PSMA-targeted radiotheranostics in modern nuclear medicine: then, now, and what of the future?

In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the landscape dramatically altered. Currently, men face a one-in-nine lifetime risk of PCa, accentuated by improved diagnostic methods and an ageing population. With more than three million men in the United States alone grappling with this disease, the overall risk of succumbing to stands at one in 39. The intricate clinical and biological diversity of PCa poses serious challenges in terms of imaging, ongoing monitoring, and disease management. In the field of theranostics, diagnostic and therapeutic approaches that harmoniously merge targeted imaging with treatments are integrated. A pivotal player in this arena is radiotheranostics, employing radionuclides for both imaging and therapy, with prostate-specific membrane antigen (PSMA) at the forefront. Clinical milestones have been reached, including FDA- and/or EMA-approved PSMA-targeted radiodiagnostic agents, such as [18F]DCFPyL (PYLARIFY®, Lantheus Holdings), [18F]rhPSMA-7.3 (POSLUMA®, Blue Earth Diagnostics) and [68Ga]Ga-PSMA-11 (Locametz®, Novartis/ ILLUCCIX®, Telix Pharmaceuticals), as well as PSMA-targeted radiotherapeutic agents, such as [177Lu]Lu-PSMA-617 (Pluvicto®, Novartis). Concurrently, ligand-drug and immune therapies designed to target PSMA are being advanced through rigorous preclinical research and clinical trials. This review delves into the annals of PSMA-targeted radiotheranostics, exploring its historical evolution as a signature molecule in PCa management. We scrutinise its clinical ramifications, acknowledge its limitations, and peer into the avenues that need further exploration. In the crucible of scientific inquiry, we aim to illuminate the path toward a future where the enigma of PCa is deciphered and where its menace is met with precise and effective countermeasures. In the following sections, we discuss the intriguing terrain of PCa radiotheranostics through the lens of PSMA, with the fervent hope of advancing our understanding and enhancing clinical practice.

Synthesis and active manipulation of magnetic liquid beads.

We report the fabrication and characterisation of magnetic liquid beads with a solid magnetic shell and liquid core using microfluidic techniques. The liquid beads consist of a fluorinated oil core and a polymer shell with magnetite particles. The beads are generated in a flow-focusing polydimethylsiloxane (PDMS) device and cured by photo polymerisation. We investigated the response of the liquid beads to an external magnetic field by characterising their motion towards a permanent magnet. Magnetic sorting of liquid beads in a channel was achieved with 90% efficiency. The results show that the liquid beads can be controlled magnetically and have potential applications in digital microfluidics including nucleic acid amplification, drug delivery, cell culture, sensing, and tissue engineering. The present paper also discusses the magnetophoretic behaviour of the liquid bead by varying its mass and magnetite concentration in the shell. We also demonstrated the two-dimensional self-assembly of magnetic liquid beads for potential use in digital polymerase chain reaction and digital loop mediated isothermal amplification.

Calcium alginate elastic capsules for microalgal cultivation.

Calcium alginate elastic capsules with a core-shell structure are versatile spherical solid beads that can be produced in large quantities using various techniques. This type of capsule is a promising platform for cell culture applications, owing to its mechanical elasticity and transparency. This paper reports the production of calcium alginate capsules with high consistency, and for the first time, demonstrates the feasibility of the capsules for microalgal cultivation. Cell growth analysis reveals that the vibrationally-shaken calcium alginate elastic capsule platform yielded a higher maximum cell number (4.86 × 108 cells per mL) during the cultivation period than the control solution platforms. Aquafeed and food supplements for humans are the targeted applications of this novel platform.

Evaluating thrombosis risk and patient-specific treatment strategy using an atherothrombosis-on-chip model.

Platelets play an essential role in thrombotic processes. Recent studies suggest a direct link between increased plasma glucose, lipids, and inflammatory cytokines with platelet activation and aggregation, resulting in an increased risk of atherothrombotic events in cardiovascular patients. Antiplatelet therapies are commonly used for the primary prevention of atherosclerosis. Transitioning from a population-based strategy to patient-specific care requires a better understanding of the risks and advantages of antiplatelet therapy for individuals. This proof-of-concept study evaluates the potential to assess an individual's risk of forming atherothrombosis using a dual-channel microfluidic model emulating multiple atherogenic factors in vitro, including high glucose, high cholesterol, and inflammatory cytokines along with stenosis vessel geometry. The model shows precise sensitivity toward increased plasma glucose, cholesterol, and tumour necrosis factor-alpha (TNF-α)-treated groups in thrombus formation. An in vivo-like dose-dependent increment in platelet aggregation is observed in different treated groups, benefiting the evaluation of thrombosis risk in the individual condition. Moreover, the model could help decide the effective dosing of aspirin in multi-factorial complexities. In the high glucose-treated group, a 50 µM dose of aspirin could significantly reduce platelet aggregation, while a 100 µM dose of aspirin was required to reduce platelet aggregation in the glucose-TNF-α-treated group, which proves the model's potentiality as a tailored tool for customised therapy.

Mesoporous Gold: Substrate-Dependent Growth Dynamics, Strain Accumulation, and Electrocatalytic Activity for Biosensing.

Understanding the growth of mesoporous crystalline materials, such as mesoporous metals, on different substrates can provide valuable insights into the crystal growth dynamics and the redox reactions that influence their electrochemical sensing performance. Herein, it is demonstrated how the amorphous nature of the glass substrate can suppress the typical <111> oriented growth in mesoporous Au (mAu) films. The suppressed <111> growth is manifested as an accumulation of strain, leading to the generation of abundant surface defects, which are beneficial for enhancing the electrochemical activity. The fine structuring attained enables dramatically accelerated diffusion and enhances the electrochemical sensing performance for disease-specific biomolecules. As a proof-of-concept, the as-fabricated glass-grown mAu film demonstrates high sensitivity in electrochemical detection of SARS-CoV-2-specific RNA with a limit of detection (LoD) as low as 1 attomolar (aM).

Correction: Soda et al. Electrochemical Detection of Global DNA Methylation Using Biologically Assembled Polymer Beads. Cancers 2021, 13, 3787.

In the original publication [...].

Recent developments and future perspectives of microfluidics and smart technologies in wearable devices.

Wearable devices are gaining popularity in the fields of health monitoring, diagnosis, and drug delivery. Recent advances in wearable technology have enabled real-time analysis of biofluids such as sweat, interstitial fluid, tears, saliva, wound fluid, and urine. The integration of microfluidics and emerging smart technologies, such as artificial intelligence (AI), machine learning (ML), and Internet of Things (IoT), into wearable devices offers great potential for accurate and non-invasive monitoring and diagnosis. This paper provides an overview of current trends and developments in microfluidics and smart technologies in wearable devices for analyzing body fluids. The paper discusses common microfluidic technologies in wearable devices and the challenges associated with analyzing each type of biofluid. The paper emphasizes the importance of combining smart technologies with microfluidics in wearable devices, and how they can aid diagnosis and therapy. Finally, the paper covers recent applications, trends, and future developments in the context of intelligent microfluidic wearable devices.

Actuation for flexible and stretchable microdevices.

Flexible and stretchable microdevices incorporate highly deformable structures, facilitating precise functionality at the micro- and millimetre scale. Flexible microdevices have showcased extensive utility in the fields of biomedicine, microfluidics, and soft robotics. Actuation plays a critical role in transforming energy between different forms, ensuring the effective operation of devices. However, when it comes to actuating flexible microdevices at the small millimetre or even microscale, translating actuation mechanisms from conventional rigid large-scale devices is not straightforward. The recent development of actuation mechanisms leverages the benefits of device flexibility, particularly in transforming conventional actuation concepts into more efficient approaches for flexible devices. Despite many reviews on soft robotics, flexible electronics, and flexible microfluidics, a specific and systematic review of the actuation mechanisms for flexible and stretchable microdevices is still lacking. Therefore, the present review aims to address this gap by providing a comprehensive overview of state-of-the-art actuation mechanisms for flexible and stretchable microdevices. We elaborate on the different actuation mechanisms based on fluid pressure, electric, magnetic, mechanical, and chemical sources, thoroughly examining and comparing the structure designs, characteristics, performance, advantages, and drawbacks of these diverse actuation mechanisms. Furthermore, the review explores the pivotal role of materials and fabrication techniques in the development of flexible and stretchable microdevices. Finally, we summarise the applications of these devices in biomedicine and soft robotics and provide perspectives on current and future research.

Effect of Honokiol on culture time and survival of Alzheimer's disease iPSC-derived neurons.

Introduction: Patient-derived induced pluripotent stem cells (iPSCs) have been widely used as disease models to test new therapeutic strategies. Moreover, the regenerative potential of stem cells can be improved with the use of biologically active compounds. Our study was designed to explore the effect of honokiol, a small polyphenol molecule extracted from Magnolia officinalis, on the survival and culture time of iPSC-derived neurons from a sporadic Alzheimer's disease (AD) patient. This study aimed to generate iPSCs from peripheral blood mononuclear cells (PBMCs) of an AD patient using episomal plasmids with a nucleofector system and differentiate them into neurons. These iPSC-derived neurons were used to investigate the effect of honokiol extracted from M. officinalis on their survival and long-term cultures. Methods: IPSCs were generated from PBMCs of an AD patient by introducing Oct-3/4, Sox2, Klf4, L-Myc, and Lin28 using NucleofectorTM Technology. Differentiation of neurons derived from iPSCs was carried out using inducers and recognized by biomarkers. The viability of iPSC-derived neurons with the addition of honokiol extracted from the bark of M. officinalis was determined by the MTT analytical kit. Results: IPSCs were generated by reprogramming AD patient-derived PBMCs and subsequently converted into neurons. The survival and growth of iPSC-derived neurons were significantly enhanced by adding honokiol in the experiment conditions. Conclusion: AD iPSC-derived neurons had a high viability rate when cultured in the presence of honokiol. These results have shown that AD iPSC-derived neurons can be an excellent model for screening neurotrophic agents and improving the conditions for long-term cultures of human iPSC-derived neurons. Honokiol proves to be a potential candidate for cellular therapeutics against neurodegenerative disorders.

Instant Candida albicans Detection Using Ultra-Stable Aptamer Conjugated Gold Nanoparticles.

Fungal pathogens such as Candida albicans have significant impacts on women's health and the economy worldwide. Current detection methods often require access to laboratory facilities that are costly, inconvenient, and slow to access. This often leads to self-diagnosis, self-treatment and eventual antifungal resistance. We have created a rapid (within five minutes), cost-effective, and user-friendly method for the early detection of Candida albicans. Our platform utilises aptamer-tagged-gold-core-shell nanoparticles for Candida albicans detection based on the presence of 1,3-ß-d glucan molecules. Nanoparticle aggregation occurs in the presence of Candida albicans fungal cells, causing a redshift in the UV-visible absorbance, turning from pink/purple to blue. This colour change is perceptible by the naked eye and provides a "yes"/"no" result. Our platform was also capable of detecting Candida albicans from individual yeast colonies without prior sample processing, dilution or purification. Candida albicans yeast cells were detected with our platform at concentrations as low as 5 × 105 cells within a 50 µL sample volume. We believe that this technology has the potential to revolutionise women's health, enabling women to test for Candida albicans accurately and reliably from home. This approach would be advantageous within remote or developing areas.

Magnetophoresis-Enhanced Elasto-Inertial Migration of Microparticles and Cells in Microfluidics.

Microfluidic particle and cell manipulation techniques possess many potentials for biomedicine and healthcare. Many techniques have been developed based on active (e.g., electrical, magnetic, acoustic, and thermal) force fields and passive hydrodynamic forces (e.g., inertial and elastic lift forces). However, techniques based on a single active or passive manipulating physics cannot always meet the demands, and combining multiple physics becomes a promising strategy to promote technique flexibility and versatility. In this work, we explored the physical coupling of magnetophoresis with the elastic and inertial (i.e., elasto-inertial) lift forces for the manipulation of microparticles. Particle lateral migration was studied in a coflowing configuration of viscoelastic ferrofluid/water (sample/sheath). The particles were suspended in the viscoelastic ferrofluid and confined near the channel sidewall by a sheath flow. The coordination of magnetophoresis and elasto-inertial lift forces promoted the cross-stream migration of particles. Besides, we investigated the effect of the flow rate ratio and total flow rate on the migration of particles. Furthermore, we also investigated the effects of fluid elasticity in sample and sheath flows on particle migration using different combinations of sample and sheath flows, including Newtonian ferrofluid/water, Newtonian ferrofluid/viscoelastic fluid, and viscoelastic ferrofluid/viscoelastic coflows. Experimental results demonstrated and ascertained the promoted particle lateral migration in the PEO-based ferrofluid/water coflow. Finally, we demonstrate the proof-of-concept application of the physical coupling strategy for cell cross-stream migration and solution exchange. We envisage that this novel multiphysical coupling scheme has great potential for the flexible and versatile manipulation of microparticles and cells.

Viscoelastic microfluidics for enhanced separation resolution of submicron particles and extracellular vesicles.

Manipulation, focusing, and separation of submicron- and nanoparticles such as extracellular vesicles (EVs), viruses and bacteria have broad applications in disease diagnostics and therapeutics. Viscoelastic microfluidic technology emerges as a promising technique, and it shows an unparalleled capacity to manipulate and separate submicron particles in a high resolution based on the elastic effects of non-Newtonian mediums. The maximum particle separation resolution for the reported state-of-the-art viscoelastic microfluidics is around 200 nm. To further enhance the reseparation resolution, this work develops a viscoelastic microfluidic device that can achieve a finer separation resolution up to 100 nm, by optimising the operating conditions such as flow rate, flow rate ratio and polyethylene oxide (PEO) concentration. With these optimised conditions, we separated a ternary mixture of 100 nm, 200 nm and 500 nm polystyrene particles, with purities above 90%, 70% and 82%, respectively. Furthermore, we also applied the developed viscoelastic microfluidic device for the separation of cancer cell-secreted extracellular vesicles (EVs) into three different size groups. After single processing, the separation efficiencies for small EVs (sEVs, <150 nm), medium EVs (mEVs, 150-300 nm), and large EVs (>300 nm) were 86%, 80% and 50%, respectively. The enrichment factors for the three EV groups were 2.4, 1.1 and 1.3, respectively. Moreover, we observed an unexpected effect of high PEO concentrations (2000-5000 ppm) on the lateral migration of nanoparticles where nanoparticles of up to 50 nm surprisingly can migrate and concentrate at the middle of the microchannel. This simple and label-free viscoelastic microfluidic device possesses excellent potential for sorting submicron particles for various chemical, biological, medical and environmental applications.

Unravelling Surface Modification Strategies for Preventing Medical Device-Induced Thrombosis.

The use of biomaterials in implanted medical devices remains hampered by platelet adhesion and blood coagulation. Thrombus formation is a prevalent cause of failure of these blood-contacting devices. Although systemic anticoagulant can be used to support materials and devices with poor blood compatibility, its negative effects such as an increased chance of bleeding, make materials with superior hemocompatibility extremely attractive, especially for long-term applications. This review examines blood-surface interactions, the pathogenesis of clotting on blood-contacting medical devices, popular surface modification techniques, mechanisms of action of anticoagulant coatings, and discusses future directions in biomaterial research for preventing thrombosis. In addition, this paper comprehensively reviews several novel methods that either entirely prevent interaction between material surfaces and blood components or regulate the reaction of the coagulation cascade, thrombocytes, and leukocytes.

Facile Fabrication of "Tacky", Stretchable, and Aligned Carbon Nanotube Sheet-Based Electronics for On-Skin Health Monitoring.

Point-of-care monitoring of physiological signals such as electrocardiogram, electromyogram, and electroencephalogram is essential for prompt disease diagnosis and quick treatment, which can be realized through advanced skin-worn electronics. However, it is still challenging to design an intimate and nonrestrictive skin-contact device for physiological measurements with high fidelity and artifact tolerance. This research presents a facile method using a "tacky" surface to produce a tight interface between the ACNT skin-like electronic and the skin. The method provides the skin-worn electronic with a stretchability of up to 70% strain, greater than that of most common epidermal electrodes. Low-density ACNT bundles facilitate the infiltration of adhesive and improve the conformal contact between the ACNT sheet and the skin, while dense ACNT bundles lessen this effect. The stretchability and conformal contact allow the ACNT sheet-based electronics to create a tight interface with the skin, which enables the high-fidelity measurement of physiological signals (the Pearson's coefficient of 0.98) and tolerance for motion artifacts. In addition, our method allows the use of degradable substrates to enable reusability and degradability of the electronics based on ACNT sheets, integrating "green" properties into on-skin electronics.

Field effect transistor based wearable biosensors for healthcare monitoring.

The rapid advancement of wearable biosensors has revolutionized healthcare monitoring by screening in a non-invasive and continuous manner. Among various sensing techniques, field-effect transistor (FET)-based wearable biosensors attract increasing attention due to their advantages such as label-free detection, fast response, easy operation, and capability of integration. This review explores the innovative developments and applications of FET-based wearable biosensors for healthcare monitoring. Beginning with an introduction to the significance of wearable biosensors, the paper gives an overview of structural and operational principles of FETs, providing insights into their diverse classifications. Next, the paper discusses the fabrication methods, semiconductor surface modification techniques and gate surface functionalization strategies. This background lays the foundation for exploring specific FET-based biosensor designs, including enzyme, antibody and nanobody, aptamer, as well as ion-sensitive membrane sensors. Subsequently, the paper investigates the incorporation of FET-based biosensors in monitoring biomarkers present in physiological fluids such as sweat, tears, saliva, and skin interstitial fluid (ISF). Finally, we address challenges, technical issues, and opportunities related to FET-based biosensor applications. This comprehensive review underscores the transformative potential of FET-based wearable biosensors in healthcare monitoring. By offering a multidimensional perspective on device design, fabrication, functionalization and applications, this paper aims to serve as a valuable resource for researchers in the field of biosensing technology and personalized healthcare.

Maximising Affordability of Real-Time Colorimetric LAMP Assays.

Molecular diagnostics have become indispensable in healthcare, agriculture, and environmental monitoring. This diagnostic form can offer rapid and precise identification of pathogens and biomarkers. However, traditional laboratory-based molecular testing methods can be expensive and require specialised training, limiting their accessibility in resource-limited settings and on-site applications. To overcome these challenges, this study proposes an innovative approach to reducing costs and complexity in portable colorimetric loop-mediated isothermal amplification (LAMP) devices. The research evaluates different resistive heating systems to create an energy-efficient, cost-effective, and compact device to heat a polydimethylsiloxane (PDMS) block for precise temperature control during LAMP reactions. By combining this novel heating system with an off-the-shelf red-green-blue (RGB) sensor to detect and quantify colour changes, the integrated system can accurately detect Leifsonia xyli subsp. xyli, the bacteria responsible for ratoon stunting disease (RSD) in sugarcane. The experimental validation of this system demonstrates its ability to detect the target pathogen in real time, making it an important development for low cost, portable, and easy-to-use molecular diagnostics in healthcare, agriculture, and environmental monitoring applications.

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method.

Currently, the treatment for acute disease encompasses the use of various biological drugs (BDs). However, the utilisation of BDs is limited due to their rapid clearance and non-specific accumulation in unwanted sites, resulting in a lack of therapeutic efficacy together with adverse effects. While nanoparticles are considered good candidates to resolve this problem, some available polymeric carriers for BDs were mainly designed for long-term sustained release. Thus, there is a need to explore new polymeric carriers for the acute disease phase that requires sustained release of BDs over a short period, for example for thrombolysis and infection. Poly(succinimide)-oleylamine (PSI-OA), a biocompatible polymer with a tuneable dissolution profile, represents a promising strategy for loading BDs for sustained release within a 48-h period. In this work, we developed a two-step nanoprecipitation method to load the model protein (e.g. bovine serum albumin and lipase) on PSI-OA. The characteristics of the nanoparticles were assessed based on various loading parameters, such as concentration, stirring rate, flow rate, volume ratio, dissolution and release of the protein. The optimised NPs displayed a size within 200 nm that is suitable for vasculature delivery to the target sites. These findings suggest that PSI-OA can be employed as a carrier for BDs for applications that require sustained release over a short period.

Doubly committed ventricular septal defect: Is it safe to perform surgical closure through the pulmonary trunk approached by right vertical axillary thoracotomy?

Objective: This study investigated the safety of performing surgical repair for doubly committed ventricular septal defects by right vertical infra-axillary minithoracotomy (RVIAT). Methods: A retrospective comparative study was performed to evaluate the outcomes of patients who underwent doubly committed ventricular septal defects closure from January 2019 to May 2022. Seventy-four patients were enrolled in the study and treated with either the median sternotomy approach (MSA: n = 37) or the RVIAT approach (RVIAT: n = 37). Results: The median weight and age in the MSA group were significantly lower than those in the RVIAT group (MSA: 6.0 kg [interquartile range] (IQR), 5.2 to 8.7 kg] vs RVIAT: 7.5 kg [IQR, 5.6-14 kg]; P = .034 and MSA: 4.9 months [IQR, 3.6-9.4 month] vs 9.6 months [IQR, 5.0-60.4 months]; P = .0084). No patients died, and no patients in the RVIAT group required conversion to the MSA approach. The mean prebypass surgical time was longer in the RVIAT group (36.1 ± 8.2 minutes vs 31.8 ± 5.6 minutes; P = .03). There were no significant differences between the 2 groups in cardiopulmonary bypass time, aortic crossclamp time, or operation time. Significantly shorter ventilation times were observed in the RVIAT group (11.9 ± 8.2 hours vs 15.4 ± 6.3 hours; P = .006). Conclusions: Closure of doubly committed ventricular septal defects through the pulmonary trunk by the RVIAT approach is feasible and safe, and does not increase the risk of bypass-related complications.

Physicochemical properties and interactions of perfluoroalkyl substances (PFAS) - Challenges and opportunities in sensing and remediation.

Per- and polyfluoroalkyl substances (PFAS) is a class of persistent organic pollutants that presents health and environmental risks. PFAS are ubiquitously present in the environment, but current remediation technologies are ineffective in degrading them into innocuous chemicals, especially high energy degradation processes often generate toxic short chain intermediates. Therefore, the best remediation strategy is to first detect the source of pollution, followed by capturing and mineralising or recycling of the compounds. The main objective of this article is to summarise the unique physicochemical properties and to critically review the intermolecular and intramolecular physicochemical interactions of PFAS, and how these interactions can become obstacles; and at the same time, how they can be applied to the PFAS sensing, capturing, and recycling process. The physicochemical interactions of PFAS chemicals are being reviewed in this paper includes, (1) fluorophilic interactions, (2) hydrophobic interactions, (3) electrostatic interactions and cation bridging, (4) ionic exchange and (5) hydrogen bond. Moreover, all the different influential factors to these interactions have also been reported. Finally, properties of these interactions are compared against one another, and the recommendations for future designs of affinity materials for PFAS have been given.

Protein array processing software for automated semiquantitative analysis of serum antibody repertoires.

Effective immunotherapies activate natural antitumor immune responses in patients undergoing treatment. The ability to monitor immune activation in response to immunotherapy is critical in measuring treatment efficacy over time and across patient cohorts. Protein arrays are systematically arranged, large collections of annotated proteins on planar surfaces, which can be used for the characterization of disease-specific and treatment-induced antibody repertoires in individuals undergoing immunotherapy. However, the absence of appropriate image analysis and data processing software presents a substantial hurdle, limiting the uptake of this approach in immunotherapy research. We developed a first, automated semiquantitative open-source software package for the analysis of widely used protein macroarrays. The software allows accurate single array and inter-array comparative studies through the tackling of intra-array inconsistencies arising from experimental disparities. The innovative and automated image analysis process includes adaptive positioning, background identification and subtraction, removal of null signals, robust statistical analysis, and protein pair validation. The normalized values allow a convenient semiquantitative data analysis of different samples or timepoints. Enabling accurate characterization of sample series to identify disease-specific immune profiles or their relative changes in response to treatment may serve as a diagnostic or predictive tool of disease.