An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use.

[68Ga]Ga-FAPI-46 is a promising new tracer for the imaging of fibroblast activation protein (FAP) by positron emission tomography (PET). Labeled FAP inhibitors (FAPIs) have demonstrated uptake in various types of cancers, including breast, lung, prostate, pancreatic and colorectal cancer. FAPI-PET also possesses a practical advantage over FDG-PET as fasting and resting are not required. [68Ga]Ga-FAPI-46 exhibits enhanced pharmacokinetic properties, improved tumor retention, and higher contrast images than the earlier presented [68Ga]Ga-FAPI-02 and [68Ga]Ga-FAPI-04. Although a manual synthesis protocol for [68Ga]Ga-FAPI-46 was initially described, in recent years, automated methods using different commercial synthesizers have been reported. In this work, we describe the development of the automated synthesis of [68Ga]Ga-FAPI-46 using the iPHASE MultiSyn synthesizer for clinical applications. Initially, optimization of the reaction time and comparison of the performance of four different solid phase extraction (SPE) cartridges for final product purification were investigated. Then, the development and validation of the production of 0.6-1.7 GBq of [68Ga]Ga-FAPI-46 were conducted using these optimized parameters. The product was synthesized in 89.8 ± 4.8% decay corrected yield (n = 6) over 25 min. The final product met all recommended quality control specifications and was stable up to 3 h post synthesis.

Development of a high-performance liquid chromatography method for rapid radiochemical purity measurement of [18 F]PSMA-1007, a PET radiopharmaceutical for detection of prostate cancer.

Since first becoming commercially available in 2018, the PET radiopharmaceutical [18 F]PSMA-1007 has been used widely for the diagnosis and staging of prostate cancer. A pharmacopoeia monograph first became available in 2021, prescribing a radiochemical purity specification of >91%, based on analytical results from both TLC (for [18 F]fluoride impurity alone) and HPLC (for all other 18 F-impurities). Though this monograph has provided clarity for the quality control testing of [18 F]PSMA-1007, it prescribes a HPLC method using phosphate buffer mobile phase that may present a risk of precipitation of phosphate salts in the HPLC system. The method also requires specialised hardware not immediately available to all laboratories. This work describes the development of a simple, rapid reversed-phase HPLC method utilising 0.1 M ammonium formate mobile phase for the accurate assessment of both [18 F]fluoride impurity and overall radiochemical purity in a single test. This method is especially useful for assessment of product stability over time. A more accurate TLC method for [18 F]fluoride impurity is also described.

Compressively Stressed Silicon Nanoclusters as an Antifracture Mechanism for High-Performance Lithium-Ion Battery Anodes.

Silicon has been considered a good candidate for replacing the commonly used carbon anodes for lithium-ion batteries (LIBs) due to its high specific capacity, which can be up to 11 times higher than that of carbon. However, the desirable advantage that silicon brings to battery performance is currently overshadowed by its stress-induced performance loss and high electronic resistivity. The induced stress arises from two sources, namely, the deposition process (i.e., residual stress) during fabrication and the volume expansion (i.e., mechanical stress) associated with the lithiation/delithiation process. Of the two, residual stress has largely been ignored, underestimated, or considered to have a negligible effect without any rigorous evidence being put forward. In this contribution, we produced silicon thin films having a wide range of residual stress and resistivity using a physical vapor deposition technique, magnetron sputtering. Three pairs of silicon thin-film anodes were utilized to study the effect of residual stress on the electrochemical and cyclability performance as anodes for LIBs. Each set consisted of a pair of films having essentially the same resistivity, density, thickness, and oxidation amount but distinctly different residual stresses. The comparison was evaluated by conducting charge/discharge cycling and cyclic voltammetry (CV) experiments. In contrast to the fixed belief within the literature, higher compressive residual-stress films showed better electrochemical and cycle performance compared to lower residual-stress films. The results, herein, present an informed understanding of the role that residual stress plays, which will help researchers improve the development of silicon-based thin-film anodes.

Secondary Structural Changes in Proteins as a Result of Electroadsorption at Aqueous-Organogel Interfaces.

The electroadsorption of proteins at aqueous-organic interfaces offers the possibility to examine protein structural rearrangements upon interaction with lipophilic phases, without modifying the bulk protein or relying on a solid support. The aqueous-organic interface has already provided a simple means of electrochemical protein detection, often involving adsorption and ion complexation; however, little is yet known about the protein structure at these electrified interfaces. This work focuses on the interaction between proteins and an electrified aqueous-organic interface via controlled protein electroadsorption. Four proteins known to be electroactive at such interfaces were studied: lysozyme, myoglobin, cytochrome c, and hemoglobin. Following controlled protein electroadsorption onto the interface, ex situ structural characterization of the proteins by FTIR spectroscopy was undertaken, focusing on secondary structural traits within the amide I band. The structural variations observed included unfolding to form aggregated antiparallel ß-sheets, where the rearrangement was specifically dependent on the interaction with the organic phase. This was supported by MALDI ToF MS measurements, which showed the formation of protein-anion complexes for three of these proteins, and molecular dynamic simulations, which modeled the structure of lysozyme at an aqueous-organic interface. On the basis of these findings, the modulation of protein secondary structure by interfacial electrochemistry opens up unique prospects to selectively modify proteins.

Electrochemical behaviour at a liquid-organogel microinterface array of fucoidan extracted from algae.

Fucoidans are sulfated polysaccharides mostly derived from algae and used in a number of applications (e.g. nutrition, cosmetics, pharmaceuticals and biomaterials). In this study, the electrochemical behaviour of fucoidans extracted from two algal species (Undaria pinnatifida and Fucus vesiculosus) was assessed using voltammetry at an array of micro-interfaces formed between two immiscible electrolyte solutions (µITIES) in which the organic electrolyte phase was gelled. Cyclic voltammetry revealed an adsorption process when scanning to negative potentials, followed by a desorption peak at ca. -0.50 V on the reverse scan, indicating the electroactivity of both fucoidans. U. pinnatifida fucoidan showed a more intense voltammetric signal compared to F. vesiculosus fucoidan. In addition, use of tridodecylmethylammonium (TDMA+) or tetradodecylammonium (TDDA+) as the organic phase electrolyte cation provided improved detection of both fucoidans relative to the use of bis(triphenylphosphoranylidene)ammonium (BTPPA+) cation. Application of adsorptive stripping voltammetry provided a linear response of current with fucoidan concentration in the range 2-20 µg mL-1 for U. pinnatifida fucoidan (with TDMA+) and 10-100 µg mL-1 for F. vesiculosus fucoidan (with TDDA+). The combination of TDMA+ in the organic phase and adsorptive pre-concentration for 180 s afforded a detection limit of 1.8 µg mL-1 fucoidan (U. pinnatifida) in aqueous phase of 10 mM NaOH and 2.3 µg mL-1 in synthetic urine (pH adjusted). These investigations demonstrate the electroactivity of fucoidans at the µITIES array and provide scope for their detection at low µg mL-1 concentrations using this approach.

An Electrochemical Sensing Platform Based on Liquid-Liquid Microinterface Arrays Formed in Laser-Ablated Glass Membranes.

Arrays of microscale interfaces between two immiscible electrolyte solutions (µITIES) were formed using glass membranes perforated with microscale pores by laser ablation. Square arrays of 100 micropores in 130 µm thick borosilicate glass coverslips were functionalized with trichloro(1H,1H,2H,2H-perfluorooctyl)silane on one side, to render the surface hydrophobic and support the formation of aqueous-organic liquid-liquid microinterfaces. The pores show a conical shape, with larger radii at the laser entry side (26.5 µm) than at the laser exit side (11.5 µm). The modified surfaces were characterized by contact angle measurements and X-ray photoelectron spectroscopy. The organic phase was placed on the hydrophobic side of the membrane, enabling the array of µITIES to be located at either the wider or narrower pore mouth. The electrochemical behavior of the µITIES arrays were investigated by tetrapropylammonium ion transfer across water-1,6-dichlorohexane interfaces together with finite element computational simulations. The data suggest that the smallest microinterfaces (formed on the laser exit side) were located at the mouth of the pore in hemispherical geometry, while the larger microinterfaces (formed on the laser entry side) were flatter in shape but exhibited more instability due to the significant roughness of the glass around the pore mouths. The glass membrane-supported µITIES arrays presented here provide a new platform for chemical and biochemical sensing systems.

Investigation of a solvent-cast organogel to form a liquid-gel microinterface array for electrochemical detection of lysozyme.

Ion transfer at aqueous-organogel interfaces enables the non-redox detection of ions and ionisable species by voltammetry. In this study, a non-thermal method for preparation of an organogel was employed and used for the detection of hen-egg-white-lysozyme (HEWL) via adsorptive stripping voltammetry at an array of aqueous-organogel microinterfaces. Tetrahydrofuran solvent casting was employed to prepare the organogel mixture, hence removing the need for heating of the solution to be gelled, as used in previous studies. Cyclic voltammetry of HEWL at the microinterface array revealed a broad adsorption process on the forward scan, at positive applied potentials, followed by a desorption peak at ca. 0.68 V, indicating the detection of HEWL in this region. Application of an adsorption step, where a constant optimized potential of 0.95 V was applied, followed by voltammetric detection provided for a linear response range of 0.02-0.84 µM and a detection limit of 0.030 µM for 300 s adsorption. The detection limit was further improved by utilizing differential pulse stripping voltammetry, resulting in detection limits of 0.017 µM, 0.014 µM, and 0.010 µM for adsorptive pre-concentration times of 60, 120 and 300 s, respectively, in unstirred solutions. These results are an improvement over other methods for the detection of HEWL at aqueous-organic interfaces and offers a basis for the label-free detection of protein.

Fingerprinting the tertiary structure of electroadsorbed lysozyme at soft interfaces by electrostatic spray ionization mass spectrometry.

Lysozyme can be electrochemically detected after adsorption at an electrified gel-water interface. Ex situ characterization by electrostatic spray ionization mass spectrometry provides insights into the interfacial detection mechanism by allowing changes to the tertiary structure of electroadsorbed lysozyme to be fingerprinted for the first time.

Stripping voltammetric detection of insulin at liquid-liquid microinterfaces in the presence of bovine albumin.

Electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) provides a platform for label-free detection of biomolecules. In this study, adsorptive stripping voltammetry (AdSV) was implemented at an array of microscale ITIES for the detection of the antidiabetic hormone insulin. By exploiting the potential-controlled adsorption of insulin at the ITIES, insulin was detected at 10 nM via subsequent voltammetric desorption. This is the lowest detected concentration reported to-date for a protein by electrochemistry at the ITIES. Surface coverage calculations indicate that between 0.1 and 1 monolayer of insulin forms at the interface over the 10-1000 nM concentration range of the hormone. In a step toward assessment of selectivity, the optimum adsorption potentials for insulin and albumin were determined to be 0.900 V and 0.975 V, respectively. When present in an aqueous mixture with albumin, insulin was detected by tuning the adsorption potential to 0.9 V, albeit with reduced sensitivity. This provides the first example of selective detection of one protein in the presence of another by exploiting optimal adsorption potentials. The results presented here provide a route to the improvement of detection limits and achievement of selectivity for protein detection by electrochemistry at the ITIES.

Detection of haemoglobin using an adsorption approach at a liquid-liquid microinterface array.

The behaviour of haemoglobin (Hb) at the interface between two immiscible electrolyte solutions (ITIES) has been examined for analytical purposes. When Hb is fully protonated under acidic conditions (pH

Behavior of lysozyme at the electrified water/room temperature ionic liquid interface.

Between the phases: The globular protein lysozyme was adsorbed and desorbed under electrochemical conditions at the water/room temperature ionic liquid microinterface array; the electrochemical desorption process provides a basis for protein detection at these interfaces.

Adsorptive stripping voltammetry of hen-egg-white-lysozyme via adsorption-desorption at an array of liquid-liquid microinterfaces.

Electrochemical adsorption and voltammetry of hen-egg-white-lysozyme (HEWL) was studied at an array of microinterfaces between two immiscible electrolyte solutions (µITIES). Adsorption of the protein was achieved at an optimal applied potential of 0.95 V, after which it was desorbed by a voltammetric scan to lower potentials. The voltammetric peak recorded during the desorption scan was dependent on the adsorption time and on the aqueous phase concentration of HEWL. The slow approach to saturation or equilibrium indicated that protein reorganization at the interface was the rate-determining step and not diffusion to the interface. For higher concentrations and longer adsorption times, a HEWL multilayer surface coverage of 550 pmol cm(-2) was formed, on the basis of the assumption that a single monolayer corresponded to a surface coverage of 13 pmol cm(-2). Implementation of adsorption followed by voltammetric detection as an adsorptive stripping voltammetric approach to HEWL detection demonstrated a linear dynamic range of 0.05-1 µM and a limit of detection of 0.03 µM, for 5 min preconcentration in unstirred solution; this is a more than 10-fold improvement over previous HEWL detection methods at the ITIES. These results provide the basis for a new analytical approach for label-free protein detection based on adsorptive stripping voltammetry.

Characterization of the electrochemical behavior of gastrointestinal fluids using a multielectrode sensor probe.

A characterization of gastrointestinal fluids has been performed by means of an electrochemical sensor that has potential for clinical in vivo and in vitro monitoring applications. The sensor comprised a three-electrode cell with a counter, reference, and four working electrodes, Au, Pt, Ir, and Rh. Cyclic voltammetry was used to obtain chemical information from faecal water (in vitro) and gut model (in vivo) fluids. Stable voltammetric responses were obtained for both fluids at these noble metal working electrodes. The responses differed in shape that demonstrated the discrimination capability and the potential for practical use as a tool for gastrointestinal fluid investigation. The analysis of the stability profiles in faecal water over a 14-h duration has indicated a possible adsorption mechanism with the formation of a biolayer on the sensor surface. The stability in gut model fluids over a 42-h duration has demonstrated a more stable profile, but the mechanisms involved are more complicated to determine.