Search Results (112)

Zirconium-89 (⁸⁹Zr) is a widely used radionuclide in immune-PET imaging due to its physical decay characteristics. Despite its importance, the production of ⁸⁹Zr radiopharmaceuticals remains largely manual, with limited cost-effective automation solutions available. To address this, we developed an automated system for the agile and reliable production of radiopharmaceuticals. The system performs transmutations, dissolution, and separation for a range of radioisotopes. Steps in the production of ⁸⁹Zr-oxalate are used as an exemplar to illustrate its use. Three-dimensional (3D) printing was exploited to design and manufacture a target holder able to include solid targets, in this case an ⁸⁹Y foil. Spot welding was used to attach ⁸⁹Y to a refractory tantalum (Ta) substrate. A commercially available CPU chiller was repurposed to efficiently cool the metal target. Furthermore, a commercial resin (ZR Resin) and compact peristaltic pumps were employed in a compact (10 × 10 × 10 cm³) chemical separation unit that operates automatically via computer-controlled software. Additionally, a standalone 3D-printed unit was designed with three automated functionalities: photolabelling, vortex mixing, and controlled heating. All components of the assembly, except for the target holder, are housed inside a commercially available hot cell, ensuring safe and efficient operation in a controlled environment. This paper details the design, construction, and modelling of the entire assembly, emphasising its innovative integration and operational efficiency for widespread radiopharmaceutical automation. Full article

Microfluidic devices rely on precise fluid control to enable complex operations in diagnostics, chemical synthesis, and biological research. Central to this control are microvalves, which regulate on-chip flow but require flexible membranes for active operation. While the laser cutting of thermoplastics offers a fast, automated method for fabricating rigid microfluidic components, integrating flexible elements like valves and pumps remains a key challenge. Thermoplastic polyurethane (TPU) membranes have been adopted to address this need but are costly and difficult to procure reliably. In this study, we present commercial food-wrap film (FWF) as a low-cost, widely available alternative membrane material. We demonstrate FWF’s compatibility with laser-cut thermoplastic microfluidic devices by successfully fabricating Quake-style valves and peristaltic pumps. FWF valves maintained reliable sealing at 40 psi, maintained stable flow rates of ~1.33 μL/min during peristaltic operation, and sustained over one million continuous actuation cycles without performance degradation. Burst pressure testing confirmed robustness up to 60 psi. Additionally, FWF’s thermal resistance up to 140 °C enabled effective thermal bonding with PMMA layers, simplifying device assembly. These results establish FWF as a viable substitute for TPU membranes, offering an accessible and scalable solution for microfluidic device fabrication, particularly in resource-limited settings where TPU availability is constrained. Full article

Microfluidic devices are tiny tools used to manipulate small volumes of liquids in various fields. However, these devices frequently require additional equipment to control fluid flow, increasing the cost and complexity of the systems and limiting their potential for widespread use in low-resource biomedical applications. Here, we present a cost-effective and simple fabrication method for PMMA microfluidic chips using laser cutting technology, along with a low-cost and open-source peristaltic pump constructed with common hardware. The pump, programmed with an Arduino microcontroller, offers precise flow control in microfluidic devices for small volume applications. The developed application for controlling the peristaltic pump is user-friendly and open source. The microfluidic chip and pump system was tested using Jurkat cells. The cells were cultured for 24 h in conventional cell culture and a microfluidic chip. The LDH assay indicated higher cell viability in the microfluidic chip (111.99 ± 7.79%) compared to conventional culture (100 ± 15.80%). Apoptosis assay indicated 76.1% live cells, 18.7% early apoptosis in microfluidic culture and 99.2% live cells, with 0.5% early apoptosis in conventional culture. The findings from the LDH and apoptosis analyses demonstrated an increase in both cell proliferation and cellular stress in the microfluidic system. Despite the increased stress, the majority of cells maintained membrane integrity and continued to proliferate. In conclusion, the chip fabrication method and the pump offer advantages, including design flexibility and precise flow rate control. This study promises solutions that can be tailored to specific needs for biomedical applications. Full article

Peristaltic pumps represent a fundamental component of hemodialysis machines. They facilitate the transfer of fluids, particularly in the collection and treatment of blood. This study aims to improve pump precision and reliability by reducing steady-state error and optimizing flow consistency, measured in milliliters per minute. A detailed characterization established the relationship between revolutions per minute (RPM) and flow rate (mL/min), with redundant mass and volume measurements supporting accuracy. To model the system’s behavior, two non-linear functions and one linear function were compared, with the polynomial model proving the most accurate and revealing the pump’s inherently non-linear flow behavior. A proportional–integral (PI) controller was then applied, and optimized through step input and non-linear least squares fitting. A key aspect of this study is a comparative validation against a commercial hemodialysis machine, configured identically with the same blood circuit diameter, tubing brand, and filter, in order to ensure equivalency in conditions. Results showed a maximum flow rate error of 0.5296%, highlighting the integration of control and characterization methods that enhance system precision, dependability, and reproducibility—critical factors for ensuring the safety and effectiveness of hemodialysis treatments. Full article

Continuous perfusion is necessary to sustain microphysiological systems and other microfluidic cell cultures. However, most of the established microfluidic perfusion systems, such as syringe pumps, peristaltic pumps, and rocker plates, have several operational challenges and may be cost-prohibitive, especially for laboratories with no microsystems engineering expertise. Here, we address the need for a cost-efficient, easy-to-implement, and reliable microfluidic perfusion system. Our solution is a modular pumpless perfusion assembly (PPA), which is constructed from commercially available, interchangeable, and aseptically packaged syringes and syringe filters. The total cost for the components of each assembled PPA is USD 1–2. The PPA retains the simplicity of gravity-based pumpless flow systems but incorporates high resistance filters that enable slow and sustained flow for extended periods of time (hours to days). The perfusion characteristics of the PPA were determined by theoretical calculations of the total hydraulic resistance of the assembly and experimental characterization of specific filter resistances. We demonstrated that the PPA enabled reliable long-term culture of engineered endothelialized 3-D microvessels for several weeks. Taken together, our novel PPA solution is simply constructed from extremely low-cost and commercially available laboratory supplies and facilitates robust cell culture and compatibility with current microfluidic setups. Full article

In recent years, microphysiological systems (MPS) using microfluidic technology as a new in vitro experimental system have shown promise as an alternative to animal experiments in the development of drugs, especially in the field of drug discovery, and some reports have indicated that MPS experiments have the potential to be a valuable tool to obtain outcomes comparable to those of animal experiments. We have commercialized the Fluid3D-X^®, a double-layer microfluidic chip made of polyethylene terephthalate (PET), under the Japan Agency for Medical Research and Development (AMED) MPS development research project and have applied it to various organ models. When intestinal epithelial cells, Caco-2, were cultured using Fluid3D-X^® and a peristaltic pump, villi-like structures were formed in the microchannels. Still, the degree of formation differed between the upstream and downstream sides. To examine the consideration points regarding the effects of the nutrient and oxygen supply by the chip material and the medium perfusion rate and direction on cells in the widely used double-layer microfluidic chip and to demonstrate the usefulness of a new imaging evaluation method using artificial intelligence technology as an assistive tool for the morphological evaluation of cells, the cell morphology in the channels was quantified and evaluated using the Nikon NIS.ai and microscopic observation. Villi-like structures were predominant upstream of the top channel, independent of the medium perfusion on the bottom channel, and those structures downstream developed with an increased flow rate. Additionally, compared to the Fluid3D-X^®, the chip made of PDMS showed almost uniform villi-like sterilization in the channel. The result indicates that the environment within the microchannels differs because the amount of nutrients and oxygen supply varies depending on the medium’s perfusion and the material of the chips. As the amount of oxygen and nutrients required by different cell types differs, it is necessary to study the optimization of culture conditions according to the characteristics of the cells handled. It was also demonstrated that the AI-based image analysis method is helpful as a quantification method for the differences in cell morphology in the microchannel observed under a microscope. Full article

Background: Vascular calcification (VC) is a dynamic, tightly regulated process driven by cellular activity and resembling the mechanisms of bone formation, with specific molecules playing pivotal roles in its progression. We aimed to investigate the involvement of the bone morphogenic proteins (BMP-2, BMP-4, BMPR-1a/1b, and BMPR-2) system in this process. Our study used an advanced in vitro model that simulates the biological environment of the vascular wall, assessing the ability of a phosphate mixture to induce the osteoblastic switch in human coronary artery smooth muscle cells (HCASMCs). Methods: HCASMCs were grown in mono- and co-culture with human coronary artery endothelial cells (HCAECs) in a double-flow bioreactor (LiveBox2 and IVTech), allowing static and dynamic conditions through a peristaltic pump. The VC was stimulated by incubation in a calcifying medium for 7 days. A BMP system Real-Time PCR was performed at the end of each experiment. Results: In monocultures, BMP-2 expression increased in calcified HCASMCs in static (p = 0.01) and dynamic conditions. BMP-4 and the biological receptors were expressed in all the experimental settings, increasing mainly in dynamic flow conditions. In co-cultures, we observed a marked increase in BMP-2 and BMP-4, BMPR-1a (p = 0.04 and p = 0.01, respectively), and BMPR-2 (p = 0.001) in the calcifying setting mostly in dynamic conditions. Conclusions: The increase in BMP-2/4 in co-culture suggests that these genes might promote the switch towards an osteogenic-like phenotype, data also supported by the rise of both BMPR-1a and BMPR-2. Thus, our findings provide insights into the mechanisms by which dynamic co-culture modulates the BMP system activation in an environment mimicking in vivo VC’s cellular and mechanical characteristics. Full article

Redox flow batteries (RFBs), with distinct characteristics that are suited for grid-scale applications, stand at the forefront of potential energy solutions. However, progress in RFB technology is often impeded by their prohibitive cost and the limited availability of essential research and development test cells. Addressing this bottleneck, we present herein an open-source device tailored for RFB laboratory research. Our proposed device significantly lowers the financial barriers to research and enhances the accessibility of vital equipment for RFB studies. Employing innovative fabrication methods such as laser cutting, 3D printing, and CNC machining, a versatile and efficient flow cell has been designed and fabricated. Furthermore, our open laboratory research equipment comprises the Opensens potentiostat, charge/discharge testing devices, peristaltic pumps, and inexpensive rotating electrodes. Every individual element contributes significantly to the establishment of an all-encompassing experimental configuration that is both economical and efficient, thereby facilitating expedited progress in RFB research and development. Full article

Background: The generation and perfusion of complex vascularized tissues in vitro requires sophisticated perfusion techniques. For multiscale arteriovenous networks, not only the arterial, but also the venous, biomechanical and biochemical conditions that physiologically exist in the human body must be accurately emulated. For this, we here present a modular arteriovenous perfusion system for the in vitro culture of a multi-scale bioartificial vascular network. Methods: The custom-built perfusion system consisted of two circuits: in the arterial circuit, physiological arterial biomechanical and biochemical conditions were simulated using a modular set-up with a pulsatile peristaltic pump, compliance chambers, and resistors. In the venous circuit, venous conditions were emulated accordingly. In the center of the system, a bioartificial multi-scale vascularized fibrin-based tissue was perfused by both circuits simultaneously under biomimetic arteriovenous conditions. Culture conditions were monitored continuously using a multi-sensor monitoring system. Results: The physiological arterial and venous pressure- and flow-curves, as well as the microvascular arteriovenous oxygen partial pressure gradient, were accurately emulated in the perfusion system. The multi-sensor monitoring system facilitated live monitoring of the respective parameters and data-logging. In a proof-of-concept experiment, vascularized three-dimensional fibrin tissues showed sustained cell viability and homogenous microvessel formation after culture in the perfusion system. Conclusions: The arteriovenous perfusion system facilitated the in vitro culture of a multiscale vascularized tissue under physiological pressure-, flow-, and oxygen-gradient conditions. With that, it presents a promising technique for the in vitro generation and culture of complex large-scale vascularized tissues. Full article

A comprehensive analysis of in vitro pumps used in cardiovascular research is provided in this review, with a focus on the characteristics of generated flows and principles of flow generations. The cardiovascular system, vital for nutrient circulation and waste removal, generates complex hemodynamics critical for endothelial cell function. Cardiovascular diseases (CVDs) could be caused by the disturbances in these flows, including aneurysms, atherosclerosis, and heart defects. In vitro systems simulate hemodynamic conditions on cultured cells in the laboratory to study and evaluate these diseases to advance therapies. Pumps used in these systems can be classified into contact and non-contact types. Contact pumps, such as piston and gear pumps, can generate higher flow rates, but they have a higher risk of contamination due to the direct interaction of pump with the fluid. Non-contact pumps, such as peristaltic and lab-on-disk centrifugal pumps, minimize contamination risks, but they are limited to lower flow rates. Advanced pumps including piezoelectric and I-Cor diagonal pumps are focused on improving the accuracy of flow replication and long-term stability. The operational principles, advantages, and some disadvantages of these pump categories are evaluated in this review, while providing insights for optimizing in vitro cardiovascular models and advancing therapeutic strategies against CVDs. The outcomes of the review elaborate the importance of selecting an appropriate pump system, to accurately replicate cardiovascular flow patterns. Full article

Background: Infusion pumps are critical in delivering fluids, including medications and blood products, in controlled amounts. However, conventional pumps can cause hemolysis and other issues such as flow variations and infection risks, especially during blood transfusions. To address these limitations, a novel cylinder-type infusion pump, the Anyfusion H-100, was developed, which includes a specialized blood transfusion cartridge set that combines syringe and peristaltic infusion methods. This study evaluates the accuracy and hemolysis rates of the Anyfusion H-100 compared to conventional pumps, aiming to confirm its viability as a safe and effective medical device for blood transfusions. Methods: This study evaluated six different infusion rates (10–180 cc/hr) and conducted 57 transfusion trials, 20 of which used a 1:1 blood–saline dilution. Blood transfusion accuracy was measured using research-grade packed red blood cells, and hemolysis rates were assessed before and after transfusion by chi-square tests and independent sample t-tests. Results: Anyfusion demonstrated an average transfusion error rate of 3.77%, compared to 4.00% for the Terufusion, with no statistically significant difference in hemolysis rates (p = 0.697). Bland–Altman plots confirmed their equivalent performance, with hemolysis rates of 0.566 ± 0.095% for Anyfusion and 0.518 ± 0.126% for Terufusion. Conclusions: Anyfusion provides an accurate and reliable blood transfusion performance comparable to that of Terufusion, with no significant difference in hemolysis rates; its integration of syringe and infusion methods shows a potential for safer and more efficient transfusion practices, especially in pediatric and emergency settings. Full article

This study investigates the fabrication of 3D-printed microfluidic devices for solid/liquid separation, focusing on additive manufacturing technologies. Stereolithography (SLA) and fused filament fabrication (FFF) were used to create microseparators with intricate designs optimized for separation efficiency. Model suspensions containing quartz sand, nano-calcium carbonate, and talc-based baby powder in water were prepared using an electric magnetic stirrer and conveyed into the microseparator via a peristaltic pump. Different flow rates were tested to evaluate their influence on the separation efficiency. The highest separation efficiency for the model systems was observed at a flow rate of 200 mL min⁻¹. This was due to the increased turbulence at higher flow rates, which hindered the secondary flow perpendicular to the primary flow direction. The particle size distribution before and after separation was analyzed using sieve and laser diffraction, and particle morphology was inspected by scanning electron microscopy. The laser diffraction analysis revealed post-separation particle size distributions, indicating that Outlet 1 (external stream) consistently captured larger particles more effectively than Outlet 2 (internal stream). This work highlights the potential of additive manufacturing to produce customized microfluidic devices, enabling rapid prototyping and fine-tuning of complex geometries, thus enhancing separation efficiency across various industrial applications. Full article

Technological advancements are propelling medical technology towards automation through the application and widespread use of automatic control, sensing, and Internet of Things (IoT) technologies. Currently, IoT technology has been extensively applied in medical devices, aiming to ensure patient safety through more real-time detection and more effective management. In the monitoring of intravenous infusion, accurately sensing the infusion conditions in real time is particularly important. This article introduces a low-cost smart infusion device based on IoT technology, which controls the infusion rate with a peristaltic pump and monitors the volume of fluid delivered. It uses an improved, self-calibrating weighing sensor to achieve the real-time closed-loop control of the flow rate, ensuring patient safety. Additionally, the Blynk dashboard can be used for monitoring and controlling the flow rate and infusion volume. Full article

Peristaltic flow in a straight rectangular duct is examined imposed by contraction pulses implemented by pairs of horizontal cylindrical segments with their axes perpendicular to the flow direction. The wave propagation speed is considered in such a range that triggers a laminar fluid motion. The setting is analyzed over a set of variables which includes the propagation speed, the relative occlusion, the modality of the squeezing pulse profile and the Carreau power index. The numerical solution of the equations of motion on Cartesian meshes is grounded in the immersed boundary method. An increase in the peristaltic pulse modality leads to the reduction in the shear rate levels on the central tube axis and to the movement of the peristaltic characteristics to higher pressure values. The effect of the no slip side walls (NSSWs) is elucidated by the collation with relevant results for the flow field produced under the same assumptions though with slip side walls (SSWs). Shear thinning behavior exhibits a significantly larger effect on transport efficiency for the NSSWs duct than on the SSWs duct. Full article

In situ evaluations of the metabolic rates (i.e., respiration and excretion) of salmonid eggs are mostly indirect, focusing on the sampling of hyporheic water from wild or artificial nests. Comparatively, experimental studies carried out under controlled, laboratory conditions are less abundant due to methodological difficulties. This study presents a novel experimental setup aimed to address this issue and enable the measurement of oxygen and dissolved inorganic nitrogen fluxes in simulated rainbow trout (O. mykiss) egg pockets. The experimental setup consists of reconstructed egg pockets in cylindrical cores under flow-through conditions. Live and dead eyed-stage eggs were incubated in a natural, sterilised gravel substrate. Hyporheic water circulation was ensured using peristaltic pumps, with the possibility to collect and analyse inflowing and outflowing water for chemical analyses. Microcosm incubations, with closed respirometry of eggs in water alone, were also carried out in order to infer the importance of microbial respiration in the simulated egg pockets. The results show an increasing trend in oxygen demand, due to the development of biofilm in the reconstructed egg pockets and increased egg respiration rates. Moreover, egg pockets showed positive ammonium net fluxes connected with the advancing developmental egg stage, while nitrate removal peaked during the last phase of the experiment, mainly due to the formation of oxic-hypoxic interfaces, leading to couple nitrification–denitrification processes. The suggested approach enables to test a number of in situ situations, including the effects of extreme hydrological conditions, sediment clogging and sudden changes in water chemistry or temperature on the survival and metabolic performances of nests, at different egg development stages. Full article