“Rapid prototyping of flexible biodegradable ECoG arrays for high-resolution cortical mapping and real-time seizure classification ”

Adrenocortical carcinoma (ACC) is a rare malignancy arising from the adrenal cortex. While ACC can be associated with adrenal hormone excess syndromes, classic paraneoplastic syndromes are rarely seen. Stauffer syndrome, a paraneoplastic phenomenon characterized by reversible cholestasis in the absence of liver metastases, has been described with renal carcinoma and other malignancies but has not been previously reported in ACC. A 38-year-old man presented with emesis, painless jaundice, pruritus, and weight loss. Laboratory evaluation demonstrated elevated total bilirubin of 8.7 mg/dL (N < 1.3 mg/dL). Computed tomography revealed a 20.4-cm left adrenal mass without evidence of liver metastases. The patient's condition deteriorated rapidly with progressive renal failure and worsening hyperbilirubinemia. The patient underwent left adrenalectomy, nephrectomy, ureterolysis, and wedge liver biopsy. Histopathology showed necrotic ACC with tumor invasion into the adrenal capsule, no lymphovascular invasion, uninvolved margins, and Ki-67 of 40%. Kidney parenchyma exhibited diffuse pigment casts. The liver specimen contained diffuse bile deposits and minimal chronic inflammation in the portal tracts. He tested positive for the pathogenic variant of folliculin (FLCN) gene consistent with Birt-Hogg-Dube syndrome. Renal function recovered after surgery, and bilirubin level normalized after several weeks. Based on clinical presentation and absence of other etiologies, reversible cholestatic jaundice was attributed to Stauffer syndrome. This is the first report of a unique presentation of paraneoplastic-related hyperbilirubinemia in the setting of ACC. While extremely rare, Stauffer syndrome should still be considered in differential diagnosis in patients with ACC with liver dysfunction and jaundice without evidence of liver metastases.

ZnO is a material that has gained a great deal of interest in the low-temperature fabrication of high-mobility transistors. For rapid prototyping of device structures, as well as cycle time reduction for investigations of processing/geometry interactions, a maskless process with high spatial accuracy is desired. High-mobility ZnO transistors were fabricated on glass using a laser-thermal-based maskless patterning process to generate working circuits. All deposition temperatures were below 200 &#xB0;C, allowing this process to be compatible with polymeric supports. A variety of circuits using 5 &#x3BC;m design rules and various channel width and length dimensions (w/l) were fabricated and analyzed. The circuits demonstrated included ring oscillators and logic circuits, such as an exclusive OR made from NANDs and NORs. The ring oscillator frequency was demonstrated to be about 20 kHz at 20 V. An active-matrix backplane was fabricated and used to drive an OLED device. The operating characteristics of the transistors, circuits, and processes were found to be interrelated and need to be co-optimized for the best performance.

The sensor, designed to be worn directly on the skin, is suitable for real-time monitoring of the recovery level of not only general wounds, but also difficult-to-heal wounds, such as those with chronic inflammation. Notably, healthy skin has a pH range of 4–6. When a wound occurs, the pH is known to be approximately 7.4. In this study, alpha-naphtholphthalein (Naph) was immersed in a cotton-blended textile to produce a wearable halochromic sensor that clearly changed color depending on the pH of the skin in the range 6–9, including pH 7.4, which is the skin infection state. The coating was performed without using an organic solvent by dissolving it in micelle form using cetyltrimethylammonium bromide, a surfactant, in water. Naph-based halochromic sensor shows light yellow, which is the dye’s own color, at pH 6, which is a healthy skin condition, and gradually showed a clear color change to light green-green-blue as pH increased. Even after washing and drying by rubbing with regular tap water, the color change due to pH was maintained more than 10 times. Naph-based halochromic sensors use a simple solution production and coating method and are not only reusable sensors that can be washed with water but also use environmentally friendly water, making them very suitable for developing commercial products for wound pH monitoring. In addition, it can be easily applied to medical supplies, such as medical gauze, patient clothes, and compression bandages, as well as everyday wear, such as clothing, gloves, and socks. Therefore, it is expected to be widely used as a wound pH sensor, allowing real-time monitoring of the skin condition of individuals with chronic skin inflammation, including patients requiring wound recovery.

Millimeter-wave 3D-printed filtering power divider with high frequency selectivity and enhanced heat dispersion

Capacitive sensors are common ubiquitous sensing devices that permeate through many industries. The overwhelming majority of touchscreens use capacitive sensor arrays for the precise detection of touch. Many MEMS sensors use capacitance as the variable that is manipulated to detect the sensed parameter (e.g. accelerometers). However, the use of non-rigid, ambient, or custom capacitive sensor arrays has not seen the same level of adoption. CSAs (capacative sensor arrays) can be made from a wide array of materials and techniques-including 3d printing and laser ablation-to rapidly create CSAs that can be custom fit to enable proximity, force, and touch detection. This work investigates some of these materials and how they can be fabricated in a laboratory environment with a single robotic arm.

We present the rapid prototyping of electrochemical sensor arrays integrated to microfluidics towards the fabrication of integrated microsystems prototypes for point-of-care diagnostics. Rapid prototyping of microfluidics was realised by high-precision milling of polycarbonate sheets, which offers flexibility and rapid turnover of the desired designs. On the other hand, the electrochemical sensor arrays were fabricated using standard photolithographic and metal (gold and silver) deposition technology in order to realise three-electrode cells comprising gold counter and working electrodes as well as silver reference electrode. The integration of fluidic chips and electrode arrays was realised via a laser-machined double-sided adhesive gasket that allowed creating the microchannels necessary for sample and reagent delivery. We focused our attention on the reproducibility of the electrode array preparation for the multiplexed detection of tumour markers such as carcinoembryonic antigen and prostate-specific antigen as well as genetic breast cancer markers such as estrogen receptor-alpha, plasminogen activator urokinase receptor, epidermal growth factor receptor and erythroblastic leukemia viral oncogene homolog 2. We showed that by carefully controlling the electrode surface pre-treatment and derivatisation via thiolated antibodies or short DNA probes that the detection of several key health parameters on a single chip was achievable with excellent reproducibility and high sensitivity.

Microfluidic device prototyping demands rapid, cost-effective, and high-precision mould fabrication, yet ultrashort pulsed laser structuring of polymer inserts remains underexplored. This study presents a novel method for fabricating microfluidic mould inserts using femtosecond (fs) laser ablation of polyimide (PI) films, achieving high precision from design to prototype. PI films (250 µm) were structured using a 355 nm fs laser (300 fs, 500 kHz, 0.95 J/cm2) in a photochemically dominated ablation regime and bonded to reusable steel plates. Injection moulding trials with cyclic olefin copolymer (COC) and polymethyl methacrylate (PMMA) were conducted with diverse designs, including concentration gradient generators (CGG), organ-on-chip (OOC) with 20 µm bridges, and double emulsion droplet generators (DEDG) with 100–500 µm channels, ensuring robustness across complex geometries. The method achieved near 1:1 replication (errors &lt; 2%, microchannel height tolerances &lt; 1%, Sa = 0.02 µm in channels, 0.26 µm in laser-structured areas), machining times under 2 h, and mould durability over 100 cycles without significant deterioration. The PI’s heat-retarding effect mimicked variothermal moulding, ensuring complete micro-penetration without specialised equipment. By reducing material costs using PI films and reusable steel plates, enabling rapid iterations within hours, and supporting industry-compatible prototyping, this approach lowers barriers for small-scale labs. It enables rapid prototyping of diagnostic lab-on-chip devices and supports decentralised manufacturing for biomedical, chemical, and environmental applications, offering a versatile, cost-effective tool for early-stage development.

The reliable and cost-effective fabrication of 2D and 3D structured nano-surfaces is prerequisite for a number of industrial and emerging applications: (i) leading-edge complex masks, (ii) high precision nano-imprint templates, (iii) nano-functionalized surfaces and 3D structures for applications in nano-photonics, nano-magnetics, and nano-biotechnology. Projection Mask-Less Patterning (PMLP) is based on many hundred thousands of ion beams working in parallel. A PMLP proof-of-concept tool has been realized as part of the European project CHARPAN (Charged Particle Nanotech; www.charpan.com). The novel ion beam projection optics with 200x reduction shows 16nm half pitch resolution. First results with a programmable aperture plate system have been achieved demonstrating high accuracy and flexible pattern fabrication.

Fully Biological Bioprinted Blood Vessel Substitutes

Neuromodulation through implantable pulse generators (IPGs) represents an important treatment approach for neurological disorders. While the field has observed the success of state-of-the-art interventions, such as deep brain stimulation (DBS) or responsive neurostimulation (RNS), implantable systems face various technical challenges, including the restriction of recording from a limited number of brain sites, power management, and limited external access to the assessed neural data in a continuous fashion. To the best of our knowledge, for the first time in this study, we investigated the feasibility of recording human intracranial EEG (iEEG) using a benchtop version of the Brain Interchange (BIC) unit of CorTec, which is a portable, wireless, and externally powered implant with sensing and stimulation capabilities. We developed a MATLAB/SIMULINK-based rapid prototyping environment and a graphical user interface (GUI) to acquire and visualize the iEEG captured from all 32 channels of the BIC unit. We recorded prolonged iEEG (~ 24 h) from three human subjects with externalized depth leads using the BIC and commercially available clinical amplifiers simultaneously in the epilepsy monitoring unit (EMU). The iEEG signal quality of both streams was compared, and the results demonstrated a comparable power spectral density (PSD) in all the systems in the low-frequency band (< 80 Hz). However, notable differences were primarily observed above 100 Hz, where the clinical amplifiers were associated with lower noise floor (BIC-17 dB vs. clinical amplifiers < − 25 dB). We employed an established spike detector to assess and compare the spike rates in each iEEG stream. We observed over 90% conformity between the spikes rates and their spatial distribution captured with BIC and clinical systems. Additionally, we quantified the packet loss characteristic in the iEEG signal during the wireless data transfer and conducted a series of simulations to compare the performance of different interpolation methods for recovering the missing packets in signals at different frequency bands. We noted that simple linear interpolation has the potential to recover the signal and reduce the noise floor with modest packet loss levels reaching up to 10%. Overall, our results indicate that while tethered clinical amplifiers exhibited noticeably better noise floor above 80 Hz, epileptic spikes can still be detected successfully in the iEEG recorded with the externally powered wireless BIC unit opening the road for future closed-loop neuromodulation applications with continuous access to brain activity.

The reconstruction of complex soft tissues, such as urethral and nerve tissues, requires constructs that integrate vascularization, lumen integrity, and innervation with clinically relevant mechanical and biophysical properties. Current tissue-engineered tubular constructs often fail due to limited strength, instability under physiological conditions, and insufficient electroactivity. This study demonstrates the unique role of carbon nanofibers (CNFs) in improving the structural fidelity of alginate-gelatin hydrogels for additive manufacturing (3D extrusion printing) and clinical applicability. CNF incorporation improved gel strength, viscoelasticity, printability, and buildability while tailoring stretchability, compressibility, swelling, degradation, antimicrobial activity, vascularization, and inflammatory response in 3D-printed scaffolds. In the 3.5D printing approach, the rapid transformation of flat sheets of the CNF-reinforced hydrogel inks to customized tubular constructs with lumen patency was accomplished. At 0.75% CNF addition, hydrogel inks showed a 1.57- and 2.5-fold improvement in viscoelastic range with respect to shear stress and shear strain and a 1.2-fold increase in elastic recoverability, alongside a 3.6-fold enhancement in fracture stress and a 2-fold increase in elastic modulus under uniaxial tension, and the highest electrical conductivity of 0.5 S/m. Micro-CT confirmed interconnected porous structures with pore volume fraction and pore tortuosity of 0.74 and 1.09, respectively. At the same time, the as-printed tubular grafts (3.8 cm in length, 3 mm internal diameter) exhibited smooth luminal surfaces (∼44-100 nm roughness). NIH-3T3 fibroblasts maintained >80% viability, while antimicrobial analysis revealed strong activity against E. coli and S. aureus. In vivo study in Wistar rats revealed normal regulation of different immune cell markers such as CD8, CD68, TNF-α, COX-2, and IL-6, shifting from acute to chronic inflammation and an ehnacement in vascularization by 30 days as evident from H&E, MTS, and vWF straining. No systemic toxicity in the vital organs was recorded. Collectively, these findings highlight CNF-reinforced alginate-gelatin hydrogels can serve as electroconductive, mechanically robust, and biologically responsive scaffolds with a translational potential for complex soft tissue regeneration.

Highly conformal and mechanically robust curvy electronics that seamlessly adapt to sophisticated and unpredictable 3D geometries provide breakthrough solutions in advanced fields such as health monitoring, wireless energy transmission, and human-computer interface. Nevertheless, existing material choices along with manufacturing techniques substantially impede these electronics from achieving their full potential. This study presents a mask-free and straightforward direct writing and transfer (DW&T) technique that employs a polytetrafluoroethylene film as a temporary substrate, utilizing the phase transition of printed electrodes between hydrogel and dry states to enable cost-effective fabrication of conformally adhering conductive microelectrode patterns on nearly all 3D surfaces. The resultant microelectrodes demonstrate extensively adjustable feature dimensions (linewidth 50-400 µm; height 0.07-2.3 µm; pitch 20 µm in minimum) and possess distinct electrical and optical characteristics, in addition to exhibiting significant stability under severe bending and stretching strains and recyclability. To demonstrate the capabilities of the DW&T, imperceptible and customizable substrate-free electronic skin (e-skin) on human skin is developed. The e-skin maintains ultraconformal and seamless contact with the skin, does not impede the natural sensations and physiological changes of its hosts, and achieves high-fidelity recording of diverse electrophysiological signals.

Quick and easy prototyping methods are beneficial for accelerated product development, allowing for concepts to be realised through quick experimentation, validating predictions based on theory and modelling. A rapid subtractive method for the fabrication of metallic antennas, using laser ablation is reported here. These antennas may be designed for a wide range of wireless power reception applications, as integral parts of a powered device. In line with typical application in sub-dermal implants, we designed the antennas in this work to operate at distances similar to that of the dermis. Inductive spiral coil designs are fabricated from gold on a biocompatible soft polymer, Polydimethylsiloxane (PDMS). PDMS has low dielectric constant of 2.32-2.40 and low loss tangent of 0.04-0.06, which is advantageous for use as antenna substrate. The fabricated inductive coils on PDMS are characterized through electrical impedance spectroscopy and tested as a wireless signal receiver, coupled with a Qi standard wireless transmitting module, at an operating frequency of 100 kHz. Importantly, the fabricated coils show resonance in the operational frequency range of the Qi standard (100 kHz to 125 kHz). This is the first instance of laser ablation defined spiral antennas on biocompatible elastomeric substrates. Although the PDMS based inductive coils have high impedance of 2800 ± 300 Ω at 100 kHz, owing to the mechanical mismatch of rigid conductor and flexible substrate, this approach shows promise. Furthermore, strategies to decrease the impedance of such PDMS-based devices are also discussed.

The invasive nature of brain implants remains a major limitation in neuromodulation strategies, often leading to chronic inflammation. To address this, soft coatings are applied on rigid probes to reduce the mechanical mismatch at the interface, or flexible probes are implemented accompanied by temporary stiffeners. This study presents a hybrid strategy integrating both approaches by applying a permanent hydrogel coating onto flexible neural probes. Moreover, we utilise the applied coatings as tool for post-operative non-invasive imaging via functionalisation of the hydrogel with 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), a monomer that increases radiodensity. Rheological measurements confirmed that AATIPA incorporation did not significantly alter the hydrogels' mechanical properties (storage moduli ranging from 139 ± 33.5 to 186 ± 55.5 kPa). Subsequently, we show that coated flexible probes exhibited a two-fold increase in critical buckling force compared to uncoated counterparts, indicating improved mechanical robustness evidenced through enhanced insertion performance in agarose brain phantoms. The mechanical contrast supports the dual purpose of the material in our application: the coatings provide stiffness to facilitate probe insertion in the dry state, while transitioning to a compliant, soft interface upon swelling, post-implantation. Finally, the radiodense coating enabled successful visualization of the probes in the hippocampus of a mouse model using μ-CT imaging. This approach offers a promising route for improving the mechanical and imaging performance of neural implants, potentially reducing reliance on post-mortem histology and enhancing real-time feedback in neuromodulation research.