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Stereolithography (SLA) and other photopolymerization-based additive manufacturing approaches are becoming popular for the fabrication of microfluidic devices and cell-infused platforms, but many of the resins employed in these techniques are cytotoxic to cells or do not have the appropriate mechanical properties for microfluidic components. Here, using a commercially available resin, we demonstrate that biocompatibility and a range of mechanical properties can be achieved through post-print optimization involving baking, soaking, network swelling, and UV exposure. We show that UV-vis spectrophotometry can be used to detect methacrylate monomer/oligomer, and utilizing this method, we found that baking at 120 °C for 24 hours was the optimal method for removing cytotoxic chemical species and creating nontoxic cell culture platforms, though UV exposure and soaking in 100% ethanol also can substantially reduce cytotoxicity. Furthermore, we show that the mechanical properties can be modified, including up to 50% for the Young's modulus and an order of magnitude for the flexural modulus, through the post-processing approach employed. Based on the study results, users can choose post-processing approaches to achieve needed cytotoxicity and mechanical profiles, simultaneously.
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Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.
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Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Nervio Ciático , Tacrolimus , Animales , Tacrolimus/farmacología , Tacrolimus/administración & dosificación , Regeneración Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/terapia , Ratas , Nervio Ciático/lesiones , Nervio Ciático/efectos de los fármacos , Ratas Sprague-Dawley , Poliésteres/química , Modelos Animales de Enfermedad , Regeneración Tisular Dirigida/métodosRESUMEN
Tuberculosis (TB) represents a major public health threat, with millions of new cases reported worldwide each year. A major hurdle to curtailing the spread of this disease is the need for low-cost, point-of-care (PoC) diagnostics. Mannose-capped lipoarabinomannan, a significant component of the Mycobacterium tuberculosis bacillus, has been heavily studied as a biomarker for TB, but with little success due to its complexation with endogenous components of body fluids in a manner that sterically interferes with its detection by ELISA and other immunoassays. Recent work by our group and others has shown that complexation can be disrupted with protein-denaturing protocols. By way of followup, we recently described an enzymatic digestion (Proteinase K) sample pretreatment that enables quantitative recovery of ManLAM spiked into healthy human control serum. Herein, we report on the transfer of our benchtop sample pretreatment methodology to an automated microfluidic platform. We show that this platform can be configured to: (1) carry out the pretreatment process with very little user interaction and, (2) yield recoveries for ManLAm spiked into control serum which are statistically indistinguishable from those achieved by the benchtop process. Plans to integrate this device with a portable sample reader as a possible basis for a PoC TB diagnostic system and analyze patient samples are briefly discussed.
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Biomarcadores , Lipopolisacáridos , Manosa , Tuberculosis , Humanos , Lipopolisacáridos/sangre , Biomarcadores/sangre , Tuberculosis/sangre , Tuberculosis/diagnóstico , Manosa/química , Manosa/sangre , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodosRESUMEN
OBJECTIVE: Hand-sutured (HS) techniques remain the gold standard for most microvascular anastomoses in microsurgery. HS techniques can result in endothelial lacerations and back wall suturing, leading to complications such as thrombosis and free tissue loss. A novel force-interference-fit vascular coupling device (FIF-VCD) system can potentially reduce the need for HS and improve end-to-end anastomosis. This study aims to describe the development and testing of a novel FIF-VCD system for 1.5 to 4.0 mm outside diameter arteries and veins. METHODS: Benchtop anastomoses were performed using porcine cadaver arteries and veins. Decoupling force and anastomotic leakage were tested under simulated worst-case intravital physiological conditions. The 1.5 mm FIF-VCD system was used to perform cadaver rat abdominal aorta anastomoses. RESULTS: Benchtop testing showed that the vessels coupled with the FIF-VCD system could withstand simulated worst-case intravital physiological conditions with a 95% confidence interval for the average decoupling force safety factor of 8.2 ± 1.0 (5.2 ± 1.0 N) and a 95% confidence interval for the average leakage rate safety factor of 26 ± 3.6 (8.4 ± 0.14 and 95 ± 1.4 µL/s at 150 and 360 mmHg, respectively) when compared to HS anastomotic leakage rates (310 ± 14 and 2,100 ± 72 µL/s at 150 and 360 mmHg, respectively). The FIF-VCD system was successful in performing cadaver rat abdominal aorta anastomoses. CONCLUSION: The FIF-VCD system can potentially replace HS in microsurgery, allowing the safe and effective connection of arteries and veins. Further studies are needed to confirm the clinical viability and effectiveness of the FIF-VCD system.
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Fuga Anastomótica , Venas , Ratas , Animales , Fuga Anastomótica/cirugía , Venas/cirugía , Arterias , Anastomosis Quirúrgica , Microcirugia , CadáverRESUMEN
Shiga toxins (1, 2) regularly cause outbreaks and food recalls and pose a significant health risk to the infected population. Therefore, new reliable tools are needed to rapidly detect Shiga toxin cost-effectively in food, water, and wastewater before human consumption. Enzyme immunoassay and polymerase chain reaction approaches are the gold standard detection methods for the Shiga toxin. However, these methods require expensive instruments along with expensive reagents, which makes them hard to convert into point-of-use and low-cost systems. This study introduces an electrochemical biosensing method that utilizes silver nanoparticles (AgNPs) as electrochemical tags and commercially available low-cost screen-printed carbon electrodes for detection. This study introduces the modification of reference electrodes on commercially available screen-printed carbon electrodes to detect AgNPs dissolved in nitric acid. This biosensor achieved a 2 ng/mL lowest measured concentration for Shiga toxin-1 in less than 3 h. These biosensor results also showed that the AgNP-based sensor has better linearity (for graph between peak current vs concentration) and lower standard deviation compared to gold nanoparticles (AuNP)-based electrochemical biosensors.
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Electroporation is regularly used to deliver agents into cells, including transgenic materials, but it is not used for mutating zebrafish embryos due to the lack of suitable systems, information on appropriate operating parameters, and the challenges posed by the protective chorion. Here, a novel method for gene delivery in zebrafish embryos was developed by combining microinjection into the space between the chorion and the embryo followed by electroporation. This method eliminates the need for chorion removal and injecting into the space between the chorion and embryo eliminates the need for finding and identifying key cell locations before performing an injection, making the process much simpler and more automatable. We also developed a microfluidic electroporation system and optimized electric pulse parameters for transgenesis of embryos. The study provided a novel method for gene delivery in zebrafish embryos that can be potentially implemented in a high throughput transgenesis or mutagenesis system.
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ChatGPT is a generative AI model that has garnered tremendous public interest due to its ability to solve diverse problems through high-level reasoning and analysis. Among its features is an ability to create and debug code. While this capability has been explored with conventional programming languages such as Python, it has yet to be applied to computer-aided design (CAD). In this work, we utilized GPT-4 to create functional microfluidic components using OpenSCAD, an open-source CAD software package. Through an iterative dialogue, GPT-4 created functional designs for a helix/spiral, a valve, a t-junction, and a serpentine channel. This concept could facilitate CAD in the future for both technical and non-technical users and can be reasonably extended to other fields.
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The objective of this study was to determine if locally delivered FK506 could prevent allogeneic nerve graft rejection long enough to allow axon regeneration to pass through the nerve graft. An 8mm mouse sciatic nerve gap injury repaired with a nerve allograft was used to assess the effectiveness of local FK506 immunosuppressive therapy. FK506-loaded poly(lactide-co-caprolactone) nerve conduits were used to provide sustained local FK506 delivery to nerve allografts. Continuous and temporary systemic FK506 therapy to nerve allografts, and autograft repair were used as control groups. Serial assessment of inflammatory cell and CD4+ cell infiltration into the nerve graft tissue was performed to characterize the immune response over time. Nerve regeneration and functional recovery was serially assessed by nerve histomorphometry, gastrocnemius muscle mass recovery, and the ladder rung skilled locomotion assay. At the end of the study, week 16, all the groups had similar levels of inflammatory cell infiltration. The local FK506 and continuous systemic FK506 groups had similar levels of CD4+ cell infiltration, however, it was significantly greater than the autograft control. In terms of nerve histmorphometry, the local FK506 and continunous systemic FK506 groups had similar amounts of myelinated axons, although they were significantly lower than the autograft and temporary systemic FK506 group. The autograft had significantly greater muscle mass recovery than all the other groups. In the ladder rung assay, the autograft, local FK506, and continuous systemic FK506 had similar levels of skilled locomotion performance, whereas the temporary systemic FK506 group had significanty better performance than all the other groups. The results of this study suggest that local delivery of FK506 can provide comparable immunosuppression and nerve regeneration outcomes as systemically delivered FK506.
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Axones , Rechazo de Injerto , Regeneración Nerviosa , Tacrolimus , Animales , Ratones , Aloinjertos , Tacrolimus/farmacología , Sistemas de Liberación de Medicamentos , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & controlRESUMEN
Natural organic matter (NOM) readily interacts with nanoparticles, leading to the formation of NOM corona structures on their surface. NOM corona formation is closely related to the surface coatings and bioavailability of nanoparticles. However, the mechanism underlying NOM corona formation on silver nanoparticles (AgNPs) remains largely unknown due to the lack of effective analytical methods for identifying the changes in the AgNP surface. Herein, the separation ability of biased cyclical electrical field-flow fractionation (BCyElFFF) for same-sized polyvinyl pyrrolidone-coated and poly(ethylene glycol)-coated silver nanoparticles (AgNPs) with different electrophoretic mobilities was evaluated under various electrical conditions. Then, the mechanism behind the NOM corona formation on these AgNP surfaces was elucidated based on the changes in the elution time and off-line characterization of the collected fractions during their elution time in a BCyElFFF run. Finally, the survival rates of E. coli exposed to polyvinyl pyrrolidone-coated and poly(ethylene glycol)-coated AgNPs with or without NOM collected during repeated BCyElFFF runs were observed to increase with increasing NOM concentration, clearly demonstrating the negative effect of NOM corona structures on the bioavailability of AgNPs. These findings highlight the powerful separation and isolation ability of BCyElFFF in studying the transformation and fate of nanoparticles in aqueous environments.
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Nanopartículas del Metal , Plata , Escherichia coli , Polivinilos , Polietilenglicoles , PovidonaRESUMEN
Zebrafish have emerged as a useful model for biomedical research and have been used in environmental toxicology studies. However, the presence of the chorion during the embryo stage limits cellular exposure to toxic elements and creates the possibility of a false-negative or reduced sensitivity in fish embryo toxicity testing (FET). This paper presents the use of electroporation as a technique to improve the delivery of toxic elements inside the chorion, increasing the exposure level of the toxins at an early embryo stage (<3 h post-fertilization). A custom-made electroporation device with the required electrical circuitry has been developed to position embryos between electrodes that provide electrical pulses to expedite the entry of molecules inside the chorion. The optimized parameters facilitate material entering into the chorion without affecting the survival rate of the embryos. The effectiveness of the electroporation system is demonstrated using Trypan blue dye and gold nanoparticles (AuNPs, 20-40 nm). Our results demonstrate the feasibility of controlling the concentration of dye and nanoparticles delivered inside the chorion by optimizing the electrical parameters, including pulse width, pulse number, and amplitude. Next, we tested silver nanoparticles (AgNPs, 10 nm), a commonly used toxin that can lower mortality, affect heart rate, and cause phenotypic defects. We found that electroporation of AgNPs reduces the exposure time required for toxicity testing from 4 days to hours. Electroporation for FET can provide rapid entry of potential toxins into zebrafish embryos, reducing the time required for toxicity testing and drug delivery experiments.
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Viscoelastic flow has been widely used in microfluidic particle separation processes, in which particles get focused on the channel center in diluted viscoelastic flow. In this paper, the transition from single-stream focusing to multiple-streams focusing (MSF) in high viscoelastic flow is observed, which is applied for cell separation processes. Particle focusing stream bifurcation is caused by the balance between elastic force and viscoelastic secondary flow drag force. The influence of cell physical properties, such as cell dimension, shape, and deformability, on the formation of multiple-streams focusing is studied in detail. Particle separation is realized utilizing different separation criteria. The size-based separation of red (RBC) and white (WBC) blood cells is demonstrated in which cells get focused in different streams based on their dimension difference. Cells with different deformabilities get stretched in the viscoelastic flow, leading to the change of focusing streams, and this property is harnessed to separate red blood cells infected with the malaria parasite, Plasmodium falciparum. The achieved results promote our understanding of particle movement in the high viscoelastic flow and enable new particle manipulation and separation processes for sample treatment in biofluids.
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Proper pain management is well understood to be one of the fundamental aspects of a healthy postoperative recovery in conjunction with mobility and nutrition. Approximately, 10% of patients prescribed opioids after surgery continue to use opioids in the long-term and as little as 10 days on opioids can result in addiction. In an effort to provide physicians with an alternative pain management technique, this work evaluates the material properties of a novel local anesthetic delivery system designed for controlled release of bupivacaine for 72 hours. The formulation utilizes solid-lipid microparticles that encapsulate the hydrophobic molecule bupivacaine in its free-base form. The lipid microparticles are suspended in a non-crosslinked hyaluronic acid hydrogel, which acts as the microparticle carrier. Two different particle manufacturing techniques, milling and hot homogenization, were evaluated in this work. The hot homogenized particles had a slower and more controlled release than the milled particles. Rheological techniques revealed that the suspension remains a viscoelastic fluid when loaded with either particle type up to 25% (w/v) particles densities. Furthermore, the shear thinning properties of the suspension media, hyaluronic acid hydrogel, were conserved when bupivacaine-loaded solid-lipid microparticles were loaded up to densities of 25% (w/v) particle loading. The force during injection was measured for suspension formulations with varying hyaluronic acid hydrogel concentrations, particle densities, particle types and particle sizes. The results indicate that the formulation viscosity is highly dependent on particle density, but hyaluronic acid hydrogel is required for lowering injection forces as well as minimizing clogging events.
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Anestésicos Locales , Ácido Hialurónico , Bupivacaína/química , Preparaciones de Acción Retardada/química , Humanos , Ácido Hialurónico/química , Hidrogeles , Lípidos , Microesferas , Tamaño de la Partícula , ViscosidadRESUMEN
Nanoscale and microscale cell-derived extracellular vesicle types and subtypes are of significant interest to researchers in biology and medicine. Extracellular vesicles (EVs) have diagnostic and therapeutic potential in terms of biomarker and nanomedicine applications. To enable such applications, EVs must be isolated from biological fluids or separated from other EV types. Developing methods to fractionate EVs is of great importance to EV researchers. Our goal was to begin to develop a device that would separate medium EVs (mEVs, traditionally termed microvesicles or shedding vesicles) and small EVs (sEVs, traditionally termed exosomes) by elasto-inertial effect. We sought to develop a miniaturized technology that works similar to and provides the benefits of differential ultracentrifugation but is more suitable for EV-based microfluidic applications. The aim of this study was to determine whether we could use elasto-inertial focusing to re-isolate and recover U87 mEVs and sEVs from a mixture of mEVs and sEVs isolated initially by one round of differential ultracentrifugation. The studied spiral channel device can continuously process 5 ml of sample fluid per hour. Using the channel, sEVs and mEVs were recovered and re-isolated from a mixture of U87 glioma cell-derived mEVs and sEVs pre-isolated by one round of differential ultracentrifugation. Following two passes through the spiral channel, approximately 55% of sEVs were recovered with 6% contamination by mEVs (the recovered sEVs contained 6% of the total mEVs). In contrast, recovery of U87 mEVs and sEVs re-isolated using a typical second centrifugation wash step was only 8% and 53%, respectively. The spiral channel also performed similar to differential ultracentrifugation in reisolating sEVs while significantly improving mEV reisolation from a mixture of U87 sEVs and mEVs. Ultimately this technology can also be coupled to other microfluidic EV isolation methods in series and/or parallel to improve isolation and minimize loss of EV subtypes.
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Exosomas , Vesículas Extracelulares , Glioblastoma , Centrifugación , Medios de Cultivo , Humanos , UltracentrifugaciónRESUMEN
As one type of non-Newtonian fluid, viscoelastic fluids exhibit unique properties that contribute to particle lateral migration in confined microfluidic channels, leading to opportunities for particle manipulation and separation. In this paper, particle focusing in viscoelastic flow is studied in a wide range of polyethylene glycol (PEO) concentrations in aqueous solutions. Polystyrene beads with diameters from 3 to 20 µm are tested, and the variation of particle focusing position is explained by the coeffects of inertial flow, viscoelastic flow, and Dean flow. We showed that particle focusing position can be predicted by analyzing the force balance in the microchannel, and that particle separation resolution can be improved in viscoelastic flows.
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Herein, we describe the simulation of a novel flow-electrical-split flow thin (Fl-El-SPLITT) separation device and validate it using existing theory and experimentation for the first time using polystyrene particles of 28 and 1000 nm diameters. The fraction of particles exiting selected ports with DC El-SPLITT is predicted with existing theory, but the theory does not include AC fields, nor does it incorporate the use of crossflows. Using DC fields the El-SPLITT simulation and theory calculated transition points result in the same values. These calculated values accurately predict the experimentally obtained transition point using a 50:50 outlet splitting plane (OSP). Relative to actual experimentally obtained transition points, the calculated values lag behind for a 90:10 OSP, and lead ahead for a 10:90 OSP. The simulation explains trends seen in AC testing, and reasonably predicts the fraction of particles exiting each port. As DC current increases, the amount of AC current required to scatter the particles away from the DC-intended port decreases. The simulation also models a crossflow in a SPLITT system with a DC current applied in a direction opposite the crossflow with some success. Long term steady-state testing without crossflows shows a DC voltage dependent loss of particles. At 8 V DC, total recovery of 28 and 1000 nm particles was 70% and 26%, respectively. This work effectively models a new Fl-El-SPLITT system via Matlab simulation by demonstrating key experimental results such as the influence of DC, AC, and crossflows on the SPLITT separation of polystyrene particles.
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Cromatografía , Electricidad , Cromatografía/métodosRESUMEN
A previously reported microvascular coupler was shown to effectively create vascular anastomoses, but was too large for practical clinical use. To safely reduce coupler size, certain failure modes needed to be better understood. The coupler functions, in part, by compressing the vessel wall between two concentric rings, creating a friction fit that anchors the device to the vessel. This work investigates the relationship between vessel wall compression and resulting friction fit strength to ensure reducing coupler size will not unduly increase the risk that this friction fit might fail. Vascular walls were compressed to a specified strain and the tensile force required to overcome the resulting friction was measured. Experiments were conducted with various vessel types (Porcine common carotid artery, splenic artery, and jugular vein), across a range of compressive strains (55-95%), and by using either PEEK or HDPE to compress the vessel. Tensile force was increased at a rate of 5 g/min or held constant for 24 h. For experiments with incrementally increasing force, the force at failure varied with compressive strain via a power function. At 70% compression, PEEK produced 4.6 times stronger friction fits than HDPE, and common carotid arteries and splenic arteries produced 1.8 and 1.3 times stronger fits than jugular veins respectively. For experiments where tensile force was applied for 24 h, much lower forces were required to overcome friction. These results were compared to friction fit failure in a coupler prototype and it was found that the prototypes failed at just 30% of the force required to cause vessel slip under the other test conditions. These results were used to develop a model that predicts the probability of device failure via vessel slipping (one design, smaller than previously reported, was estimated to fail at maximum in vivo axial stress once in 500 anastomoses, a potentially safe level of risk).
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Venas Yugulares , Fenómenos Mecánicos , Anastomosis Quirúrgica , Animales , Fricción , Presión , PorcinosRESUMEN
Immotile and rare sperm isolation from a complex cell background is an essential process for infertility treatment. The traditional sperm collection process from a biopsy sample requires long, tedious searches, yet still results in low sperm retrieval. In this work, a high recovery, high throughput sperm separation process is proposed for the clinical biopsy sperm retrieval process. It is found that sperm have different focusing positions compared with non-sperm cells in the inertial flow, which is explained by a sperm alignment phenomenon. Separation in the spiral channel device results in a 95.6% sperm recovery in which 87.4% of non-sperm cells get removed. Rare sperm isolation from a clinical biopsy sample is performed with the current approach. The chance of finding sperm is shown to increase 8.2 fold in the treated samples. The achieved results highly support this method being used for the development of a rapid biopsy sperm sorting process. In addition, the mechanism was proposed and can be applied for the high-efficiency separation of non-spherical particles in general.
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Espermatozoides , Biopsia , Separación Celular , MasculinoRESUMEN
In this work, a new high-volume, continuous particle separation device that separates based upon size and charge is described. Two continuous flow-electrical-split-flow lateral transport thin (Fl-El-SPLITT) device architectures (a platinum electrode on a porous membrane and a porous graphite electrode under a membrane) were developed and shown to improve particle separations over a purely electrical-SPLITT device. The graphite FL-El-SPLITT device architecture achieved the best separation of approximately 60% of small (28 nm) vs large (1000 nm) polystyrene particles. Fl-El-SPLITT (platinum) achieved a 75% separation on a single pass using these same particles. Fl-El-SPLITT (platinum) achieved a moderate 26% continuous separation of U87 glioma cell-derived small extracellular vesicles (EVs) from medium EVs. Control parameter testing showed that El-SPLITT continuously directed particle motility within a channel to exit a selected port based upon the applied voltage using either direct current or alternating current. The transition from one port to the other was dependent upon the voltage applied. Both large and small polystyrene particles transitioned together rather than separating at each of the applied voltages. These data present the first ever validation of El-SPLITT in continuous versus batch format. The Fl-El-SPLITT device architecture, monitoring, and electrical and fluid interfacing systems are described in detail for the first time. Capabilities afforded to the system by the flow addition include enhanced particle separation as well as the ability to filter out small particles or desalinate fluids. High-throughput continuous separations based upon electrophoretic mobility will be streamlined by this new technique that combines electrical and flow fields into a single device.
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Fraccionamiento Químico , Electricidad , Tamaño de la Partícula , Fenómenos FísicosRESUMEN
The objective of this work was to develop a model and understand the diffusion of a drug into and throughout a drug delivering nerve conduit from a surrounding reservoir through a hole in the wall separating the lumen of the conduit and the reservoir. A mathematical model based on Fick's law of diffusion was developed using the finite difference method to understand the drug diffusion and the effect of varying device parameters on the concentration of drug delivered from a hole-based drug delivery device. The mathematical model was verified using a physical microfluidic (µFD) model and an in vitro/in vivo release test using prototype devices. The results of the mathematical model evaluation and microfluidic device testing offered positive insight into the reliability and function of the reservoir and hole-based drug delivering nerve conduit. The mathematical model demonstrated how changing device parameters would change the drug concentration inside the device. It was observed that the drug release in the conduit could be tuned by both concentration scaling and changing the hole size or number of holes. Based on the results obtained from the microfluidic device, the error in the mathematical drug release model was shown to be less than 10% when comparing the data obtained from mathematical model and µFD model. The data highlights the flexibility of having a hole-based drug delivery system, since the drug release can be scaled predictably by changing the device parameters or the concentration of the drug in the reservoir. Graphical abstract .
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Sistemas de Liberación de Medicamentos , Preparaciones Farmacéuticas , Difusión , Liberación de Fármacos , Reproducibilidad de los ResultadosRESUMEN
The unprecedented global pandemic known as SARS-CoV-2 has exercised to its limits nearly all aspects of modern viral diagnostics. In doing so, it has illuminated both the advantages and limitations of current technologies. Tremendous effort has been put forth to expand our capacity to diagnose this deadly virus. In this work, we put forth key observations in the functionality of current methods for SARS-CoV-2 diagnostic testing. These methods include nucleic acid amplification-, CRISPR-, sequencing-, antigen-, and antibody-based detection methods. Additionally, we include analysis of equally critical aspects of COVID-19 diagnostics, including sample collection and preparation, testing models, and commercial response. We emphasize the integrated nature of assays, wherein issues in sample collection and preparation could impact the overall performance in a clinical setting.