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Droplet microfluidics has in recent years found a wide range of analytical and bioanalytical applications. In droplet microfluidics, the samples that are discretized into droplets within the devices are predominantly loaded through tubings, but such tubing-based sample loading has drawbacks such as limited scalability for processing many samples, difficulty for automation, and sample wastage. While advances in autosamplers have alleviated some of these drawbacks, sample loading that can instead obviate tubings offers a potentially promising alternative but has been underexplored. To fill the gap, we introduce herein a droplet device that features a new Tubing Eliminated Sample Loading Interface (TESLI). TESLI integrates a network of programmable pneumatic microvalves that regulate vacuum and pressure sources so that successive sub-microliter samples can be directly spotted onto the open-to-atmosphere TESLI inlet, vacuumed into the device, and pressurized into nanoliter droplets within the device with minimal wastage. The same vacuum and pressure regulation also endows TESLI with cleaning and sample switching capabilities, thus enabling scalable processing of many samples in succession. Moreover, we implement a pair of TESLIs in our device to parallelize and alternate their operation as means to minimizing idle time. For demonstration, we use our device to successively process 44 samples into droplets—a number that can further scale. Our results demonstrate the feasibility of tubing-free sample loading and a promising approach for advancing droplet microfluidics. [ABSTRACT FROM AUTHOR]

In the twenty-first century, the collaboration of control engineering and the healthcare sector has matured to some extent; however, the future will have promising opportunities, vast applications, and some challenges. Due to advancements in processing speed, the closed-loop administration of drugs has gained popularity for critically ill patients in intensive care units and routine life such as personalized drug delivery or implantable therapeutic devices. For developing a closed-loop drug delivery system, the control system works with a group of technologies like sensors, micromachining, wireless technologies, and pharmaceuticals. Recently, the integration of artificial intelligence techniques such as fuzzy logic, neural network, and reinforcement learning with the closed-loop drug delivery systems has brought their applications closer to fully intelligent automatic healthcare systems. This review's main objectives are to discuss the current developments, possibilities, and future visions in closed-loop drug delivery systems, for providing treatment to patients suffering from chronic diseases. It summarizes the present insight of closed-loop drug delivery/therapy for diabetes, gastrointestinal tract disease, cancer, anesthesia administration, cardiac ailments, and neurological disorders, from a perspective to show the research in the area of control theory. [ABSTRACT FROM AUTHOR]

Label-free and gentle separation of cell stages with desired target properties from mixed stage populations are a major research task in modern biotechnological cultivation process and optimization of micro algae. The reported microfluidic sorter system (MSS) allows the subsequent investigation of separated subpopulations. The implementation of a viability preserving MSS is shown for separation of late stage 1 Haematococcus pluvialis (HP) cells form a mixed stage population. The MSS combines a three-step flow focusing unit for aligning the cells in single file transportation mode at the center of the microfluidic channel with a pure hydrodynamic sorter structure for cell sorting. Lateral displacement of the cells into one of the two outlet channels is generated by piezo-actuated pump chambers. In-line decision making for sorting is based on a user-definable set of image features and properties. The reported MSS significantly increased the purity of target cells in the sorted population (94%) in comparison to the initial mixed stage population (19%). [ABSTRACT FROM AUTHOR]

In this article, simple two-steps process for the synthesis of silicon nanoparticles (Si NPs) from river sand of Bangladesh and application of the synthesized Si NPs for the improvement of the performance of the metal oxide heterojunction solar cells (HJSCs) have been investigated. A modified aluminothermic reaction was performed to extract highly pure silicon from sand. Later, ultrasonication on the extracted silicon in hydrofluoric acid (HF) was done to synthesis Si NPs from extracted Si. Afterward, the prepared Si NPs were used to dope CuO absorber for the fabrication of CuO/ZnO heterojunction solar cell. Properties of extracted Si and its effect after doping in copper oxide (CuO) were studied by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), X-ray Fluorescence (XRF), Fourier Transform Infrared Rays (FTIR), UV-Vis Spectroscopy, Raman and Photovoltaic study. Experimental results indicate that the extracted Si is polycrystalline in nature. The optical absorbance of CuO was enhanced significantly as a result of Si NPs doping and consequently, photoconversion efficiency was found to enhance more than 30% when Si NPs doped CuO was used in the Al/Si NP-CuO/ZnO/FTO heterostructure as a solar cell. This all spin-coated heterojunction solar cell showed a photoconversion efficiency of 1.16%. The photovoltaic responses reveal that the prepared Si NPs can be utilized for the improvement of the performance of HJSCs. This study on modified aluminothermically extracted Si NPs provide valuable insight and easy route for the preparation of Si NPs from sand and its applications in photovoltaic technology. [ABSTRACT FROM AUTHOR]

Isomotive dielectrophoresis (isoDEP) is a unique electric field such that the gradient of the field-squared (∇ E rms 2 ) is constant, resulting a uniform dielectrophoretic force. The current status of isoDEP is presented in this review, and we will highlight the progress that has been achieved over the past 60 years in various avenues of isoDEP since H.A. Pohl initially described its premise. This article will discuss its applications and describe the various configurations of generating an isomotive force. Since H.A. Pohl introduced the theory of isoDEP, numerous authors have implemented isoDEP as a tool for the manipulation, sorting, separation, and characterization of polarizable particles without the need for biochemical labels or other bioengineered tagging. The growing field of microfluidics and electrokinetics has renewed interest in isoDEP, particularly for analytical characterization or separation of particles. Recent work has demonstrated that isoDEP can address some unmet needs for biomedical applications including single-cell analysis; moreover, advances in throughput as well as combining characterization and separation simultaneously will add significant value to isoDEP. [ABSTRACT FROM AUTHOR]

The multi-disciplinary field of microfluidics has the potential to provide solutions to a diverse set of problems. It offers the advantages of high-throughput, continuous, rapid and expeditious analysis requiring minute quantities of sample. However, even as this field has yielded many mass-manufacturable and cost-efficient point-of-care devices, its direct and practical applications into the field of disease diagnostics still remain limited and largely overlooked by the industry. This review focuses on the phenomenon of hydrodynamic focusing and its potential to materialize solutions for appropriate diagnosis and prognosis. The study aims to look beyond its intended cytometric applications and focus on unambiguous disease detection, monitoring, drug delivery, studies conducted on DNA and highlight the instances in the scientific literature that have proposed such approach. [ABSTRACT FROM AUTHOR]

Recent advances in microfluidics technology can significantly benefit engineering and science research. Through integration with current optical tools like the optical/confocal microscope, the 3D printing, the soft lithography, and the lithography–etching, microfluidic pore model offers a direct and visual way to study the process of geological related pore-scale transport phenomena. In this paper, recent progress of microfluidic pore model mimicking the geological porous media are discussed, which can apply on many disciplines such as environmental, petroleum engineering and geosciences. The purpose of this review is to highlight the significant features of microfluidic pore model application in geological porous medium pertaining research, as well as to provide engineer/scientist an overview of materials and fabrication methods to manufacture micromodels. Furthermore, the outlook of intensively using micromodel as a multifunction real-time analysis tool is proposed to help the reader to enhance their understanding of pore-scale transport phenomena related to geological porous medium. Also, potential critical issues of micromodels in both research and teaching are discussed. The overall role of this review for microfluidic application is intended to provide benefits to professors, students, and other scientists not only in research but also in teaching fields. [ABSTRACT FROM AUTHOR]

This review aims at focusing on the use of microneedles (MNs) as an emerging novel drug delivery carrier for an effective treatment in diabetic patients. There are many limitations in various modes of delivery such as oral, subcutaneous, nasal, and other modes which cause pain and have many other side effects. Hence, this drug delivery research has found to have tremendous potential in combining both the diagnostic and therapeutic elements, thus treating diabetes in a better way. Most glucose-sensing techniques and conventional insulin therapies are engaged in the transfer of physical entities through the skin. MN- based drug delivery system can accomplish in an noninvasive or minimally invasive manner which can be an add on advantage towards pain-free administration, easy handling, discrete, continuous as well as providing a controlled release system. Hence, the review addresses on the current advancement of this bioengineered system like MNs, constituting a "smart" system specifically for autonomous diabetes therapy. [ABSTRACT FROM AUTHOR]

Digestive diseases are a major burden for society and healthcare systems, and with an aging population, the importance of their effective management will become critical. Healthcare systems worldwide already struggle to insure quality and affordability of healthcare delivery and this will be a significant challenge in the midterm future. Wireless capsule endoscopy (WCE), introduced in 2000 by Given Imaging Ltd., is an example of disruptive technology and represents an attractive alternative to traditional diagnostic techniques. WCE overcomes conventional endoscopy enabling inspection of the digestive system without discomfort or the need for sedation. Thus, it has the advantage of encouraging patients to undergo gastrointestinal (GI) tract examinations and of facilitating mass screening programmes. With the integration of further capabilities based on microrobotics, e.g. active locomotion and embedded therapeutic modules, WCE could become the key-technology for GI diagnosis and treatment. This review presents a research update on WCE and describes the state-of-the-art of current endoscopic devices with a focus on research-oriented robotic capsule endoscopes enabled by microsystem technologies. The article also presents a visionary perspective on WCE potential for screening, diagnostic and therapeutic endoscopic procedures. [ABSTRACT FROM AUTHOR]

Liposomes are well-known cell simulators and are currently studied as drug delivery systems, for a targeted delivery of higher drug concentrations, in specific cells. Novel biophotonic techniques for manipulation and characterization of liposomes have been developed; among which are optical tweezers. In our work, we demonstrate a novel use of line optical tweezers to manipulate and cause liposome deformations. Optical forces induce tension on liposomes, which are stretched along the line optical trap. The method of dielectrophoresis, combined with optical tweezers, was used to measure the exerted optical forces. As a consequence, in the case of reversible liposome deformations, the value of the shear and bending moduli of liposomes was calculated. We anticipate that the selective manipulation of liposomes will help us toward a better understanding of the cellular–liposome interactions. Studying the biomechanical properties of liposomes will provide an insight into the mechanical behavior of individual living cells, which have recently been implicated in many aspects of human physiology and patho-physiology. The biomechanical properties of cells (i.e. deformability, stiffness and elasticity) can be useful biomarkers for various disease processes and changes of the cell state. [ABSTRACT FROM AUTHOR]

A two dimensional rectangular microchannel with circular micropillars was modeled in the presence of an electric field. Continuity and Navier-Stokes equations were solved along with convection-diffusion equation using finite element method. Reaction phenomenon was applied via a partial differential equation on the reaction surfaces and electric force was added as a source term to the transport equations. Velocity, concentration and electric potential distributions were obtained, with the aid of which, capture efficiency and average surface concentration of reaction surfaces were calculated. To ameliorate the reaction rate, different designs of reaction surfaces were investigated; the designs with four, five and six micropillars. The importance of flow specifications in the microreactor was inspected through varying a non-dimensionalized parameter, i.e. Peclet number. The electric field was implemented on the microchannel's upper and lower walls and its effect on the performance of the device was studied. Different voltages were applied and the results were compared to the case without an electric field. The efficiency of the microreactors was observed to be dependent on the geometry of the reaction surfaces as well as the inlet velocity magnitude of the bulk flow and the electric field magnitude. It was observed that by increasing the inlet velocity, the flow regime became convection dominant. Therefore, the diffusion effect was minimized and the efficiency of the device lessened. It was also observed that in all cases, the presence of the electric field enhanced the reaction efficiency by pushing the flow towards the reaction surfaces. The six micropillar arrangement was shown to be the optimum design by analyzing both capture efficiency and average surface concentration. [ABSTRACT FROM AUTHOR]

Personalized medicine - healthcare based on individual genetic variation - has the potential to transform the way healthcare is delivered to patients. The promise of personalized medicine has been predicated on the predictive and diagnostic power of genomic and proteomic biomarkers. Biomarker screening may help improve health outcomes, for example, by identifying individuals' susceptibility to diseases and predicting how patients will respond to drugs. Microfluidic droplet technology offers an exciting opportunity to revolutionize the accessibility of personalized medicine. A framework for the role of droplet microfluidics in biomarker detection can be based on two main themes. Emulsion-based microdroplet platforms can provide new ways to measure and detect biomolecules. In addition, microdroplet platforms facilitate high-throughput screening of biomarkers. Meanwhile, surface-based droplet platforms provide an opportunity to develop miniaturized diagnostic systems. These platforms may function as portable benchtop environments that dramatically shorten the transition of a benchtop assay into a point-of-care format. [ABSTRACT FROM AUTHOR]

By simultaneously subjecting microbial cells to high amplitude pulsed electric fields and flash heating of the cell suspension fluid, effective release of intracellular contents was achieved. The synergistic effect of the applied electric field and elevated temperature on cell lysis in a flow-through device was demonstrated for Gram-negative and Gram-positive bacteria, and Mycobacterium species. The resulting lysate is suitable for downstream nucleic acid amplification and detection without requiring further preparation. The lysis chamber employs surface enhanced blocking electrodes which possess an etched micro-structured surface and a thin layer of dielectric metal oxide which provides a large effective area and blocks transmission of electrical current. The surface enhanced blocking electrodes enable simultaneous suppression of the rapid onset of electric field screening in the bulk of the cell suspension medium and avoidance of undesired electrochemical processes at the electrode-electrolyte interface. In addition the blocking layer ensures the robustness of the cell lysis device in applications involving prolonged flow-through processing of the microbial cells. [ABSTRACT FROM AUTHOR]

Background: Microelectrode dieletrophoresis capture of live cells has been explored in animal and cellular models ex-vivo. Currently, there is no clinical data available regarding the safety and efficacy of dielectrophoresis (DEP) buffers and microcurrent manipulation in humans, despite copious pre-clinical studies suggesting its safety. The purpose of this study was to determine if DEP isolation of SVF using minimal manipulation methods is safe and efficacious for use in humans using the hand lipotransfer model. Methods: Autologous stromal vascular fraction cells (SVF) were obtained from lipoaspirate by collagenase digestion and centrifugation. The final mixture of live and dead cells was further processed using a custom DEP microelectrode array and microcurrent generator to isolate only live nucleated cells. Lipotransfer was completed using fat graft enhanced with either standard processed SVF (control) versus DEP filtered SVF (experimental). Spectral photography, ultrasound and biometric measurements were obtained at post operatively days 1, 4, 7, 14, 30, 60 and 90. Results: The DEP filter was capable of increasing SVF viability counts from 74.3 ± 2.0% to 94.7 ± 2.1%. Surrogate markers of inflammation (temperature, soft tissue swelling, pain and diminished range of motion) were more profound on the control hand. Clinical improvement in hand appearance was appreciated in both hands, though the control hand exclusively sustained late phase erosive skin breaks on post operative day 7. No skin breaks were appreciated on the DEP-SVF treated hand. Early fat engraftment failure was noted on the control hand thenar web space at 3 months post surgery. Discussion: No immediate hypersensitivity or adverse reaction was appreciated with the DEP-SVF treated hand. In fact, the control hand experienced skin disruption and mild superficial cellulitis, whereas the experimental hand did not experience this complication, suggesting a possible "protective" effect with DEP filtered SVF. Late ultrasound survey revealed larger and more frequent formation of oil cysts in the control hand, also suggesting greater risk of engraftment failure with standard lipotransfer. Conclusion: Clinical DEP appears safe and efficacious for human use. The DEP microelectrode array was found to be versatile and robust in efficiently isolating live SVF cells from dead cells and cellular debris in a time sensitive clinical setting. [ABSTRACT FROM AUTHOR]

Efficient electroporation of cells in physical contact induces cell fusion, and this process is known as electrofusion. It has been shown that appropriate hypotonic treatment of cells before the application of electric pulses can cause a significant increase in electrofusion efficiency. First, the amplitudes of the electric field were determined spectrofluorometrically, where sufficient permeabilization in hypotonic buffer occurred for B16-F1 and CHO cells. In further electrofusion experiments 14 +/- 4% of fused cells for B16-F1 and 6 +/- 1% for CHO was achieved. These electrofusion efficiencies, determined by double staining and fluorescence microcopy, are comparable to those of other published studies. It was also confirmed that successful electroporation does not necessarily guarantee high electrofusion efficiency due to biological factors involved in the electrofusion process. Furthermore, not only the extension of electrofusion but also cell survival depends on the cell line used. Further studies are needed to improve overall cell survival after electroporation in hypotonic buffer, which was significantly reduced, especially for B16-F1 cells. Another contribution of this report is the description of a simple modification of the adherence method for formation of spontaneous cell contact, while cells preserve their spherical shape. [ABSTRACT FROM AUTHOR]

In this report we investigate the alterations of the dielectric properties of the plasma membrane caused by the infection of cultured fibroblasts with murine polyomavirus. The approach consists in a well-established dielectric spectroscopy technique, electrorotation, which has been successfully used in our laboratory to study the alterations of the plasma membrane of cells exposed to various forms of stress. The response to viral proliferation was time dependent as shown by evaluation of the de novo synthesis of viral DNA. This response was paralleled by gradual damage of the membrane evidenced by alteration of the dielectric parameters, specific capacitance and conductance. The electrorotation results show a reduced effect on the dielectric properties of the membrane when infection is carried out in the presence of a natural oil (MEX). In this case a drastic reduction in viral DNA synthesis was also monitored, thus indicating an antiviral action of this product. [ABSTRACT FROM AUTHOR]

Neem oil is a natural product obtained from the seeds of the tree Azadirachta indica. In this report, we investigate the alterations of the biophysical properties of the plasma membrane caused by treatment with the nonterpenoid fraction of neem oil that we defined as methanolic extract (MEX). The dose-response effect was evaluated and a MEX-dependent cytoxicity evidenced. The effect of MEX on the plasma membrane was studied by a well-established dielectric spectroscopy technique: electrorotation, which allows single-cell analysis. Our results show a structural/functional alteration of the plasma membrane with an evident increase of specific capacitance and conductance. The biological implications of this effect are discussed. [ABSTRACT FROM AUTHOR]

Manipulation of cells or bio-targets is required in a variety of biological, diagnostic and therapeutic applications. In this paper, we present a novel magnetic separator for magnetic bead labeled-target sorting in microfluidic systems. This micro magnetic separator includes 3D micro copper coil, soft magnetic tips and FeNi wires. The magnetic tips and FeNi wires are first simulated and optimized by MagNet software to increase the magnetic force exerted on magnetic beads, and fabricated by microfabrication technology. The experiment results show the sorting ratio of the magnetic beads can be up to 92.5% with the current of 200 mA and the flow rate of 5 µL/min. The maximum sorting ratio can reach 78.4% for 100 CFU/mL E. coli O157:H7 sample with the current of 200 mA and the flow rate of 0.5 µL/min. On account of the miniaturization, high sorting efficiency, low excitation current, high level of detection automation and easy integration with micro magnetic sensor, this micro magnetic separation system can be a potential application in bio-target sorting and detecting. [ABSTRACT FROM AUTHOR]

Background: Custom synthesized DNA is in high demand for synthetic biology applications. However, current technologies to produce these sequences using assembly from DNA oligonucleotides are costly and labor-intensive. The automation and reduced sample volumes afforded by microfluidic technologies could significantly decrease materials and labor costs associated with DNA synthesis. The purpose of this study was to develop a gene assembly protocol utilizing a digital microfluidic device. Toward this goal, we adapted bench-scale oligonucleotide assembly methods followed by enzymatic error correction to the Mondrian™ digital microfluidic platform. Results: We optimized Gibson assembly, polymerase chain reaction (PCR), and enzymatic error correction reactions in a single protocol to assemble 12 oligonucleotides into a 339-bp double- stranded DNA sequence encoding part of the human influenza virus hemagglutinin (HA) gene. The reactions were scaled down to 0.6-1.2 μL. Initial microfluidic assembly methods were successful and had an error frequency of approximately 4 errors/kb with errors originating from the original oligonucleotide synthesis. Relative to conventional benchtop procedures, PCR optimization required additional amounts of MgCl2, Phusion polymerase, and PEG 8000 to achieve amplification of the assembly and error correction products. After one round of error correction, error frequency was reduced to an average of 1.8 errors kb− 1. Conclusion: We demonstrated that DNA assembly from oligonucleotides and error correction could be completely automated on a digital microfluidic (DMF) platform. The results demonstrate that enzymatic reactions in droplets show a strong dependence on surface interactions, and successful on-chip implementation required supplementation with surfactants, molecular crowding agents, and an excess of enzyme. Enzymatic error correction of assembled fragments improved sequence fidelity by 2-fold, which was a significant improvement but somewhat lower than expected compared to bench-top assays, suggesting an additional capacity for optimization. [ABSTRACT FROM AUTHOR]