A Mesoporous Gold Sensor Unveils Phospho PD-L1 in Extracellular Vesicles as a Proxy for PD-L1 Expression in Lung Cancer Tissue.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy or fine needle aspiration that are currently used to identify patients most likely to respond to single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient tissue to generate a PD-L1 tissue proportion score (TPS) ≥ 50% using immunohistochemistry remains a challenge that potentially may be overcome by liquid biopsies. This study utilized a mesoporous gold sensor (MGS) assay to examine the phosphorylation status of PD-L1 in plasma extracellular vesicles (EV pPD-L1) and PD-L1 levels in plasma from NSCLC patient samples and their association with tumor PD-L1 TPS. The 3-dimensional mesoporous network of the electrodes provides a large surface area, high signal-to-noise ratio, and a superior electro-conductive framework, thereby significantly improving the detection sensitivity of PD-L1 nanosensing. Test (n = 20) (Pearson's r = 0.99) and validation (n = 45) (Pearson's r = 0.99) cohorts show that EV pPD-L1 status correlates linearly with the tumor PD-L1 TPS assessed by immunohistochemistry irrespective of the tumor stage, with 64% of patients overall showing detectable EV pPD-L1 levels in plasma. In contrast to the EV pPD-L1 results, plasma PD-L1 levels did not correlate with the tumor PD-L1 TPS score or EV pPD-L1 levels. These data demonstrate that EV pPD-L1 levels may be used to select patients for appropriate PD-1 and PD-L1 ICI therapy regimens in early, locally advanced, and advanced NSCLC and should be tested further in randomized controlled trials. Most importantly, the assay used has a less than 24h turnaround time, facilitating adoption of the test into the routine diagnostic evaluation of patients prior to 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).

Flexible Nanoarchitectonics for Biosensing and Physiological Monitoring Applications.

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm-2  µM-1 , which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications.

Magnetically controlled reversible shape-morphing microrobots with real-time X-ray imaging for stomach cancer applications.

Stomach cancer is a global health concern as millions of cases are reported each year. In the present study, we developed a pH-responsive microrobot with good biocompatibility, magnetic-field controlled movements, and the ability to be visualized via X-ray imaging. The microrobot consisted of composite resin and a pH-responsive layer. This microrobot was found to fold itself in high pH environments and unfold itself in low pH environments. In addition, the neodymium (NdFeB) magnetic nanoparticles present inside the composite resin provided the microrobot with an ability to be controlled by a magnetic field through an electromagnetic actuation system, and the monomeric triiodobenzoate-based particles were found to act as contrast agents for real-time X-ray imaging. The doxorubicin coating on the microrobot's surface resulted in a high cancer-cell killing effect. Finally, we demonstrated the proposed microrobot under an ex vivo environment using a pig's stomach. Thus, this approach can be a potential alternative to targeted drug carriers, especially for stomach cancer applications.

Mesoporous gold-silver alloy films towards amplification-free ultra-sensitive microRNA detection.

Herein, we report the preparation of mesoporous gold (Au)-silver (Ag) alloy films through the electrochemical micelle assembly process and their applications as microRNA (miRNA) sensors. Following electrochemical deposition and subsequent removal of the templates, the polymeric micelles can create uniformly sized mesoporous architectures with high surface areas. The resulting mesoporous Au-Ag alloy films show high current densities (electrocatalytic activities) towards the redox reaction between potassium ferrocyanide and potassium ferricyanide. Following magnetic isolation and purification, the target miRNA is adsorbed directly on the mesoporous Au-Ag film. Electrochemical detection is then enabled by differential pulse voltammetry (DPV) using the [Fe(CN)6]3-/4- redox system (the faradaic current for the miRNA-adsorbed Au-Ag film decreases compared to the bare film). The films demonstrate great advantages towards miRNA sensing platforms to enhance the detection limit down to attomolar levels of miR-21 (limit of detection (LOD) = 100 aM, s/n = 3). The developed enzymatic amplification-free miniaturized analytical sensor has promising potential for RNA-based diagnosis of diseases.

Designed Patterning of Mesoporous Metal Films Based on Electrochemical Micelle Assembly Combined with Lithographical Techniques.

Mesoporous noble metals and their patterning techniques for obtaining unique patterned structures are highly attractive for electrocatalysis, photocatalysis, and optoelectronics device applications owing to their expedient properties such as high level of exposed active locations, cascade electrocatalytic sites, and large surface area. However, patterning techniques for mesoporous substrates are still limited to metal oxide and silica films, although there is growing demand for developing techniques related to patterning mesoporous metals. In this study, the first demonstration of mesoporous metal films on patterned gold (Au) substrates, prefabricated using photolithographic techniques, is reported. First, different growth rates of mesoporous Au metal films on patterned Au substrates are demonstrated by varying deposition times and voltages. In addition, mesoporous Au films are also fabricated on various patterns of Au substrates including stripe and mesh lines. An alternative fabrication method using a photoresist insulating mask also yields growth of mesoporous Au within the patterning. Moreover, patterned mesoporous films of palladium (Pd) and palladium-copper alloy (PdCu) are demonstrated on the same types of substrates to show versatility of this method. Patterned mesoporous Au films (PMGFs) show higher electrochemically active surface area (ECSA) and higher sensitivity toward glucose oxidation than nonpatterned mesoporous Au films (NMGF).