Search Results (54)

Inertial microfluidics has gained significant attention for cell counting applications due to its simplicity, high throughput, and precision. This study utilized an inertial flow microfluidic device to count blood cell-sized microparticles, simulating normal and diseased conditions. The device could focus on and count cells sized between 7 µm and 16 µm while being observed under optical microscopes, with controlled flow rates from 1 to 15 µL/min. Suspensions of cells with ratios of 600:1 for normal conditions and 400:1 for diseased conditions were studied in microchannels at different flow rates. The methodology for counting involved using a syringe pump for precise flow actuation and employing an image-based particle counting technique through optical microscopy, utilizing the passive technique of inertial microfluidics. Results were compared using two optical microscopes across both suspension types. The key findings showed that at a 600:1 ratio of 8 µm and 15 µm cells, counts of 6.45 × 10⁷ cells/mL and 1.10 × 10⁷ cells/mL, respectively, while in the 400:1 ratio of both cells, counts of 4.5 × 10⁷ cells/mL and 2.16 × 10⁷ cells/mL, respectively, were achieved at optimal parameters. This study employed an inertial flow microfluidic device to count microparticles the size of blood cells. We assessed the counting performance using optical microscopy at two different cell ratios and validated our results against hemocytometer counts. Our findings demonstrate that the channel size 150 µm and the flow rate at 1 µL/min provided the optimal counting accuracy for both particle sizes. This device offers an efficient and adaptable solution for accurate multi-cell counting under optimized conditions and supporting applications in resource-limited medical diagnostics. Full article

Cell lysis is the starting step of many biomedical assays. Electric field-based cell lysis is widely used in many applications, including point-of-care (POC) applications, because it provides an easy one-step solution. Many electric field-based lysis methods utilize micro-electrodes to apply short electric pulses across cells. Unfortunately, these cell lysis devices produce relatively low cell lysis efficiency as electric fields do not reach a significant portion of cells in the sample. Additionally, the utility of syringe pumps for flow cells in and out of the microfluidics channel causes cell loss and low throughput cell lysis. To address these critical issues, we suspended the cells in a sessile drop and concentrated on the electrodes. We used low-frequency AC electric fields (1 Vpp, 0–100 kHz) to drive the cells effectively towards electrodes and lysed using a short pulse of 10 V. A post-lysis analysis was performed using a hemocytometer, UV-vis spectroscopy, and fluorescence imaging. The results show that the pre-electric polarization of cells, prior to applying short electrical pulses, enhances the cell lysis efficiency. Additionally, the application of AC electric fields to concentrate cells on the electrodes reduces the assay time to about 4 min. In this study, we demonstrated that low-frequency AC electric fields can be used to pre-polarize and concentrate cells near micro-electrodes and improve cell lysis efficiency. Due to the simplicity and rapid cell lysis, this method may be suitable for POC assay development. Full article

The use of plastic products or components in medical equipment and supplies results in challenges in terms of environmental sustainability and waste management for disposable, non-recyclable, and non-biodegradable materials. Medical plastic waste includes items ranging from syringes, tubing, intravenous (IV) bags, packaging, and more. Developing biodegradable replacements to petroleum-based plastics in medical equipment has not yet become an urgent priority, but it is an important endeavor. Examining alternatives involves several key themes, including material selection, testing, validation, and regulatory approval. To date, research includes studies on biodegradable polymers, composite materials, surface modifications, bacterial cellulose, three-dimensional (3D) printing with biodegradable materials, clinical trials and testing, collaboration with industry, regulatory considerations, sustainable packaging for medical devices, and life cycle analysis. The incorporation of bio-based and biodegradable plastics in the healthcare industry holds immense potential for reducing the environmental impact of medical plastic waste. The literature suggests that researchers and industry professionals are actively working towards finding sustainable alternatives that meet the stringent requirements of the medical industry. This paper reviews the efforts made so far to develop biodegradable and sustainable alternatives to plastic in medical equipment using a meta-analysis of resources, which include relevant papers published in English until June 2024. A total of 116 documents were found and screened by three reviewers for relevance. The literature reviewed indicated that various medical uses require plastics due to their unique properties, such as having strength and flexibility; being lightweight; and being able to prevent bacterial contamination. Among the alternatives, polycaprolactone (PCL), polylactic-co-glycolic acid (PLGA), starch-based acid, and polybutyric acid (PBS) have demonstrated favourable outcomes in terms of biocompatibility, safety, and efficacy. Additionally, a set of approaches to overcome these barriers and strategies is discussed alongside potential future solutions. This review aims to catalyze discussions and actions toward a more environmentally sustainable future in the medical industry by providing a comprehensive analysis of the current state, challenges, and prospects of this domain. Full article

In experiments considering cell handling in microchannels, cell sedimentation in the storage container is a key problem because it affects the reproducibility of the experiments. Here, a simple and low-cost cell mixing device (CMD) is presented; the device is designed to prevent the sedimentation of cells in a syringe during their injection into a microfluidic channel. The CMD is based on a slider crank device made of 3D-printed parts that, combined with a permanent magnet, actuate a stir bar placed into the syringe containing the cells. By using A549 cell lines, the device is characterized in terms of cell viability (higher than 95%) in different mixing conditions, by varying the oscillation frequency and the overall mixing time. Then, a dedicated microfluidic experiment is designed to evaluate the injection frequency of the cells within a microfluidic chip. In the presence of the CMD, a higher number of cells are injected into the microfluidic chip with respect to the static conditions (2.5 times), proving that it contrasts cell sedimentation and allows accurate cell handling. For these reasons, the CMD can be useful in microfluidic experiments involving single-cell analysis. Full article

We propose a nucleic acids dilution-induced assembly (NADIA) method for the preparation of lipid nanoparticles. In the conventional method, water-soluble polymers such as nucleic acids and proteins are mixed in the aqueous phase. In contrast, the NADIA method, in which self-assembly is triggered upon dilution, requires dispersion in an alcohol phase without precipitation. We then investigated several alcohols and discovered that propylene glycol combined with sodium chloride enabled the dispersion of plasmid DNA and protamine sulfate in the alcohol phase. The streamlined characteristics of the NADIA method enable the preparation of extracellular vesicles-mimicking lipid nanoparticles (ELNPs). Among the mixing methods using a micropipette, a syringe pump, and a microfluidic device, the lattermost was the best for decreasing batch-to-batch differences in size, polydispersity index, and transfection efficiency in HepG2 cells. Although ELNPs possessed negative ζ-potentials and did not have surface antigens, their transfection efficiency was comparable to that of cationic lipoplexes. We observed that lipid raft-mediated endocytosis and macropinocytosis contributed to the transfection of ELNPs. Our strategy may overcome the hurdles linked to supply and quality owing to the low abundance and heterogeneity in cell-based extracellular vesicles production, making it a reliable and scalable method for the pharmaceutical manufacture of such complex formulations. Full article

The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of lidocaine or other functional excipients, types of syringes, and injection techniques. Finished product injectability constitutes a critical quality attribute for clinical injectors, as it strongly influences product applicability and ease of use in aesthetic medicine. While injectable product extrusion force specifications are provided by the respective device manufacturers, the qualitative informative value of such datasets is low for injectors wishing to compare product brands and technologies from an injectability standpoint. Therefore, the present study comparatively assessed 28 cross-linked HA dermal fillers (JUVÉDERM^®, Restylane^®, BELOTERO^®, TEOSYAL RHA^®, and STYLAGE^® brands) using various injectability benchmarking setups for enhanced clinical-oriented relevance. Manual product injections were performed by three specialized and experienced clinicians, whereas automatic product extrusion was performed using a Texture Analyzer instrument. The various hydrogel products were injected into ex vivo human skin and into SimSkin^® cutaneous equivalents to appropriately account for injection-related counterpressure. The injectability results revealed important variability between and within product brands, with a strong influence of the local anesthetic lidocaine, HA contents, and needle gauge size. Critical appraisals of the investigated products were performed, notably from manufacturing process-based and clinical ease of application-based standpoints, centered on respective experimental injectability quality levels. Generally, it was confirmed that each HA-based dermal filler product requires specific expertise for optimal injection, mainly due to differing viscoelastic characteristics and injectability attributes. Overall, the present study set forth evidence-based and clinical-oriented rationale elements confirming the importance for injectors to work with injectable products with which they are experienced and comfortable to optimize clinical results. Full article

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10–50 μm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5–31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region. Full article

Vein blood sampling is a method of mass blood sampling that involves drawing blood from a vein for blood type discrimination, confirmation of various physiological indicators, disease diagnosis, etc.; it is the most commonly used blood sampling method. An important aspect of vein blood sampling is the search for the exact location of the vein for insertion of the syringe to draw blood. This is influenced by obesity as well as skin and blood vessel conditions in the patient and the experience of the clinical technologist, nurse, and resident who performs the blood sampling. Frequent practice is required to effectively perform blood sampling techniques. However, due to the many limitations of the practice room or laboratory, there is a problem of using only a limited environment and model for clinical practice. As a result, many medical educational institutions have situations in which only fragmentary clinical practices are performed, and it is difficult to practice many blood sampling skills, so they do not provide enough experience to understand the actual skill field. In this paper, we propose a virtual-reality-based vein blood sampling simulator that allows the practice of blood sampling techniques without limitation. The proposed vein blood sampling simulator can operate a 3D model related to vein blood sampling using an HMD controller and a haptic device in a virtual space for vein blood sampling practice by wearing an HMD (head-mounted display). Vein blood sampling can also be practiced through interaction with the patient 3D model. In addition, the effectiveness of a simulator developed for dental students was verified, and as a result of the verification, the potential of the proposed vein blood sampling simulator was confirmed. Full article

Microfluidic devices are frequently manufactured with polydimethylsiloxane (PDMS) due to its affordability, transparency, and simplicity. However, high-pressure flow through PDMS microfluidic channels lead to an increase in channel size due to the compliance of the material. As a result, longer response times are required to reach steady flow rates, which increases the overall time required to complete experiments when using a syringe pump. Due to its excellent optical properties and increased rigidity, Norland Optical Adhesive (NOA) has been proposed as a promising material candidate for microfluidic fabrication. This study compares the compliance and deformation properties of three different characteristic sized (width of parallel channels: 100, 40 and 20 µm) microfluidic devices made of PDMS and NOA. The comparison of the microfluidics devices is made based on the Young’s modulus, roughness, contact angle, channel width deformation, flow resistance and compliance. The experimental resistance is estimated through the measurement of the flow at a given pressure and a precision flow meter. The characteristic time of the system is extracted by fitting the two-element resistance-compliance (RC) hydraulic circuit model. The compliance of the microfluidics chips is estimated through the measurement of the characteristic time required for channels to achieve an output flow rate equivalent to that of the input flow rate using a syringe pump and a precision flow meter. The Young modulus was found to be 2 MPa for the PDMS and 1743 MPa for the NOA 63. The surface roughness was found to be higher for the NOA 63 than for the PDMS. The hydrophilicities of materials were found comparable with and without plasma treatment. The results show that NOA devices have lower compliance and deformation than PDMS devices. Full article

Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile. Full article

We demonstrate a method to effectively 3D print microfluidic devices with high-resolution features using a biocompatible resin based on avobenzone as the UV absorber. Our method relies on spectrally shaping the 3D printer source spectrum so that it is fully overlapped by avobenzone’s absorption spectrum. Complete overlap is essential to effectively limit the optical penetration depth, which is required to achieve high out-of-plane resolution. We demonstrate the high resolution in practice by 3D printing 15 $\mathsf{\mu }$m square pillars in a microfluidic chamber, where the pillars are separated by 7.7 $\mathsf{\mu }$m and are printed with 5 $\mathsf{\mu }$m layers. Furthermore, we show reliable membrane valves and pumps using the biocompatible resin. Valves are tested to 1,000,000 actuations with no observable degradation in performance. Finally, we create a concentration gradient generation (CG) component and utilize it in two device designs for cell chemotaxis studies. The first design relies on an external dual syringe pump to generate source and sink flows to supply the CG channel, while the second is a complete integrated device incorporating on-chip pumps, valves, and reservoirs. Both device types are seeded with adherent cells that are subjected to a chemoattractant CG, and both show clear evidence of chemotactic cellular migration. Moreover, the integrated device demonstrates cellular migration comparable to the external syringe pump device. This demonstration illustrates the effectiveness of our integrated chemotactic assay approach and high-resolution biocompatible resin 3D printing fabrication process. In addition, our 3D printing process has been tuned for rapid fabrication, as printing times for the two device designs are, respectively, 8 and 15 min. Full article

The employment of advanced analytical techniques and instrumentation enables the tracing of volatile organic compounds (VOCs) in vestigial concentrations (ppbv-pptv range) for several emerging applications, such as the research of disease biomarkers in exhaled air, the detection of metabolites in several biological processes, and the detection of pollutants for air quality control. In this scope, the storage of gaseous samples is crucial for preserving the integrity and stability of the collected set of analytes. This study aims to assess the suitability of three commercially available syringes as air containers (AC) that are commonly used for the collection, storage, isolation, and transportation of samples: glass syringes with glass plungers (AC1), and two plastic syringes, one with plastic plungers (AC2), and one with rubbered plungers (AC3). For this purpose, 99 air samples with different times of storage (from 10 min to 24 h) were analyzed using a Gas Chromatography—Ion Mobility Spectrometry device and the degradation of the samples was properly assessed by comparing the changes in the VOCs’ emission profiles. The quality of the method was assured by via the measurement of the blank’s spectra before each experimental run, as well as by the consecutive measurement of the three replicates for each sample. A statistical analysis of the changes in the VOCs’ emission patterns was performed using principal component analysis (PCA). The results, with a total explained variance of 93.61%, indicate that AC3 is the most suitable option for the long-term storage of air samples. Thus, AC3 containers demonstrated a higher capacity to preserve the stability and integrity of the analytes compared to AC1 and AC2. The findings of the short-term effects analysis, up to 1 h, confirm the suitability of all analyzed syringe-based containers for sample-transferring purposes in onsite analysis. Full article

Drug adherence is a significant medical issue, often responsible for sub-optimal outcomes during the treatment of chronic diseases such as rheumatoid or psoriatic arthritis. Monoclonal antibodies (which are exclusively given parenterally) have been proven to be an effective treatment in these cases. The use of auto-injectors is an effective strategy to improve drug adherence in parenteral treatments since these pen-like devices offer less discomfort and increased user-friendliness over conventional syringe-based delivery. This study aims to investigate the feasibility of including a monoclonal antibody as a solid formulation inside an auto-injector pen. Specifically, the objective was to evaluate the drug stability after a concentration (to reduce the amount of solvent and space needed) and freeze-drying procedure. A preliminary screening of excipients to improve stability was also performed. The nano-DSC results showed that mannitol improved the stability of the concentrated, freeze-dried antibody in comparison to its counterpart without it. However, a small instability of the C_H2 domain was still found for mannitol samples, which will warrant further investigation. The present results serve as a stepping stone towards advancing future drug delivery systems that will ultimately improve the patient experience and associated drug adherence. Full article

The aim of the case series was to determine the efficacy of a new medical device developed for adipose tissue restoration in the face. The medical device used the patented NAHYCO^® Hybrid Technology to deliver 45 mg of high- (1400 ± 200 kDa) and 45 mg of low- (100 ± 20 kDa) molecular-weight hyaluronan, in 2 mL. Patients and methods: Twenty-two volunteers, aged 36–60 years. Two mL of Profhilo^® Structura was injected using a 25 G cannula for each hemiface, into superficial fat compartment along the line from the preauricular area to the mandibular angle. Two injections were performed, and Profhilo Structura’s effect on restoring adipose tissue was evaluated immediately after treatment, and over a 6-month follow-up. The studied medical device revealed a pseudoplastic behavior and consistency that allowed easy extrusion from a syringe. It showed a lower viscosity compared to dermal fillers, based on crosslinked HA. Clinically, the soft tissue thickness increased immediately after injection, and the clinical improvement persisted across a 6-month follow-up. The self-reported satisfaction with the treatment showed an amelioration in the midface of all the subjects enrolled, with no adverse effects. Profhilo^® Structura demonstrated a peculiar fat compartment integration, with a regenerating effect on adipose tissue senescence. The skin thickening and compaction effects were similar to those obtained using chemically crosslinked dermal fillers, while a natural look was preserved, and the use of crosslinking agents was avoided. Full article

In this paper, we report the use of additive manufacturing methods to fabricate a high aspect ratio, low noise amplifier (LNA) for a handheld active sensor device operating at up to 1 GHz. The new form factor LNA incorporates a modification of a square-shaped commercial off-the-shelf (COTS) LNA into a 5:1 aspect ratio device without a loss in RF performance. For rapid prototyping, we employ both subtractive and additive manufacturing technologies, such as milling, extrusion-based syringe printing, and aerosol jet printing techniques to fabricate both small form factor and high aspect ratio devices. The 5:1 aspect ratio LNA demonstrated a 20% smaller form factor, a gain of 25 dB, and an NF less than 3 dB over an operating frequency range up to 1 GHz, comparable to the COTS LNA. Design, simulation, and experimental results are given to highlight the advantages of 3D printed hybrid electronic technology over the conventional PCB fabrication method for rapid prototyping of RF electronic devices. Full article