Lateral flow assay modified with time-delay wax barriers as a sensitivity and signal enhancement strategy
BIOSENSORS & BIOELECTRONICS
Authors: Sena-Torralba, Amadeo; Duy Ba Ngo; Parolo, Claudio; Hu, Liming; Alvarez-Diduk, Ruslan; Francisco Bergua, Jose; Rosati, Giulio; Surareungchai, Werasak; Merkoci, Arben
Abstract
The ease of use, low cost and quick operation of lateral flow assays (LFA) have made them some of the most common point of care biosensors in a variety of fields. However, their generally low sensitivity has limited their use for more challenging applications, where the detection of low analytic concentrations is required. Here we propose the use of soluble wax barriers to selectively and temporarily accumulate the target and label nanoparticles on top of the test line (TL). This extended internal incubation step promotes the formation of the immune-complex, generating a 51.7-fold sensitivity enhancement, considering the limit of quantification, and up to 96% signal enhancement compared to the conventional LFA for Human IgG (H-IgG) detection.
Cetuximab Exhibits Sex Differences in Lymphatic Exposure after Intravenous Administration in Rats in the Absence of Differences in Plasma Exposure
PHARMACEUTICAL RESEARCH
Authors: Kuilamu, Esther; Subasic, Christopher; Cowin, Gary J.; Simpson, Fiona; Minchin, Rodney F.; Kaminskas, Lisa M.
Abstract
Purpose The aim of this work was to identify whether biochemical and physiological sources of mAb pharmacokinetic sex-effects could be identified in the rat model where target-mediated disposition is avoided. Methods Plasma and lymphatic pharmacokinetics of the humanised anti-EGFR antibody cetuximab, along with potential physiological and biochemical drivers of pharmacokinetic sex differences, were examined in male and female rats. Cetuximab was used as a model mAb since plasma clearance is slower in female patients. Results When plasma concentrations were normalised to dose, female rats displayed slower plasma clearance than males, but no significant differences were observed in liver and spleen biodistribution. Sex differences in apparent plasma clearance, however, were abolished after normalisation to body weight, surface area or fat-free mass. Significant sex differences were observed in plasma testosterone, endogenous IgG and fat free mass, but did not correlate with apparent clearance. Females did, however, show two-fold higher lymphatic exposure compared to males. Conclusions These data suggested that mAbs more efficiently access lymph in females, but this does not affect plasma pharmacokinetics or biodistribution. Further, the data suggest that sex differences observed in humans could be a function of antigen density.