Jeroen C. Vollenbroek

Current hemodialysis (HD) methods inefficiently remove protein-bound uremic toxins (PBUTs) due to their high binding affinity to plasma proteins, mainly albumin. This study aimed to investigate electromagnetic (EM) fields and temperature as potential extracorporeal, non-systemic methods to increase HD PBUT clearance. PBUT release was measured in infusible (caprylate-stabilized) albumin solutions spiked with indoxyl sulfate (IS) using an in vitro dialysis setup including a real-time, in-line IS-sensor. No measurable influence on PBUT release was observed during EM field-tests (f = 1–600 MHz, E <= 1 kV/m), but temperature tests (35–40 °C range) showed an absolute increase in IS free fraction of 0.7%/°C. Furthermore, static equilibrium dialysis tests, including IS, p-cresyl sulfate (pCS) and hippuric acid (HA), showed a free fraction increase for all three PBUTs upon a temperature increase from 37 °C to 43 °C (IS 1.30-fold, pCS 1.12-fold, HA 1.15-fold). Mathematical modeling showed a 1.14-fold decrease in plasma IS concentration after 5 weeks of HD, and exploratory hemocompatibility tests did not reveal pronounced changes over 15 heating cycles at 43 °C under static conditions. Extracorporeal temperature elevation is a promising technique to enhance PBUT removal during hemodialysis, which may be easily combined with current HD machines, does not break sterility, and avoids elevating free PBUTs inside the body.

Human serum albumin (HSA) is the most abundant plasma protein and plays essential roles in regulating oncotic pressure, transporting endogenous and exogenous compounds, and maintaining redox balance. Because of its biochemical properties, HSA is widely used in clinical medicine, biotechnology, and pharmaceutical development. However, albumin is not a static molecule. It undergoes numerous post-translational modifications (PTMs), including oxidation, glycation, carbonylation, carbamylation, and aggregation, which can significantly alter its structure, ligand-binding properties, antioxidant capacity, and pharmacokinetics. Furthermore, commercial albumin products exhibit substantial heterogeneity arising from differences in source material, manufacturing processes, formulation conditions, and storage practices. This review summarizes the current understanding of PTMs affecting human serum albumin, with particular emphasis on their molecular origins and functional implications. We discuss how physiological, pathological, and manufacturing-induced modifications influence albumin activity and contribute to variability among commercial albumin products. In addition, we examine established and emerging applications of PTM-modified albumin in diagnostics, critical care, extracorporeal detoxification, drug delivery, nanomedicine, and regenerative medicine. Finally, we highlight current challenges related to product heterogeneity, quality control, regulatory assessment, and discuss future opportunities in albumin-based technologies. A deeper understanding of albumin PTMs is essential for improving critical care and developing next-generation albumin-based biomedical products.

Miniaturisation of artificial organs to an implantable form factor is one of the great challenges in biomedical engineering. Most patients with end-stage kidney failure depend on dialysis, yet dialysis remains burdensome. An implantable artificial kidney would be a paradigm shift that would largely replace the need for dialysis. By coupling the joint constraints on hemocompatibility, hemodynamics, and epithelial transport to boundary conditions, such as the pressure and shear stress imposed by the human body, we show that: (i) blood compatibility requires centimetre-scale blood-distribution manifolds and preferably endothelialised channels; (ii) concentration polarisation and hemoconcentration limit filtration performance, causing diminishing returns from higher membrane permeability; (iii) hemodynamics and packing constraints drive local channels toward capillary-scale dimensions; and (iv) proximal-tubule-only architectures cannot satisfy sodium, potassium, phosphate, and water balance without shifting a large homeostatic burden to the patient. This necessitates multiple epithelial modules requiring ∼ 1.15 m² of active surface area and ∼ 250 layers and makes near-kidney proximal-tubule transport capacity a prerequisite for geometric feasibility. Together, our results show that the minimally viable artificial kidney is still constrained to a kidney-scale, macro-to-micro architecture. This conclusion applies not only to synthetic scaffold-based designs, but also to biological and hybrid strategies in which cells participate in architecture formation, since all such routes must satisfy the same coupled requirements.

Haemodialysis is highly resource-intensive and generates substantial environmental waste. Each treatment can produce up to 8 kg of plastic and biohazardous waste per session and cumulatively yields multiple tonnes of CO₂-eq emissions per patient per year. To address this burden, nephrology guidelines now emphasise life cycle assessment (LCA) strategies to reduce healthcare's carbon footprint. We evaluated two low-cost operational changes: (1) replacing a standard sterile access kit with non-sterile materials for aseptic arteriovenous access cannulation, and (2) automating bloodline and dialyser drainage to improve the sustainability of routine dialysis - two interventions grounded in guideline-supported aseptic technique, though clinical outcomes were not formally assessed in this study. At the University Medical Centre Utrecht dialysis unit (Netherlands), we performed a comparative cradle-to-grave LCA following ISO 14,040/44 standards. The interventions were: (1) replacing the disposable sterile vascular access kit with Kleenex-brand non-sterile protection sheets plus Klinipress compresses (aseptic working procedure); and (2) configuring the dialysis machines to automatically drain and retain spent bloodlines and dialysers before disposal. Using the EU's Environmental Footprint v3.1 (EF 3.1) impact method, we quantified the changes in environmental impact across categories (e.g. climate change, ecotoxicity, energy use) relative to standard practice. The LCA showed that the Kleenex/Klinipress substitution reduced impacts across all environmental categories. Compared to the conventional sterile kit, environmental burdens were up to 87% lower (including carbon footprint, freshwater ecotoxicity, and cumulative energy demand) for the non-sterile Kleenex/Klinipress. Automated drainage of the extracorporeal circuit also lowered impacts: climate change impact per session decreased by more than 9%, and freshwater ecotoxicity by about 8%, owing to reduced infectious waste volume. This case study demonstrates that routine haemodialysis can be made substantially greener through practical workflow changes. Substituting sterile kits for non-sterile consumables, and draining dialysis sets before disposal, led to major reductions in waste and carbon emissions, without requiring additional infrastructure or deviation from established clinical workflows. These findings highlight simple yet effective actionable strategies for dialysis centres to advance healthcare sustainability goals: by applying existing technologies and process changes, clinics can markedly shrink their carbon footprint while remaining consistent with current evidence-based clinical guidelines.

The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In this review, PBUT removal with current state-of-the-art dialysis technologies and future perspectives are discussed. Strategies to enhance PBUT clearance include methods that interfere with PBUT–albumin binding, such as chemical displacers, high ionic strength, pH changes, or electromagnetic fields, thereby increasing the free fraction available for dialysis. While these methods have shown promise in vitro, and some also in vivo, long-term safety data are lacking. PBUT removal can also be increased by adsorption, either directly via hemoperfusion, or indirectly, e.g., via sorbents incorporated in a mixed-matrix membrane or dissolved in the dialysate. In the kidney, PBUTs are secreted in the proximal tubules; hence, a cell-based bioartificial kidney (BAK) that secretes PBUTs is proposed as an add-on to current dialysis. Yet both PBUT adsorption strategies and, in particular, BAKs face considerable challenges in upscaling and mass production at acceptable costs. In conclusion, many novel technologies are under development, all requiring further (pre)clinical testing and upscaling before these strategies can be applied in the clinic.

The use of microfluidics for analysis of biological and chemical compounds is flourishing, with droplet microfluidics being well suited for high-throughput single substance analysis. Nowadays, many new experimental set-ups are reported that combine various fields and expertise, including, among others, microfluidics, optics, electronics, chemistry, biology, etc. This work aims to highlight the engineering effort that goes into the development and realization of experimental set-ups for obtaining ‘good’ scientific data. High quality research and results stand or fall with the quality of the set-ups that are used for obtaining said results. Unfortunately, replication of these custom-made set-ups (as well as reproducibility/gathering of data) may be hampered if not all parts are sufficiently/detailed documented in the (Electronic) Supplementary Information ((E)SI). In this work, we present detailed descriptions of the fluidic, electronic, and optical interfacings that are developed to make a microfluidic platform for the high-throughput, fluorescent-based screening of Fluidic Catalytic Cracking (FCC) catalyst particle acidity and the subsequent sorting of the most active catalyst particles.

Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs.

The particles of heterogeneous catalysts differ greatly in size, morphology, and most importantly, in activity. Studying these catalyst particles in batch typically results in ensemble averages, without any information at the level of individual catalyst particles. To date, the study of individual catalyst particles has been rewarding but is still rather slow and often cumbersome¹. Furthermore, these valuable in-depth studies at the single particle level lack statistical relevance. Here, we report the development of a droplet microreactor for high-throughput fluorescence-based measurements of the acidities of individual particles in fluid catalytic cracking (FCC) equilibrium catalysts (ECAT). This method combines systematic screening of single catalyst particles with statistical relevance. An oligomerization reaction of 4-methoxystyrene, catalyzed by the Brønsted acid sites inside the zeolite domains of the ECAT particles, was performed on-chip at 95 °C. The fluorescence signal generated by the reaction products inside the ECAT particles was detected near the outlet of the microreactor. The high-throughput acidity screening platform was capable of detecting ~1000 catalyst particles at a rate of 1 catalyst particle every 2.4 s. The number of detected catalyst particles was representative of the overall catalyst particle population with a confidence level of 95%. The measured fluorescence intensities showed a clear acidity distribution among the catalyst particles, with the majority (96.1%) showing acidity levels belonging to old, deactivated catalyst particles and a minority (3.9%) exhibiting high acidity levels. The latter are potentially of high interest, as they reveal interesting new physicochemical properties indicating why the particles were still highly acidic and reactive.