Ali Douaki

Early diagnosis of hepatocellular carcinoma (HCC) still represents a significant challenge, particularly in the context of etiological shift toward obesity and non-viral liver disease-associated HCC. Through intersection-based analysis of independent transcriptomic datasets comprising healthy controls, individuals with obesity or NAFLD, and HCC patients with viral or non-viral etiologies, we prioritized ADAMTS3, a secreted protein, for further investigation of its functional and mechanistic relevance to HCC. ADAMTS3 was upregulated in HCC and demonstrated transcriptomic discrimination between HCC and non-HCC populations. Notably, in the validation cohort, ADAMTS3 retained discriminative capacity in clinically defined alpha-fetoprotein-negative HCC patients. Functionally, ADAMTS3 knockdown impaired cell proliferation, clonogenicity, and migration, while inducing apoptosis and cell-cycle arrest. Reintroduction of ADAMTS3 partially rescued these cellular effects. Mechanistically, ADAMTS3 promotes HCC cell growth and migration through TGF-β:TGFBR2 signaling. ADAMTS3 knockdown increased extracellular TGF-β and downstream SMAD phosphorylation. Neutralization of extracellular TGF-β alleviated growth inhibition caused by ADAMTS3 knockdown. Consistently, TGFBR2 knockdown partially restored the cell growth and migration suppressed by ADAMTS3 knockdown. We also developed a DNA origami-based SERS aptasensor targeting ADAMTS3, achieving highly sensitive detection of ADAMTS3 down to 10⁻¹² M with strong quantitative capability (R² = 0.914). Together, our findings support a role for ADAMTS3 in promoting HCC cell growth and migration and provide a basis for further investigation of its relevance to HCC biomarker development. The DNA origami-based SERS aptasensor provides a sensitive analytical approach for future studies of circulating or serum ADAMTS3.

Plasmonic nanopores combine nanofluidic confinement with electromagnetic field enhancement, enabling optical interrogation of single molecules in sub-wavel

In the food industry, innovative packaging solutions are increasingly important for reducing food waste and contributing to global sustainability efforts. However, current food packaging is generally passive and unable to adapt to changes in the food environment in real time. To address this, a battery‐less and autonomous smart packaging system is developed that wirelessly powers closed‐loop sensing and release of active compounds. This system integrates a gas sensor for real‐time food monitoring, a Near‐Field Communication (NFC) antenna, and a controlled release of active compounds to prevent quality deterioration in the complex food environment. The ability of the developed smart packaging system is demonstrated, to continuously monitor the freshness of fish products and to trigger the release of active compounds when the food starts to spoil. The system is able to extend the shelf‐life of the food product up to 14 days, due to the controlled release of antioxidant and antibacterial compounds. The system can pave the way toward an Internet of Things solution that addresses protection, active prevention of food spoilage, and sustainability, facing all the current challenges of the food packaging industry.

Solid-state nanopores are a key platform for single-molecule detection and analysis that allow engineering of their properties by controlling size, shape, and chemical functionalization. However, approaches relying on polymers have limits for what concerns hardness, robustness, durability, and refractive index. Nanopores made of oxides with high dielectric constant would overcome such limits and have the potential to extend the suitability of solid-state nanopores toward optoelectronic technologies. Here, we present a versatile method to fabricate three-dimensional nanopores made of different dielectric oxides with convex, straight, and concave shapes and demonstrate their functionality in a series of technologies and applications such as ionic nanochannels, ionic current rectification, memristors, and DNA sensing. Our experimental data are supported by numerical simulations that showcase the effect of different shapes and oxide materials. This approach toward robust and tunable solid-state nanopores can be extended to other 3D shapes and a variety of dielectrics.

Solid-state nanopore gating inspired by biological ion channels is gaining increasing traction due to a large range of applications in biosensing and drug delivery. Integration of stimuli-responsive molecules such as poly(N-isopropylacrylamide) (PNIPAM) inside nanopores can enable temperature-dependent gating, which so far has only been demonstrated using external heaters. In this work, we combine plasmonic resonators inside the nanopore architecture with PNIPAM to enable optical gating of individual or multiple nanopores with micrometer resolution and a switching speed of few milliseconds by thermo-plasmonics. We achieve a temperature change of 40 kelvin per millisecond and demonstrate the efficacy of this method using nanopore ionic conductivity measurements that enables selective activation of individual nanopores in an array. Moreover, the selective gating of specific nanopores in an array can set distinct ionic conductance levels: low, medium, and high (i.e., 0, 1, and 2), which could be exploited for logical gating with optical signal control. Such selective optical gating in nanopore arrays marks a breakthrough in nanofluidics, as it paves the way towards smart devices that offer multifunctional applications including biosensing, targeted drug delivery, and fluidic mixing.

Aptamers that undergo conformational changes upon small-molecule recognition have been shown to gate the ionic flux through nanopores by rearranging the charge density within the aptamer-occluded orifice. However, mechanistic insight into such systems where biomolecular interactions are confined in nanoscale spaces is limited. To understand the fundamental mechanisms that facilitate the detection of small-molecule analytes inside structure-switching aptamer-modified nanopores, we correlated experimental observations to theoretical models. We developed a dopamine aptamer-functionalized nanopore sensor with femtomolar detection limits and compared the sensing behavior with that of a serotonin sensor fabricated with the same methodology. When these two neurotransmitters with comparable mass and equal charge were detected, the sensors showed an opposite electronic behavior. This distinctive phenomenon was extensively studied using complementary experimental techniques such as quartz crystal microbalance with dissipation monitoring, in combination with theoretical assessment by the finite element method and molecular dynamic simulations. Taken together, our studies demonstrate that the sensing behavior of aptamer-modified nanopores in detecting specific small-molecule analytes correlates with the structure-switching mechanisms of individual aptamers. We believe that such investigations not only improve our understanding of the complex interactions occurring in confined nanoscale environments but will also drive further innovations in biomimetic nanopore technologies.

Triboelectric nanogenerators (TENGs) have demonstrated great promise especially for the realization of self‐powered biomedical sensors. Nevertheless, developing TENG sensors able to detect the broad range of biomechanical movements experienced on the human body is still a challenge. Herein, a unique ridge‐structured device sensitive to wide range of forces is reported (i.e., low‐forced pulse monitoring to high‐forced gait monitoring). The device is composed of thermoplastic polyurethane layer sandwiched between two textured silicon elastomeric layers. Compared to non‐textured surface configurations, the proposed ridged‐structure provides an increased frictional contact area between the triboelectric materials, while also acting as a spacer between the triboelectric materials. The influence of ridge dimensions on the output performance is investigated by mechanical simulations and electromechanical experimental tests. The optimized device shows a maximum peak output power and current densities of 490 mW m⁻² and 1750 µA m⁻², respectively at 30 N and 7 Hz of compressive forces. The proposed device exhibits stable electrical output for 10000 cycles. As a proof of concept, the proposed device is used as wearable sensors for monitoring pulse rate, breath patterns, and gait movements. The study suggests the possibility of utilization of novel‐structured sandwich‐type elastomer ridge‐based TENG in different aspects of biomedical sensing and smart wearable application.

Plasmonic solid‐state nanopores with tunable hole diameters can be prepared via a photocatalytic effect resulting from the enhanced electromagnetic (EM) field inside a metallic ring on top of a dielectric nanotube. Under white light illumination, the plasmon‐enhanced EM‐field induces a site‐selective metal nucleation and growth within the ring. This approach is used to prepare Au and bimetallic Au–Ag nano‐rings and demonstrate the reduction of the initial inner diameter of the nanopore down to 4 nm. The tunability of the nanopore diameter can be used to enable optimized detection of single entities with different sizes. As a proof‐of‐concept, single object detection of double stranded DNA (dsDNA) and Au nanoparticles (AuNPs) with a diameter down to 15 nm is performed. Numerical simulations provide insights into the EM‐field distribution and confinement, showing that a field intensity enhancement of up to 10⁴ can be achieved inside the nanopores. This localized EM‐field can be used to perform enhanced optical measurements and generate local heating, thereby modifying the properties of the nanopore. Such a flexible approach also represents a valuable tool to investigate plasmon‐driven photochemical reactions, and it can represent an important step toward the realization of new plasmonic devices.

CNTs based chemiresistive gas sensors are known to not fully recover to the baseline after gas exposure. This is why often heat is applied to thermally activate the sensor and improve the gas desorption process occur- ring at the surface. In this paper, we combine single-walled CNTs (SWCNTs) with conjugated polymers (CPs) i.e., Poly(3-hexylthiophene)(P3HT), to realize chemiresistive gas sensors with improved recovery. Five configurations were fabricated with diverse positions of the sensing material layers with respect to the interdigitated electrodes (IDEs), namely: SWCNTs/IDEs and P3HT/IDEs as controls for the CNTs and P3HT singular materials; SWCNTs/P3HT/IDEs, SWCNTs/IDEs/P3HT and P3HT/SWCNTs/IDEs as combined sensing materials layers configurations. The results show that in particular, the P3HT/SWCNTs/IDEs sensors exhibit better performance with respect to the other configurations when exposed to 5, 25, and 50 ppm NH3. Improvements in terms of response time (103 seconds faster at 5 ppm), sensor response (+26.83% at 50 ppm), and improved recovery to the baseline (+25.69% and +11.34% at 5 and 50 ppm respectively) were obtained when evaluated against SWCNTs/IDEs sensors. These findings suggest that addition of CPs (i.e. P3HT) may be a promising approach to enhance the performance and stability of SWCNTs-based chemiresistive gas sensors, providing a new direction for future research in this field. Future research to investigate the effect of others CPs on the CNTs based chemiresistive gas sensors will be needed to realize more efficient and reliable ammonia gas sensors.

Aptamers are chemically synthesized single-stranded DNA or RNA oligonucleotides widely used nowadays in sensors and nanoscale devices as highly sensitive biorecognition elements. With proper design, aptamers are able to bind to a specific target molecule with high selectivity. To date, the systematic evolution of ligands by exponential enrichment (SELEX) process is employed to isolate aptamers. Nevertheless, this method requires complex and time-consuming procedures. In silico methods comprising machine learning models have been recently proposed to reduce the time and cost of aptamer design. In this work, we present a new in silico approach allowing the generation of highly sensitive and selective RNA aptamers towards a specific target, here represented by ammonium dissolved in water. By using machine learning and bioinformatics tools, a rational design of aptamers is demonstrated. This “smart” SELEX method is experimentally proved by choosing the best five aptamer candidates obtained from the design process and applying them as functional elements in an electrochemical sensor to detect, as the target molecule, ammonium at different concentrations. We observed that the use of five different aptamers leads to a significant difference in the sensor’s response. This can be explained by considering the aptamers’ conformational change due to their interaction with the target molecule. We studied these conformational changes using a molecular dynamics simulation and suggested a possible explanation of the experimental observations. Finally, electrochemical measurements exposing the same sensors to different molecules were used to confirm the high selectivity of the designed aptamers. The proposed in silico SELEX approach can potentially reduce the cost and the time needed to identify the aptamers and potentially be applied to any target molecule.