A highly sensitive electrochemical biosensor with a signal amplification platform of electrodeposited gold nanoparticle (AuNP) has been developed and characterized. The sizes of the synthesized AuNP were found to be critical for the performance of biosensor in which the sizes were dependent on HAuCl₄ and acid concentrations; as well as on scan cycles and scan rates in the gold electro-reduction step. Systematic investigations of the adsorption of proteins with different sizes from aqueous electrolyte solution onto the electrodeposited AuNP surface were performed with a potentiometric method and calibrated by design of experiment (DOE). The resulting amperometric glucose biosensors was demonstrated to have a low detection limit (>50 μM) and a wide linear range after optimization with AuNP electrodeposition.

Since the discovery of polytetrafluoroethylene (PTFE) in 1938, fluorinated polymers have drawn attention in the chemical and pharmaceutical field, as well as in optical and microelectronics applications. The reasons for this attention are their high thermal and oxidative stability, excellent chemical resistance, superior electrical insulating ability, and optical transmission properties. Despite their unprecedented combination of desirable attributes, PTFE and copolymers of tetrafluoroethylene (TFE) with hexafluoropropylene and perfluoropropylvinylether are crystalline and exhibit poor solubility in solvents, which makes their processability very challenging. Since the 1980s, several classes of solvent-soluble amorphous perfluorinated polymers showing even better optical and gas transport properties were developed and commercialized. Amorphous perfluoropolymers exhibit, however, moderate selectivity in gas and liquid separations. Recently, we have synthesized various new perfluorodioxolane polymers which are amorphous, soluble, chemically and thermally stable, while exhibiting much enhanced selectivity. In this article, we review state-of-the-art and recent progress in these perfluorodioxolane polymers for gas separation membrane applications.

Dysregulated inflammatory responses are characterized by inappropriate levels of inflammatory markers, speed of generation, degree, and major site of production, such as a vital organ. COVID-19 severity and mortality are strongly associated with interleukin (IL)-6 levels. High IL-6 levels are also observed in idiopathic Multicentric Castleman Disease (iMCD). Previously, we developed the first anti-IL-6 monoclonal antibody (mAb) treatments and showed that C-reactive protein (CRP) production could be fully controlled by IL-6 in humans. Using mathematical modeling, with CRP as an IL-6 surrogate marker, we predicted the ability of an anti-IL-6 mAb to block plasma IL-6 activity and showed IL-6 inhibition was dependent on the extent of whole-body IL-6 production. We postulate that in patients (pts) in whom IL-6 concentration at the site of inflammation is higher than in the plasma, full blockade of plasma IL-6 activity, shown by complete CRP inhibition, is the minimum requirement to achieve clinical efficacy. CRP inhibition with tocilizumab (TCZ) in pts with COVID-19. We identified 35 published studies evaluating the efficacy or potential role of anti-IL-6 therapy in pts with severe COVID-19. Surprisingly, only one (Luo et al. J Med Virol 2020;92:814) reported dynamics of CRP reduction for individual patients throughout treatment. We fitted a hypothetical curve of CRP reduction required to completely block IL-6, based on the half-life of CRP, and added data points of CRP serum levels from pts treated with anti-IL-6 receptor (IL-6R) therapy, TCZ, in this study. Complete reduction of CRP was not achieved in all patients: 3 pts who died had CRP levels ≥12.8 mg/l. Of 2 pts whose disease worsened, CRP levels were 93.5 mg/l and 6.3 mg/l. However, pts whose condition stabilized (n=9), or whose symptoms improved (n=1), had CRP levels close to the theoretical curve that is likely required to fully block IL-6 (CRP levels ≤5.0 mg/l). Half of these pts had been given repeated doses of TCZ. Siltuximab (SIL) treatment (NCT01024036 trial) for pts with iMCD. To assess the impact of baseline CRP levels on response to anti-IL-6 therapy, SIL, patients were divided into low and high CRP groups based on a baseline CRP level threshold of 40 mg/l (corresponding to ~40 pg/ml of IL-6; Fig 1). In patients with low baseline CRP levels (40 mg/l; n=17), CRP levels were significantly reduced on day 8 (n=17; P<0.0001) and day 15 (n=15; P<0.0001) post-dosing (Fig 1). A significant increase in CRP levels from day 8 to day 15 was observed in these patients (P=0.0120); this increase was not observed in patients with low baseline CRP levels (P=0.243; Fig 1). There was a negative correlation between maximum CRP and hemoglobin change (P<0.001). Inhibition of IL-6 activity by anti-IL-6 (SIL 700 mg) and anti-IL-6R (TCZ 800 mg) as monotherapy, intensified, or combined therapy. To evaluate the effect of therapy on IL-6 activity, our algorithm modeled inhibition of IL-6-(IL-6R/soluble IL-6R)-gp130 transducer complexes. This serves as a proxy for IL-6 bioactivity and accounts for the buffering capacity of gp130, which can be overwhelmed in inflammatory situations with high IL-6 concentrations. Due to uncertainty over the concentration of mAbs in alveoli relative to plasma, we modeled the effects of SIL and TCZ at local concentrations of 100%, 10%, and 1% (Fig 2) of those in plasma. Our model demonstrated that anti-IL-6 was associated with stronger inhibition of CRP than anti-IL-6R. However, only the association of both anti-IL-6 and anti-IL-6R mAbs was associated with a total blockade of CRP, which is probably necessary when IL-6 levels are associated with high risk to the patient. Different administration schedules to intensify anti-IL-6 therapy were modeled, including the repeated or combined use of anti-IL-6 and anti-IL-6R mAbs. The results form a basis to optimize treatment strategies to avoid the cytokine storm in several diseases, including cancer, iMCD, and autoimmune disorders. The feasibility of the theoretically defined approaches needs to be evaluated, particularly the potential side-effect profile for a combined treatment approach. In conclusion, in clinical practice, IL-6 inhibition should be individualized based on pathophysiology and regular CRP monitoring.

The ability of different crosslinkers to crosslink nanometer thick films of the polymer poly(mercaptopropyl)methylsiloxane (PMPMS), thus stabilizing these films on solid supports, was investigated. The four crosslinkers included 1,11-bismaleimidotriethyleneglycol (BM(PEG)₃), tris-(2-maleimidoethyl)amine (TMEA), bismaleimidohexane (BMH), and 1,1′-(methylenedi-4,1-phenylene) bismaleimide (BMDPM). PMPMS films treated with the four crosslinkers were compared in the effectiveness of achieved crosslinking, continuity and stability of the films to rearrangement at elevated temperatures, and modification with single-stranded DNA. The results of electrochemical analyses show that more hydrophilic crosslinkers had difficulty reacting fully with PMPMS thiols, even in these nanometer thin layers. This observation highlights the critical importance of selecting crosslinkers that are chemically compatible. Optimal selection of crosslinker yielded films in which the polymer film was largely incapable of rearranging, even at elevated temperatures, yielding reproducible and stable layers. These results validate use of these supports for applications such as monitoring thermal denaturation of immobilized DNA duplexes.