Monte Carlo simulation-guided design for size-tuned tumor spheroid formation in 3D printed microwells.

Tumor spheroid models have garnered significant attention in recent years as they can efficiently mimic in vivo models, and in addition, they offer a more controlled and reproducible environment for evaluating the efficacy of cancer drugs. In this study, we present the design and fabrication of a micromold template to form multicellular spheroids in a high-throughput and controlled-sized fashion. Briefly, polydimethylsiloxane-based micromolds at varying sizes and geometry were fabricated via soft lithography using 3D-printed molds as negative templates. The efficiency of spheroid formation was assessed using GFP-expressing human embryonic kidney 293 cells (HEK-293). After 7 days of culturing, circularity and cell viability of spheroids were >0.8 and 90%, respectively. At 1500 cells/microwell of cell seeding concentration, the spheroids were 454 ± 15 µm, 459 ± 7 µm, and 451 ± 18 µm when cultured in microwells with the diameters of 0.4, 0.6, and 0.8 µm, respectively. Moreover, the distance between each microwell and surfactant treatment before cell seeding notably impacted the uniform spheroid formation. The centrifugation was the key step to collect cells on the bottom of the microwells. Our findings were further verified using a commercial microplate. Furthermore, Monte Carlo simulation confirmed the seeding conditions where the spheroids could be formed. This study showed prominent steps in investigating spheroid formation, thereby leveraging the current know-how on the mechanism of tumor growth.

3D Breast Cancer Model on Silk Fibroin-Integrated Microfluidic Chips.

To imitate in vivo environment of cells, microfluidics offer controllable fashions at micro-scale and enable regulate flow-related parameters precisely, leveraging the current state of 3D systems to 4D level through the inclusion of flow and shear stress. In particular, integrating silk fibroin as an adhering layer with microfluidic chips enables to form more comprehensive and biocompatible network between cells since silk fibroin holds outstanding mechanical and biological properties such as easy processability, biocompatibility, controllable biodegradation, and versatile functionalization. In this chapter, we describe design and fabrication of a microfluidic chip, with silk fibroin-covered microchannels for the formation of 3D structures, such as MCF-7 (human breast cancer) cell spheroids as a model system. All the steps performed here are characterized by surface-sensitive tools and standard tissue culture methods. Overall, this strategy can be easily integrated into various high-tech application areas such as drug delivery systems, regenerative medicine, and tissue engineering in near future.

Advancing 3D printed microfluidics with computational methods for sweat analysis.

The intricate tapestry of biomarkers, including proteins, lipids, carbohydrates, vesicles, and nucleic acids within sweat, exhibits a profound correlation with the ones in the bloodstream. The facile extraction of samples from sweat glands has recently positioned sweat sampling at the forefront of non-invasive health monitoring and diagnostics. While extant platforms for sweat analysis exist, the imperative for portability, cost-effectiveness, ease of manufacture, and expeditious turnaround underscores the necessity for parameters that transcend conventional considerations. In this regard, 3D printed microfluidic devices emerge as promising systems, offering a harmonious fusion of attributes such as multifunctional integration, flexibility, biocompatibility, a controlled closed environment, and a minimal requisite analyte volume-features that leverage their prominence in the realm of sweat analysis. However, formidable challenges, including high throughput demands, chemical interactions intrinsic to the printing materials, size constraints, and durability concerns, beset the landscape of 3D printed microfluidic devices. Within this paradigm, we expound upon the foundational aspects of 3D printed microfluidic devices and proffer a distinctive perspective by delving into the computational study of printing materials utilizing density functional theory (DFT) and molecular dynamics (MD) methodologies. This multifaceted approach serves manifold purposes: (i) understanding the complexity of microfluidic systems, (ii) facilitating comprehensive analyses, (iii) saving both cost and time, (iv) improving design optimization, and (v) augmenting resolution. In a nutshell, the allure of 3D printing lies in its capacity for affordable and expeditious production, offering seamless integration of diverse components into microfluidic devices-a testament to their inherent utility in the domain of sweat analysis. The synergistic fusion of computational assessment methodologies with materials science not only optimizes analysis and production processes, but also expedites their widespread accessibility, ensuring continuous biomarker monitoring from sweat for end-users.

Factors affecting the success of CT-guided core biopsy of musculoskeletal lesions with a 13-G needle.

OBJECTIVE: To determine the value of CT-guided bone core biopsy and investigate factors that affect diagnostic yield and biopsy outcome. MATERIALS AND METHODS: The single-centre retrospective analysis included 447 patients who had CT-guided core biopsy with a 13-G needle (Bonopty®) from January 2016 to December 2021. Histological results or ≥ 6 months of clinical and radiological follow-up served as outcome references. A successful biopsy was classified as "diagnostic" when a definitive diagnosis was made and "adequate" when only the malignant or benign nature of the tumour could be determined. Biopsies were "nondiagnostic" when the nature of the lesion could not be determined. The occult lesions were defined as not seen on CT but visible on other modalities. RESULTS: In 275 (62%) females and 172 (38%) males, the overall success rate was 85% (383 biopsies), with 314 (70%) diagnostic biopsies and 69 (15%) adequate biopsies. There was no relationship between biopsy success and the localisation of the lesion, length of biopsy material, or number of biopsy attempts. The lesions' nature had a statistically significant effect on biopsy success with lytic and mixed lesions having the highest success rate. Occult lesions had the lowest success rate. CONCLUSION: CT-guided bone core biopsy is an effective method in the workup of musculoskeletal diseases with the highest success rate in lytic and mixed lesions. No apparent relationship was found between biopsy success and biopsy length, number of attempts, or localisation of the lesion.

In situ synthesis and dynamic simulation of molecularly imprinted polymeric nanoparticles on a micro-reactor system.

Current practices in synthesizing molecularly imprinted polymers face challenges-lengthy process, low-productivity, the need for expensive and sophisticated equipment, and they cannot be controlled in situ synthesis. Herein, we present a micro-reactor for in situ and continuously synthesizing trillions of molecularly imprinted polymeric nanoparticles that contain molecular fingerprints of bovine serum albumin in a short period of time (5-30 min). Initially, we performed COMSOL simulation to analyze mixing efficiency with altering flow rates, and experimentally validated the platform for synthesizing nanoparticles with sizes ranging from 52-106 nm. Molecular interactions between monomers and protein were also examined by molecular docking and dynamics simulations. Afterwards, we benchmarked the micro-reactor parameters through dispersity and concentration of molecularly imprinted polymers using principal component analysis. Sensing assets of molecularly imprinted polymers were examined on a metamaterial sensor, resulting in 81% of precision with high selectivity (4.5 times), and three cycles of consecutive use. Overall, our micro-reactor stood out for its high productivity (48-288 times improvement in assay-time and 2 times improvement in reagent volume), enabling to produce 1.4-1.5 times more MIPs at one-single step, and continuous production compared to conventional strategy.

Systematic triage and treatment of earthquake victims: Our experience in a tertiary hospital after the 2023 Kahramanmaras earthquake.

OBJECTIVES: The aim of this study was to evaluate the benefits of our triage system in acceleration of intervention for the musculoskeletal injuries and clinical follow-ups of trauma patients admitted to our center after the Kahramanmaras earthquake. PATIENTS AND METHODS: Between February 6th, 2023 and February 20th, 2023, a total of 439 patients (207 males, 232 females; mean age: 37.1±19.1 years; range, 1 to 94 years) with earthquake-related musculoskeletal injuries after the Kahramanmaras earthquake were retrospectively analyzed. Data including age, sex, referral city information, removal time from the rubbles, physical examination findings, clinical photos, fasciotomy and amputation stumps and levels, and X-ray images and computed tomography images of all patients were shared and archived in the WhatsApp (Meta Platforms, Inc.® ATTN/CA, USA) group called 'Earthquake' created by orthopedic surgeons. To complete the patient interventions as soon as possible and to ensure order, the patients were distributed with the teams in order through this group by the consultant orthopedic surgeon. The treatments were applied and recorded according to the skin and soft tissue conditions, and fractures of the patients. All treatments were carried out with a multi-disciplinary approach. RESULTS: Of the patients, 16.2% were children. Lower limb injuries constituted 59.07% of musculoskeletal injuries. Upper limb, pelvic, and spinal cord injuries were observed in 21.9%, 12.7%, and 6.25%, respectively. Conservative treatment was applied to 183 (41.68%) patients. The most common surgical intervention was debridement (n=136, 53.1%). External fixation was applied in the first stage to 21 (8.2%) patients with open fractures. The mean removal time from the rubbles was 32.1±29.38 h. A total of 118 limb fasciotomy operations were applied to the patients. Fifty limb amputations were performed in 40 patients at the last follow-up due to vascular insufficiency and infection. CONCLUSION: Based on our study results, we believe that a triage system using a good communication and organization strategy is beneficial to prevent treatment delay and possible adverse events in future disasters.

Aptamer-Based Point-of-Care Devices: Emerging Technologies and Integration of Computational Methods.

Recent innovations in point-of-care (POC) diagnostic technologies have paved a critical road for the improved application of biomedicine through the deployment of accurate and affordable programs into resource-scarce settings. The utilization of antibodies as a bio-recognition element in POC devices is currently limited due to obstacles associated with cost and production, impeding its widespread adoption. One promising alternative, on the other hand, is aptamer integration, i.e., short sequences of single-stranded DNA and RNA structures. The advantageous properties of these molecules are as follows: small molecular size, amenability to chemical modification, low- or nonimmunogenic characteristics, and their reproducibility within a short generation time. The utilization of these aforementioned features is critical in developing sensitive and portable POC systems. Furthermore, the deficiencies related to past experimental efforts to improve biosensor schematics, including the design of biorecognition elements, can be tackled with the integration of computational tools. These complementary tools enable the prediction of the reliability and functionality of the molecular structure of aptamers. In this review, we have overviewed the usage of aptamers in the development of novel and portable POC devices, in addition to highlighting the insights that simulations and other computational methods can provide into the use of aptamer modeling for POC integration.

Microfluidics as a Ray of Hope for Microplastic Pollution.

Microplastic (MP) pollution is rising at an alarming rate, imposing overwhelming problems for the ecosystem. The impact of MPs on life and environmental cycles has already reached a point of no return; yet global awareness of this issue and regulations regarding MP exposure could change this situation in favor of human health. Detection and separation methods for different MPs need to be deployed to achieve the goal of reversing the effect of MPs. Microfluidics is a well-established technology that enables to manipulate samples in microliter volumes in an unprecedented manner. Owing to its low cost, ease of operation, and high efficiency, microfluidics holds immense potential to tackle unmet challenges in MP. In this review, conventional MP detection and separation technologies are comprehensively reviewed, along with state-of-the-art examples of microfluidic platforms. In addition, we herein denote an insight into future directions for microfluidics and how this technology would provide a more efficient solution to potentially eradicate MP pollution.

Xenon Difluoride Dry Etching for the Microfabrication of Solid Microneedles as a Potential Strategy in Transdermal Drug Delivery.

Although hypodermic needles are a "gold standard" for transdermal drug delivery (TDD), microneedle (MN)-mediated TDD denotes an unconventional approach in which drug compounds are delivered via micron-size needles. Herein, an isotropic XeF2 dry etching process is explored to fabricate silicon-based solid MNs. A photolithographic process, including mask writing, UV exposure, and dry etching with XeF2 is employed, and the MN fabrication is successfully customized by modifying the CAD designs, photolithographic process, and etching conditions. This study enables fabrication of a very dense MNs (up to 1452 MNs cm-2 ) with height varying between 80 and 300 µm. Geometrical features are also assessed using scanning electron microscopy (SEM) and 3D laser scanning microscope. Roughness of the MNs are improved from 0.71 to 0.35 µm after titanium and chromium coating. Mechanical failure test is conducted using dynamic mechanical analyzer to determine displacement and stress/strain values. The coated MNs are subjected to less displacement (≈15 µm) upon the applied force. COMSOL Multiphysics analysis indicates that MNs are safe to use in real-life applications with no fracture. This technique also enables the production of MNs with distinct shape and dimensions. The optimized process provides a wide range of solid MN types to be utilized for epidermis targeting.

A Sustainable Solution to Skin Diseases: Ecofriendly Transdermal Patches.

Skin is the largest epithelial surface of the human body, with a surface area of 2 m2 for the average adult human. Being an external organ, it is susceptible to more than 3000 potential skin diseases, including injury, inflammation, microbial and viral infections, and skin cancer. Due to its nature, it offers a large accessible site for administrating several medications against these diseases. The dermal and transdermal delivery of such medications are often ensured by utilizing dermal/transdermal patches or microneedles made of biocompatible and biodegradable materials. These tools provide controlled delivery of drugs to the site of action in a rapid and therapeutically effective manner with enhanced diffusivity and minimal side effects. Regrettably, they are usually fabricated using synthetic materials with possible harmful environmental effects. Manufacturing such tools using green synthesis routes and raw materials is hence essential for both ecological and economic sustainability. In this review, natural materials including chitosan/chitin, alginate, keratin, gelatin, cellulose, hyaluronic acid, pectin, and collagen utilized in designing ecofriendly patches will be explored. Their implementation in wound healing, skin cancer, inflammations, and infections will be discussed, and the significance of these studies will be evaluated with future perspectives.

Label-Free Identification of Exosomes using Raman Spectroscopy and Machine Learning.

Exosomes, nano-sized extracellular vesicles (EVs) secreted from cells, carry various cargo molecules reflecting their cells of origin. As EV content, structure, and size are highly heterogeneous, their classification via cargo molecules by determining their origin is challenging. Here, a method is presented combining surface-enhanced Raman spectroscopy (SERS) with machine learning algorithms to employ the classification of EVs derived from five different cell lines to reveal their cellular origins. Using an artificial neural network algorithm, it is shown that the label-free Raman spectroscopy method's prediction ratio correlates with the ratio of HT-1080 exosomes in the mixture. This machine learning-assisted SERS method enables a new direction through label-free investigation of EV preparations by differentiating cancer cell-derived exosomes from those of healthy. This approach will potentially open up new avenues of research for early detection and monitoring of various diseases, including cancer.

Isokinetic performance and function are similar after total hip arthroplasty applied with a posterior or anterolateral approach: a randomised controlled trial.

BACKGROUND: There are ongoing debates on the effects of surgical approach on outcome after total hip arthroplasty (THA). It was hypothesised that with the anterolateral approach, trauma to the abductor arm can occur and related detrimental effects can diminish the postoperative outcomes. In this first randomised controlled trial in the literature on this subject, isokinetic performance and patient-reported functional outcomes were evaluated in patients undergoing THA with a posterior approach (PA) and an anterolateral approach (ALA). METHODS: A total of 48 patients scheduled to undergo THA were randomised to ALA or PA groups. The patients were evaluated preoperatively and at 6 and 12 months postoperatively, with flexion, extension and abduction strength measurements and the Harris Hip Score (HHS). The physiatrist performing isokinetic tests and the patients were blinded to the study groups. RESULTS: Both groups were similar in respect of age, body mass index (BMI), gender and preoperative isokinetic performance and HHS. Both groups demonstrated similar isokinetic performance (p < 0.05) and there was no difference in HHS (p < 0.05) at the 6- and 12-months follow-up evaluations. CONCLUSION: Although there is concern about potential abductor muscle damaging during ALA, the results of this randomised controlled study demonstrated that ALA can produce similar isokinetic performance and functional outcome to PA at 6 and 12 months, despite the close proximity to the abductor arm. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04640740 (retrospectively registered).

Patellar resurfacing in total knee arthroplasty leads to better isokinetic performance.

BACKGROUND: For decades there have been concerns about patellar resurfacing (PR) in total knee arthroplasty (TKA) and the individual preference of the surgeon is still the main determinant of whether or not resurfacing is applied. According to preference, surgeons can be categorized in 3 main groups of those who usually, selectively, or rarely resurface. The aim of this prospective, randomized, controlled study was to compare the isokinetic performance and clinical outcome of TKAs with PR and without PR. METHODS: A total of 50 patients scheduled to undergo TKA for primary osteoarthritis of the knee were randomly assigned to either the PR or non-PR groups. There were no significant differences between the groups in respect of age, BMI, gender and preoperative Knee Society Score (KSS) and isokinetic performance. Patients were evaluated at postoperative 3, 6, and 12 months with KSS and at 6 months and 1 year with isokinetic measurements. RESULTS: The PR group had a higher mean score, especially in the functional component of KSS, but the difference was not statistically significant. Knee extension peak torque was significantly higher in the PR group at 6 months (p = 0.029) and 1 year (p = 0.004) postoperatively. There were no significant differences between the groups in respect of knee flexion peak torque values following TKA. CONCLUSIONS: The results of this study demonstrated that PR during TKA is associated with better isokinetic performance and higher knee scores. These results support routine/usually resurfacing of the patella. For surgeons who selectively resurface the patella, the advantage of better isokinetic performance may be taking into consideration in favor of resurfacing the patella where they are undecided. LEVEL OF EVIDENCE: Level I, therapeutic study.

Effect of ozone therapy on neutrophil/lymphocyte, platelet/lymphocyte ratios, and disease activity in ankylosing spondylitis: a self-controlled randomized study.

This retrospective self-controlled randomized study was carried out with the participation of 53 patients diagnosed with ankylosing spondylitis according to the modified New York criteria. The patients who did not receive medical treatment or did not change their medical treatment within the last 6 months were included in the study. There was a statistically significant decrease in the patients' neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, C-reactive protein, Visual Analog Scale, Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Disease Activity Index scores measured after ozone therapy. There was a positive correlation between neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, mean platelet volume/lymphocyte ratio, monocyte/lymphocyte ratio and C-reactive protein, Visual Analog Scale, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index before and after ozone therapy. Our study revealed that the changes in the decreasing tendency of the markers measured in complete blood count after ozone therapy were correlated with the disease activity, which can contribute to understand the effect of ozone therapy on biomarkers.

The effects of smoking cessation on the ratios of neutrophil/lymphocyte, platelet/lymphocyte, mean platelet volume/lymphocyte and monocyte/high-density lipoprotein cholesterol.

The amount of smoking, level of smoking addiction and smoking cessation have effects on blood cells, blood lipid levels, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV)/lymphocyte ratio (MPVLR) and monocyte/high- density lipoprotein (HDL) ratio (MHR). Methods In this self-controlled experimental study, we included individuals who applied to a smoking cessation clinic and quit smoking. Their sociodemographic and clinical characteristics, the amount of cigarettes consumed (pack/year), their Fagerstrom test for nicotine dependence (FTND) results, haemogram values before and 6 months after quitting smoking, NLR, PLR, MPVLR, MHR and blood lipid levels before and after the treatment were compared retrospectively. Results The mean (SD) age of the 239 individuals who participated in the study was 41.7 (10.9) years and 55.2% of them were women. Their mean FTND score was 7.06 (2.0), and most of them (47.7%) had a very high level of addiction. After the smoking cessation treatment, their neutrophil, platelet, MPV, red cell distribution width, platelet distribution width (PDW), cholesterol, triglyceride, low- density lipoprotein, NLR, PLR, MPVLR, MHR and HDL values increased (p<0.05). The amount of smoking and level of dependence were negatively correlated with HDL, and positively correlated with other parameters. Conclusion After smoking cessation, in addition to dyslipidaemia, the NLR, PLR, MPVLR and MHR values also decreased, and the difference was found to correlate with the level of addiction and the amount of smoking.

The importance of biglycan, decorin and TGF-1 levels in the diagnosis of non-small cell lung cancer.

BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39-83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p= 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p= 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p= 0.002). In the multivariate regression analysis; Decorin < 8.13 ng/mL (OR, 10.96; 95% CI: 3.440-34.958), current smoking (OR, 3.81; 95% CI: 1.320-10.998), COPD (OR, 43.6; 95% CI: 2.082-913.081), and lower BMI (OR, 1.22; 95% CI: 1.070-1.405, p= 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment.

Influence of direct radiography in decision making during orthopaedic trauma surgery: A prospective study.

Objective: To evaluate the effects of intraoperative direct radiography on the change in the patient's treatment and the reliability of fluoroscopy in orthopaedic trauma surgery operations. Methods: A total of 773 fractures were evaluated prospectively. The surgeons involved in the case were divided into three groups according to their experiences: less than 5 years, 5-10 years and over 10 years. After each case, the fracture classification, whether any interventions were made after the X-ray, and the interventions were recorded. Results: There were 312(40%) intra-articular, 200(26%) metaphyseal, 161(21%) diaphyseal, 81(10%) pelvis-acetabulum, and 19(3%) vertebrae fractures. Surgeons needed to intervene in 71(9.2%) cases after direct-radiography. There was a significant difference between the location of the fracture and the number of interventions (p < 0.001). The most frequent interventions were intra-articular distal radius, acetabulum and intra-articular calcaneus fractures, respectively. Surgeons with more than 10 years of the experience felt the need to make fewer changes, it was statistically significant compared to the other two groups (p = 0.001 for both). Conclusion: It was found that the final evaluation with x-ray images before the operation was completed in trauma surgery affected the surgeon's decision. In particular, intra-articular fractures, acetabular fractures, and vertebral fractures are recommended to evaluate fixation with direct radiography in addition to fluoroscopy images before ending the operation. Level of evidence: LEVEL III.

Is single-stage minimally invasive plate fixation safe in open distal radius fractures with metadiaphyseal involvement?: Retrospective evaluation of 54 patients.

OBJECTIVE: The aim of this study was to evaluate the safety and results of one-stage surgery in Gustilo grade 1 and 2 open distal radius fractures with metadiaphyseal involvement. METHODS: This retrospective study included 54 patients with AO-2R3 and metadiaphyseal involvement according to the AO fracture classification. All fractures were treated with a long volar plate using the minimally invasive plate osteosynthesis (MIPO) technique. The patients were divided into two groups as open fracture group (25 patients) and closed fracture group (29 patients), and the groups were compared for their union time and complications and functional and radiological results. RESULTS: There was no statistically significant difference between the groups in terms of clinical and radiographic results (P > .05 for both). The mean union time was 12.77 (range, 8-20) weeks in the open fracture group and 12.75 (range, 8-18) weeks in the closed fracture group. There was no statistically significant difference between the groups in terms of union time (P > .05). Moreover, there was no statistically significant difference between the two groups in terms of major and minor complications. All fractures healed without the need for bone and/or soft tissue grafts. CONCLUSION: As a result of this study, using with long volar plate immediately minimally invasive plate osteosynthesis might be safely used as a single-stage definitive treatment for Gustilo grade 1 and 2 open distal radius fractures with metadiaphyseal involvement. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Smart materials: rational design in biosystems via artificial intelligence.

Industry 4.0 encompasses a new industrial revolution in which advanced manufacturing systems are interconnected with information technologies. These sophisticated data-gathering technologies have led to a shift toward smarter manufacturing processes involving the use of smart materials (SMs). The properties of SMs make them highly attractive for numerous biomedical applications. The integration of artificial intelligence (AI) enables them to be effectively used in the design of novel biomedical platforms to overcome shortcomings in the current biotechnology industry. This review summarizes recent advances in AI-assisted SMs for different healthcare products. The current challenges and future perspectives of AI-supported smart biosystems are also discussed, particularly with the regard to their applications in drug design, biosensors, theranostics, and electronic skins.

Benchmarking a Microfluidic-Based Filtration for Isolating Biological Particles.

Isolating particles from complex fluids is a crucial approach in multiple fields including biomedicine. In particular, biological matrices contain a myriad of distinct particles with different sizes and structures. Extracellular vesicles (EVs), for instance, are nanosized particles carrying vital information from donor to recipient cells, and they have garnered significant impact on disease diagnostics, drug delivery, and theranostics applications. Among all the EV types, exosome particles are one of the smallest entities, sizing from 30 to 100 nm. Separating such small substances from a complex media such as tissue culture and serum is still one of the most challenging steps in this field. Membrane filtration is one of the convenient approaches for these operations; yet clogging, low-recovery, and high fouling are still major obstacles. In this study, we design a two-filter-integrated microfluidic device focusing on dead-end and cross-flow processes at the same time, thereby minimizing any interfering factors on the recovery. The design of this platform is also numerically assessed to understand pressure-drop and flow rate effects over the procedure. As a model, we isolate exosome particles from human embryonic kidney cells cultured in different conditions, which also mimic complex fluids such as serum. Moreover, by altering the flow direction, we refresh the membranes for minimizing clogging issues and benchmark the platform performance for multitime use. By comprehensively analyzing the design and operation parameters of this platform, we address the aforementioned existing barriers in the recovery, clogging, and fouling factors, thereby achieving the use of a microfluidic device multiple times for bio-nanoparticle isolation without any notable issues.