source to sink establishes a gradient. A gradient of a fluorescent dye was generated under the low flow control at 1–10 μl/h of a simple syringe pump equipped with a pulsation damper that was comparable to a pulseless microfluidic pump. Concentration gradients were formed in 1 h and stable from 2 h out to 5 days and consuming less than 1.0 ml of solution. This study focuses on a novel solution to achieve a long-term microfluidic gradient generator using simple engineering techniques of biomedical microdevices.

Evaluation of biological synthesized platinum nanoparticles using Ononidis radix extract on the cell lung carcinoma A549 Abstract Due to the search for new methods for synthesizing nanomaterials, this work proposes the biological synthesis of platinum nanoparticles using Ononidis radix extract. The synthesized platinum nanoparticles were characterized by UV-Vis, Scanning Electron Microscopy (SEM) with EDS profile, Fourier transform infrared spectroscopy (FTIR), Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM). The examination conducted by means of Transmission Electron Microscopy showed the presence of spherical and hexagonal platinum nanoparticles. Atomic Force Microscopy indicated the presence of locally agglomerated nanoparticles whose size was about 4 nm. The study also examined the influence of platinum nanoparticles on human non-small cell lung carcinoma cells A549. It was found that the mortality of cells cultured together with platinum nanoparticles increased, and the proliferative activity of A549 cells decreased gradually over time in proportion to the increasing concentration of the test substance. Graphical abstract

Selective stimulation of bullfrog sciatic nerve by gold nanorod assisted combined electrical and near-infrared stimulation Abstract Selective stimulation of the nervous system is an important way to improve the therapeutic efficacy and minimize side effects. This paper introduces an improved method using combined electrical and near-infrared stimulation to realize selective excitation and inhibition of different sciatic nerve branches. Both the electrical stimulation and the near-infrared laser are added to the main trunk of the sciatic nerve, and gold nanorods are injected into the light irradiation point of the nerve to increase the absorption of light. Two cuff recording electrodes are added to the two sciatic nerve branches, respectively. The compound nerve action potential recorded by the cuff electrode is transmitted to the physiological signal instrument. In the experiment, selective activation and inhibition of the two nerve branches are achieved by adjusting the electrical stimulation parameters, the light stimulus parameters and the location of the light. These results demonstrate that combined electrical and near-infrared stimulation, which can effectively activate or suppress the different nerve fibers in the nerve fiber bundle, is suitable for selective regulation of peripheral nerve. Meanwhile, the photoelectric combined stimulation can reduce both the electrical energy and light energy needed for the stimulation, and reduce the electrical damage and light damage to the nerve.

Magnetic field assisted laser fabrication and electrical characterizations of metal dry Biolectrode with surface microstructures Abstract Magnetic field assisted laser fabrication is proposed to process metal dry bioelectrode with surface microstructures. The effects of magnetic flux density on the geometrical dimension of surface microstructures of bioelectrode is investigated. The electrode-skin contact impedance is then studied using the two-electrode measurement method. Finally, electromyography (EMG) signal is recorded using bioelectrodes processed in different magnetic flux density. Our results show that the magnetic field has obvious influences on the height and bottom width of microstructure of bioelectrode. When a magnetic field of 100 mT is selected, larger height-width ratio of microstructures is obtained, which provides a stronger ability to penetrate stratum corneum. Consequently, much lower contact impedance is obtained. Signal-noise ratio (SNR) of EMG signal shows a correlation coefficient of 0.9836 with height-width ratio of microstructures on the surface of metal dry bioelectrodes. Raw EMG signals recorded by metal dry bioelectrodes in 100 mT magnetic field show a high SNR up to 27.350, which is slightly higher than that of traditional Ag/AgCl wet bioelectrodes (26.689). By stationary wavelet transform (SWT) de-noising, noise interfused in raw EMG signals is suppressed effectively. Moreover, the de-noised EMG signal recorded using metal dry bioelectrodes processed in 100 mT magnetic field still remains a fairly high SNR.