Showing papers in "Biomedical Microdevices in 2016"

Miniaturized implantable sensors for in vivo localized temperature measurements in mice during cold exposure.

Abstract: We report on in vivo temperature measurements performed in mice at two specific sites of interest in the animal body over a period of several hours. In particular, the aim of this work was to monitor mouse metabolism during cold exposure, and to record possible temperature differences between the body temperature measured in the abdomen and the temperature of the brown adipose tissue (BAT) situated in the interscapular area. This approach is of biological interest as it may help unravelling the question whether biochemical activation of BAT is associated with local increase in metabolic heat production. For that purpose, miniaturized thermistor sensors have been accurately calibrated and implanted in the BAT and in the abdominal tissue of mice. After 1 week of recovery from surgery, mice were exposed to cold (6 °C) for a maximum duration of 6 h and the temperature was acquired continuously from the two sensors. Control measurements with a conventional rectal probe confirmed good performance of both sensors. Moreover, two different mouse phenotypes could be identified, distinguishable in terms of their metabolic resistance to cold exposure. This difference was analyzed from the thermal point of view by computational simulations. Our simple physical model of the mouse body allowed to reproduce the global evolution of hypothermia and also to explain qualitatively the temperature difference between abdomen and BAT locations. While with our approach, we have demonstrated the importance and feasibility of localized temperature measurements on mice, further optimization of this technique may help better identify local metabolism variations.

Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium

Abstract: The vascular endothelium and shear stress are critical determinants of physiological hemostasis and platelet function in vivo, yet current diagnostic and monitoring devices do not fully incorporate endothelial function under flow in their assessment and, therefore, they can be unreliable and inaccurate. It is challenging to include the endothelium in assays for clinical laboratories or point-of-care settings because living cell cultures are not sufficiently robust. Here, we describe a microfluidic device that is lined by a human endothelium that is chemically fixed, but still retains its ability to modulate hemostasis under continuous flow in vitro even after few days of storage. This device lined with a fixed endothelium supports formation of platelet-rich thrombi in the presence of physiological shear, similar to a living arterial vessel. We demonstrate the potential clinical value of this device by showing that thrombus formation and platelet function can be measured within minutes using a small volume (0.5 mL) of whole blood taken from subjects receiving antiplatelet medications. The inclusion of a fixed endothelial microvessel will lead to biomimetic analytical devices that can potentially be used for diagnostics and point-of-care applications.

Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications.

Abstract: The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print-head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 μm – 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 μm – 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi-layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0–40 m/min) and corresponding flow rates (1–30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

A concentration gradient generator on a paper-based microfluidic chip coupled with cell culture microarray for high-throughput drug screening.

Abstract: Inspired by the paper platforms for 3-D cell culture, a paper-based microfluidic device containing drug concentration gradient was designed and constructed for investigating cell response to drugs based on high throughput analysis. This drug gradient generator was applied to generate concentration gradients of doxorubicin (DOX) as the model drug. HeLa cells encapsulated in collagen hydrogel were incubated in the device reservoirs to evaluate the cell viability based on the controlled release of DOX spatially. It was demonstrated that drug diffusion through the paper fibers created a gradient of drug concentration, which influenced cell viability. This drug screening platform has a great opportunity to be applied for drug discovery and diagnostic studies with simultaneous and parallel tests of drugs under various gradient concentrations.

A novel design for passive misscromixers based on topology optimization method.

Abstract: In this paper, a series of novel passive micromixers, called topological micromixers with reversed flow (TMRFX), are proposed. The reversed flow in the microchannels can enhance chaotic advection and produce better mixing performance. Therefore the maximum of reversed flow is chosen as the objective function of the topology optimization problem. Because the square-wave unit is easier to fabricate and have better mixing performance than many other serpentine micromixers, square-wave structure becomes the original geometry structure. By simulating analysis, the series of TMRFX, namely TMRF, TMRF0.75, TMRF0.5, TMRF0.25, mix better than the square-wave micromixer at various Reynolds numbers (Re), but pressure drops of TMRFX are much higher. Lots of intensive numerical simulations are conducted to prove that TMRF and TMRF0.75 have remarkable advantages on mixing over other micromixers at various Re. The mixing performance of TMRF0.75 is similar to TMRF's. What's more, TMRF have a larger pressure drop than TMRF0.75, which means that TMRF have taken more energy than TMRF0.75. For a wide range of Re (Re ≤ 0.1 and Re ≥ 10), TMRF0.75 delivers a great performance and the mixing efficiency is greater than 95 %. Even in the range of 0.1-10 for the Re, the mixing efficiency of TMRF0.75 is higher than 85 %.

Design and characteristics evaluation of a novel teleoperated robotic catheterization system with force feedback for vascular interventional surgery.

Abstract: In this paper, we proposed a novel master-slave robotic catheterization system with force feedback for VIS (Vascular Interventional Surgery). The force feedback to the operator on the master side is the key factor to improve the safety during VIS. The developed system used the MR (magneto rheological) fluid to realize force feedback, and it used the developed multidimensional monitoring interface to realize the visualization of force feedback, the developed multidimensional monitoring interface can monitor the motion information of the catheter and contact force between catheter tip or side wall and blood vessel wall, and the motion data of the catheter was collected and generated diagram for reference to surgeon. We have developed a force sensor array to detect the contact force between catheter tip or side wall and blood vessel wall. The force information was detected by the developed contact force sensor array when the catheter contacted with the blood vessel. The force feedback and multidimensional information monitoring interface evaluation experiments were done, the tracking characteristic evaluation experiments were also carried out, the experimental results indicated that the developed novel robotic catheterization system with force feedback and visualization of force feedback is effective for VIS, it can improve the safety during VIS.

Polyethersulfone improves isothermal nucleic acid amplification compared to current paper-based diagnostics

Abstract: Devices based on rapid, paper-based, isothermal nucleic acid amplification techniques have recently emerged with the potential to fill a growing need for highly sensitive point-of-care diagnostics throughout the world. As this field develops, such devices will require optimized materials that promote amplification and sample preparation. Herein, we systematically investigated isothermal nucleic acid amplification in materials currently used in rapid diagnostics (cellulose paper, glass fiber, and nitrocellulose) and two additional porous membranes with upstream sample preparation capabilities (polyethersulfone and polycarbonate). We compared amplification efficiency from four separate DNA and RNA targets (Bordetella pertussis, Chlamydia trachomatis, Neisseria gonorrhoeae, and Influenza A H1N1) within these materials using two different isothermal amplification schemes, helicase dependent amplification (tHDA) and loop-mediated isothermal amplification (LAMP), and traditional PCR. We found that the current paper-based diagnostic membranes inhibited nucleic acid amplification when compared to membrane-free controls; however, polyethersulfone allowed for efficient amplification in both LAMP and tHDA reactions. Further, observing the performance of traditional PCR amplification within these membranes was not predicative of their effects on in situ LAMP and tHDA. Polyethersulfone is a new material for paper-based nucleic acid amplification, yet provides an optimal support for rapid molecular diagnostics for point-of-care applications.

Ultra-miniature ultra-compliant neural probes with dissolvable delivery needles: design, fabrication and characterization

Abstract: Stable chronic functionality of intracortical probes is of utmost importance toward realizing clinical application of brain-machine interfaces. Sustained immune response from the brain tissue to the neural probes is one of the major challenges that hinder stable chronic functionality. There is a growing body of evidence in the literature that highly compliant neural probes with sub-cellular dimensions may significantly reduce the foreign-body response, thereby enhancing long term stability of intracortical recordings. Since the prevailing commercial probes are considerably larger than neurons and of high stiffness, new approaches are needed for developing miniature probes with high compliance. In this paper, we present design, fabrication, and in vitro evaluation of ultra-miniature (2.7 μm x 10 μm cross section), ultra-compliant (1.4 × 10-2 μN/μm in the axial direction, and 2.6 × 10-5 μN/μm and 1.8 × 10-6 μN/μm in the lateral directions) neural probes and associated probe-encasing biodissolvable delivery needles toward addressing the aforementioned challenges. The high compliance of the probes is obtained by micron-scale cross-section and meandered shape of the parylene-C insulated platinum wiring. Finite-element analysis is performed to compare the strains within the tissue during micromotion when using the ultra-compliant meandered probes with that when using stiff silicon probes. The standard batch microfabrication techniques are used for creating the probes. A dissolvable delivery needle that encases the probe facilitates failure-free insertion and precise placement of the ultra-compliant probes. Upon completion of implantation, the needle gradually dissolves, leaving behind the ultra-compliant neural probe. A spin-casting based micromolding approach is used for the fabrication of the needle. To demonstrate the versatility of the process, needles from different biodissolvable materials, as well as two-dimensional needle arrays with different geometries and dimensions, are fabricated. Further, needles incorporating anti-inflammatory drugs are created to show the co-delivery potential of the needles. An automated insertion device is developed for repeatable and precise implantation of needle-encased probes into brain tissue. Insertion of the needles without mechanical failure, and their subsequent dissolution are demonstrated. It is concluded that ultra-miniature, ultra-compliant probes and associated biodissolvable delivery needles can be successfully fabricated, and the use of the ultra-compliant meandered probes results in drastic reduction in strains imposed in the tissue as compared to stiff probes, thereby showing promise toward chronic applications.

Protein patterning by microcontact printing using pyramidal PDMS stamps.

Abstract: Micro-contact printing, μCP, is a well-established soft-lithography technique for printing biomolecules. μCP uses stamps made of Poly(dimethylsiloxane), PDMS, made by replicating a microstructured silicon master fabricated by semiconductor manufacturing processes. One of the problems of the μCP is the difficult control of the printing process, which, because of the high compressibility of PDMS, is very sensitive to minute changes in the applied pressure. This over-sensitive response leads to frequent and/or uncontrollable collapse of the stamps with high aspect ratios, thus decreasing the printing accuracy and reproducibility. Here we present a straightforward methodology of designing and fabricating PDMS structures with an architecture which uses the collapse of the stamp to reduce, rather than enlarge the variability of the printing. The PDMS stamp, organized as an array of pyramidal micro-posts, whose ceiling collapses when pressed on a flat surface, replicates the structure of the silicon master fabricated by anisotropic wet etching. Upon application of pressure, depending on the size of, and the pitch between, the PDMS pyramids, an air gap is formed surrounding either the entire array, or individual posts. The printing technology, which also exhibits a remarkably low background noise for fluorescence detection, may find applications when the clear demarcation of the shapes of protein patterns and the distance between them are critical, such as microarrays and studies of cell patterning.

A novel screen-printed microfluidic paper-based electrochemical device for detection of glucose and uric acid in urine.

Abstract: A novel screen-printed microfluidic paper-based analytical device with all-carbon electrode-enabled electrochemical assay (SP-ACE-EC-μPAD) has been developed. The fabrication of these devices involved wax screen-printing, which was simple, low-cost and energy-efficient. The working, counter and reference electrodes were screen-printed using carbon ink on the patterned paper devices. Different wax screen-printing processes were examined and optimized, which led to an improved method with a shorter heating time (~5 s) and a lower heating temperature (75 °C). Different printing screens were examined, with a 300-mesh polyester screen yielding the highest quality wax screen-prints. The carbon electrodes were screen-printed on the μPADs and then examined using cyclic voltammetry. The analytical performance of the SP-ACE-EC-μPADs for the detection of glucose and uric acid in standard solutions was investigated. The results were reproducible, with a linear relationship [R2 = 0.9987 (glucose) or 0.9997 (uric acid)] within the concentration range of interest, and with detection limits as low as 0.35 mM (glucose) and 0.08 mM (uric acid). To determine the clinical utility of the μPADs, chronoamperometry was used to analyze glucose and uric acid in real urine samples using the standard addition method. Our devices were able to detect the analytes of interest in complex real-world biological samples, and have the potential for use in a wide variety of applications.

Characterization of tight junction disruption and immune response modulation in a miniaturized Caco-2/U937 coculture-based in vitro model of the human intestinal barrier.

Abstract: A microfluidic-based dynamic in vitro model of the human intestinal barrier has been constructed and characterized. The intestinal epithelial monolayer was mimicked by culturing caco-2 cells on a porous membrane in a double-layered microfluidic chip and interfaced with a co-culture of U937 as a model of immune responsive cells. The physiological flow was also mimicked by a continuous perfusion of culture media from the apical and basolateral side of the porous membrane. This dynamic "in vivo-like" environment maintains a continuous supply of cell nutrient and waste removal and create mechanical shear stress within the physiological ranges which promotes uniform cell growth and tight junction formation. The monolayer permeability to soluble ion changes after treating with LPS, and TNF α as indicated by the reduction of the TEER value. In addition, the immune competent caco-2/U937-based model allowed the investigating the role of the epithelial layer as a protection barrier to biological hazards as indicated by the suppressing of the pro-inflammatory cytokine expression.

A pumpless microfluidic device driven by surface tension for pancreatic islet analysis

Abstract: We present a novel pumpless microfluidic array driven by surface tension for studying the physiology of pancreatic islets of Langerhans. Efficient fluid flow in the array is achieved by surface tension-generated pressure as a result of inlet and outlet size differences. Flow properties are characterized in numerical simulation and further confirmed by experimental measurements. Using this device, we perform a set of biological assays, which include real-time fluorescent imaging and insulin secretion kinetics for both mouse and human islets. Our results demonstrate that this system not only drastically simplifies previously published experimental protocols for islet study by eliminating the need for external pumps/tubing and reducing the volume of solution consumption, but it also achieves a higher analytical spatiotemporal resolution due to efficient flow exchanges and the extremely small volume of solutions required. Overall, the microfluidic platform presented can be used as a potential powerful tool for understanding islet physiology, antidiabetic drug development, and islet transplantation.

Facile and cost-effective production of microscale PDMS architectures using a combined micromilling-replica moulding (μMi-REM) technique

Abstract: We describe a cost-effective and simple method to fabricate PDMS-based microfluidic devices by combining micromilling with replica moulding technology. It relies on the following steps: (i) microchannels are milled in a block of acrylic; (ii) low-cost epoxy adhesive resin is poured over the milled acrylic block and allowed to cure; (iii) the solidified resin layer is peeled off the acrylic block and used as a mould for transferring the microchannel architecture onto a PDMS layer; finally (iv) the PDMS layer is plasma bonded to a glass surface. With this method, microscale architectures can be fabricated without the need for advanced technological equipment or laborious and time-consuming intermediate procedures. In this manuscript, we describe and validate the microfabrication procedure, and we illustrate its applicability to emulsion and microbubble production.

Human pancreatic stellate cells modulate 3D collagen alignment to promote the migration of pancreatic ductal adenocarcinoma cells

Abstract: A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the ability for cancer cells to aggressively infiltrate and navigate through a dense stroma during the metastatic process. Key features of the PDAC stroma include an abundant population of activated pancreatic stellate cells (PSCs) and highly aligned collagen fibers; however, important questions remain regarding how collagen becomes aligned and what the biological manifestations are. To better understand how PSCs, aligned collagen, and PDAC cells might cooperate during the transition to invasion, we utilized a microchannel-based in vitro tumor model and advanced imaging technologies to recreate and examine in vivo-like heterotypic interactions. We found that PSCs participate in a collaborative process with cancer cells by orchestrating the alignment of collagen fibers that, in turn, are permissive to enhanced cell migration. Additionally, direct contact between PSCs, collagen, and PDAC cells is critical to invasion and co-migration of both cell types. This suggests PSCs may accompany and assist in navigating PDAC cells through the stromal terrain. Together, our data provides a new role for PSCs in stimulating the metastatic process and underscores the importance of collagen alignment in cancer progression.

Characterizing tissue stiffness at the tip of a rigid needle using an opto-mechanical force sensor.

Abstract: We present a novel device that allows the user to measure the Young Modulus of a material at the opening of a 5 mm diameter needle. The device relies on a miniaturized cantilever spring mounted at the end of the needle and interrogated via Fabry-Perot optical fiber interferometry. The probe is repetitively brought in and out of contact with the sample at the end of the needle by means of a steel cable that is controlled via a piezoelectric actuator located at the proximal end. We demonstrate the ability of our device to detect and quantify layers of varying stiffness during needle insertion in a gelatin phantom and to successfully locate tissue boundaries in bovine liver tissue embedded in gelatin.

Microfluidic advances in phenotypic antibiotic susceptibility testing

Abstract: A strong natural selection for microbial antibiotic resistance has resulted from the extensive use and misuse of antibiotics Though multiple factors are responsible for this crisis, the most significant factor - widespread prescription of broad-spectrum antibiotics - is largely driven by the fact that the standard process for determining antibiotic susceptibility includes a 1-2-day culture period, resulting in 48-72 h from patient sample to final determination Clearly, disruptive approaches, rather than small incremental gains, are needed to address this issue The field of microfluidics promises several advantages over existing macro-scale methods, including: faster assays, increased multiplexing, smaller volumes, increased portability for potential point-of-care use, higher sensitivity, and rapid detection methods This Perspective will cover the advances made in the field of microfluidic, phenotypic antibiotic susceptibility testing (AST) over the past two years Sections are organized based on the functionality of the chip - from simple microscopy platforms, to gradient generators, to antibody-based capture devices Microfluidic AST methods that monitor growth as well as those that are not based on growth are presented Finally, we will give our perspective on the major hurdles still facing the field, including the need for rapid sample preparation and affordable detection technologies

An ultrasensitive label free nanobiosensor platform for the detection of cardiac biomarkers

Abstract: We report the fabrication of a label free nano biosensor platform comprising single nanofiber that is derived out of multi-walled carbon nanotubes (MWCNTs) embedded SU-8 photoresist, for the detection of three important human cardiac biomarkers viz., myoglobin (Myo), cardiac Troponin I (cTn I) and Creatine Kinase-MB (CK-MB). These composite nanofibers were synthesized using electrospinning process. Single nanofibers were aligned between pairs of electrodes in-situ during the electrospinning process. The target proteins were detected using chemiresistive detection methodology. Each biomarker was detected using a specific, single, aligned nanofiber, functionalized with its corresponding monoclonal antibody. Chemiresistive detection involves measuring the change in conductance of the functionalized nanofibers upon the binding of the targeted antigen. The minimum detection limits of Myo, CK-MB and cTn I were experimentally found out to be as low as 6, 20 and 50 fg/ml respectively. No response was observed when the nanofibers were exposed to a non-specific protein, demonstrating excellent specificity to the targeted detection. These MWCNTs embedded SU-8 nanofibers based nanobiosensor platform shows great promise in the detection of cardiac markers and other proteins as they have fast response time, high sensitivity and good specificity.

Low-cost, real-time, continuous flow PCR system for pathogen detection

Abstract: In this paper, we present a portable and low cost point-of-care (POC) PCR system for quantitative detection of pathogens. Our system is based on continuous flow PCR which maintains fixed temperatures zones and pushes the PCR solution between two heated areas allowing for faster heat transfer and as a result, a faster PCR. The PCR system is built around a 46.0 mm × 30.9 mm × 0.4 mm disposable thermoplastic chip. In order to make the single-use chip economically viable, it was manufactured by hot embossing and was designed to be compatible with roll-to-roll embossing for large scale production. The prototype instrumentation surrounding the chip includes two heaters, thermal sensors, and an optical system. The optical system allows for pathogen detection via real time fluorescence measurements. FAM probes were used as fluorescent reporters of the amplicons generated during the PCR. To demonstrate the function of the chip, two infectious bacteria targets were selected: Chlamydia trachomatis and Escherichia coli O157:H7. For both bacteria, the limit of detection of the system was determined, PCR efficiencies were calculated, and different flow velocities were tested. We have demonstrated successful detection for these two bacterial pathogens highlighting the versatility and broad utility of our portable, low-cost, and rapid PCR diagnostic device.

An integrated microfluidic PCR system with immunomagnetic nanoparticles for the detection of bacterial pathogens

Abstract: There is growing interest in rapid microbial pre-concentration methods to lower the detection limit of bacterial pathogens of low abundance in samples. Here, we report an integrated microfluidic PCR system that enables bacterial cells of interest in samples to be concentrated prior to PCR. It consists of two major compartments: a preconcentration chamber for the immunomagnetic separation of bacterial cells, and a PCR chamber for the DNA amplification of the concentrated cells. We demonstrate the feasibility of the system for the detection of microbial pathogens by preconcentrating the human pathogen Escherichia coli O157:H7, and also amplifying its DNA. The detection limit of E. coli O157:H7 in the PCR system is 1 × 103 CFU (colony forming unit)/mL. On-chip processing steps, including preconcentration and PCR steps, take less than two hours. Our system can serve as a rapid, specific, and quantitative platform for the detection of microbial pathogens in samples of large volume.

Manufacturing methods and applications of membranes in microfluidics

Abstract: Applications of membranes in microfluidics solved many thorny problems for analytical chemistry and bioscience, so that the use of membranes in microfluidics has been a topic of growing interest Many different examples have been reported, demonstrating the versatile use of membranes This work reviews a lot of applications of membranes in microfluidics Membranes in microfluidics for applications including chemical reagents detection, gas detection, drug screening, cell, protein, microreactor, electrokinetical fluid, pump and valve and fluid transport control and so on, have been analyzed and discussed In addition, the definition and basic concepts of membranes are summed up And the methods of manufacturing membranes in microfluidics are discussed This paper will provide a helpful reference to researchers who want to study applications of membranes in microfluidics

Simple and rapid sample preparation system for the molecular detection of antibiotic resistant pathogens in human urine

Abstract: Antibiotic resistance in urinary tract infections (UTIs) can cause significant complications without quick detection and appropriate treatment. We describe a new approach to capture, concentrate and prepare amplification-ready DNA from antibiotic resistant bacteria in human urine samples. Klebsiella pneumoniae NCTC13443 (bla CTX-M-15 positive) spiked into filtered human urine was used as a model system. Bacteria were captured using anion exchange diaethylaminoethyl (DEAE) magnetic microparticles and concentrated 200-fold within ~3.5 min using a custom, valve-less microfluidic chip. Eight samples were processed in parallel, and DNA was released using heat lysis from an integrated resistive heater. The crude cell lysate was used for real time Recombinase Polymerase Amplification (RPA) of the bla CTX-M-15 gene. The end to end processing time was approximately 15 min with a limit of detection of 1000 bacteria in 1 mL urine.

An integrated microfluidic chip for immunomagnetic detection and isolation of rare prostate cancer cells from blood

Abstract: The quantitative and qualitative analysis of circulating tumor cells (CTCs) has the potential to improve the clinical management of several cancers, including prostate cancer. As such, there is much interest in the isolation of CTCs from the peripheral blood of cancer patients. We report the design, fabrication, and proof-of-principle testing of an integrated permalloy-based microfluidic chip for immunomagnetic isolation of blood-borne prostate cancer cells using an antibody targeting prostate surface membrane antigen (PSMA). The preliminary results using spiked blood samples indicate that the proposed device is consistently capable of isolating prostate cancer cells with high sensitivity (up to 98 %) at clinically relevant low concentrations (down to 20 cells/mL) and an acceptable throughput (100 μL/min).

Controlled regular locomotion of algae cell microrobots

Abstract: Algae cells can be considered as microrobots from the perspective of engineering. These organisms not only have a strong reproductive ability but can also sense the environment, harvest energy from the surroundings, and swim very efficiently, accommodating all these functions in a body of size on the order of dozens of micrometers. An interesting topic with respect to random swimming motions of algae cells in a liquid is how to precisely control them as microrobots such that they swim according to manually set routes. This study developed an ingenious method to steer swimming cells based on the phototaxis. The method used a varying light signal to direct the motion of the cells. The swimming trajectory, speed, and force of algae cells were analyzed in detail. Then the algae cell could be controlled to swim back and forth, and traverse a crossroad as a microrobot obeying specific traffic rules. Furthermore, their motions along arbitrarily set trajectories such as zigzag, and triangle were realized successfully under optical control. Robotize algae cells can be used to precisely transport and deliver cargo such as drug particles in microfluidic chip for biomedical treatment and pharmacodynamic analysis. The study findings are expected to bring significant breakthrough in biological drives and new biomedical applications.

A high accuracy cantilever array sensor for early liver cancer diagnosis

Abstract: Early liver cancer diagnosis has clinical significance in treating cancer. Joint detection of multiple biomarkers has been considered as an effective and reliable method for early cancer diagnosis. In this work, a novel biosensor based on microcantilever array was batch-fabricated for multiple liver cancer biomarkers detection with high sensitivity, high accuracy, high throughput, and high specification. A micro-cavity was designed in the free end of the cantilever for local reaction between antibody and antigen, which can dramatically reduce the effect of adsorption-induced stiffness coefficient k variation. Furthermore,the pillar arrays in the micro-cavity were designed for increasing detection upper limit. A linear relationship between the relative frequency shift and the antigen concentration was observed for three liver cancer biomarkers, alpha-fetoprotein (AFP), γ-glutamyltranspeptidase II (GGT-2), and hepatocyte growth factor (HGF). Slight cross-reaction response to different antigens ensures high specificity of the sensor. These features will promote clinical application of the cantilever sensors in early cancer diagnosis.

Acoustic micro-vortexing of fluids, particles and cells in disposable microfluidic chips.

Abstract: We demonstrate an acoustic platform for micro-vortexing in disposable polymer microfluidic chips with small-volume (20 μl) reaction chambers. The described method is demonstrated for a variety of standard vortexing functions, including mixing of fluids, re-suspension of a pellet of magnetic beads collected by a magnet placed on the chip, and lysis of cells for DNA extraction. The device is based on a modified Langevin-type ultrasonic transducer with an exponential horn for efficient coupling into the microfluidic chip, which is actuated by a low-cost fixed-frequency electronic driver board. The transducer is optimized by numerical modelling, and different demonstrated vortexing functions are realized by actuating the transducer for varying times; from fractions of a second for fluid mixing, to half a minute for cell lysis and DNA extraction. The platform can be operated during 1 min below physiological temperatures with the help of a PC fan, a Peltier element and an aluminum heat sink acting as the chip holder. As a proof of principle for sample preparation applications, we demonstrate on-chip cell lysis and DNA extraction within 25 s. The method is of interest for automating and chip-integrating sample preparation procedures in various biological assays.

An electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells

Abstract: Olfactory ensheathing cells (OECs) are primary candidates for cell transplantation therapy to repair spinal cord injury (SCI). However, the post transplantation survival of these cells remains a major hurdle for a success using this therapy. Mechanical stimuli may contribute to the maintenance of these cells and thus, mechanotransduction studies of OECs may serve as a key benefit to identify strategies for improvement in cell transplantation. We developed an electromagnetic cell stretching device based on a single sided uniaxial stretching approach to apply tensile strain to OECs in culture. This paper reports the design, simulation and characterisation of the stretching device with preliminary experimental observations of OECs in vitro. The strain field of the deformable membrane was investigated both experimentally and numerically. Heterogeneity of the device provided an ideal platform for establishing strain requirement for the OEC culture. The cell stretching system developed may serve as a tool in exploring the mechanobiology of OECs for future SCI transplantation research.

Rapid fabrication method of a microneedle mold with controllable needle height and width.

Abstract: The main issue of transdermal drug delivery is that macromolecular drugs cannot diffuse through the stratum corneum of skin. Many studies have pursued micro-sized needles encapsulated with drugs to overcome this problem, as these needles can pierce the stratum corneum and allow drugs to enter the circulatory system of the human body. However, most microneedle fabrication processes are time-consuming and require expensive equipment. In this study, we demonstrate a rapid method for fabricating a microneedle mold using drawing lithography and a UV-cured resin. The mold was filled with a water-soluble material, polyvinylpyrrolidone (PVP), which was then demolded to produce a water-soluble microneedle array. The results of an in vitro skin insertion test using PVP microneedles and pig ear skin demonstrated the feasibility of the microneedle mold. In addition, by controlling the viscosity of the UV-cured resin through various heat treatments, microneedles with different heights and aspect ratios were produced. Compared with other methods, this technology significantly simplifies and accelerates the mold fabrication process. In addition, the required equipment is relatively simple and inexpensive. Through this technology, we can rapidly fabricate microneedle molds with controllable dimensions for various applications.

A magnetically actuated anchoring system for a wireless endoscopic capsule

Abstract: In this study, we propose a new magnetically actuated anchoring system for wireless capsule endoscopes (WCE) by employing the principle of a switchable magnetic spring A force model is derived to predict the magnetic force needed to support the interaction between the anchors and the intestinal lumen The theoretical and experimental analysis conducted shows that the magnetic spring is capable of providing the force needed to activate the anchoring mechanism, which consists of four foldable legs A prototype capsule with a size comparable with the size of a commercial WCE was designed, fabricated, and tested The in-vitro tests with a real small intestine show that the proposed anchoring mechanism is able to raise the friction force between the anchoring legs and inner wall of the intestine by more than two times after its activation using an external magnetic field Experimental results presented demonstrate that the proposed anchoring system, which has a low foot-print not taking up too much space on the capsule, can provide a reliable anchoring capability with the capsule inside the intestinal lumen

Ethosomes and organogels for cutaneous administration of crocin.

Abstract: The present study describes the production and characterization of phosphatidylcholine based ethosomes and organogels, as percutaneous delivery systems for crocin. Crocin presence did not influence ethosome morphology, while the drug slightly increased ethosome mean diameter. Importantly, the poor chemical stability of crocin has been found to be long controlled by organogel. To investigate the performance of phosphatidylcholine lipid formulations as crocin delivery system, in vivo studies, based on tape stripping and skin reflectance spectrophotometry, were performed. Tape stripping results suggested a rapid initial penetration of crocin exerted by the organogel, probably due to a strong interaction between the peculiar supramolecular aggregation structure of phospholipids in the vehicle and the lipids present in the stratum corneum and a higher maintenance of crocin concentration in the case of ethosomes, possibly because of the formation of a crocin depot in the stratum corneum. Skin reflectance spectrophotometry data indicated that both vehicles promoted the penetration of crocin through the skin, with a more rapid anti-inflammatory effect exploited by ethosomes, attributed to an ethanol pronounced penetration enhancer effect and to the carrier system as a whole.