A novel versatile animal-free 3D tool for rapid low-cost assessment of immunodiagnostic microneedles

SENSORS AND ACTUATORS B-CHEMICAL

卷:296

Article

Totti, Stella¹  Ng, Keng Wooi^2,3  Dale, Lorraine³  Lian, Guoping^1,4  Chen, Tao¹  Velliou, Eirini G.¹ 

[1] Univ Surrey, Dept Chem & Proc Engn, Bioproc & Biochem Engn Grp BioProChem, Guildford GU2 7XH, Surrey, England

[2] Newcastle Univ, Fac Med Sci, Sch Pharm, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[3] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England

[4] Unilever R&D Colworth, Colworth Pk, Sherbrook MK44 1LQ, Bedforshire, England

关键词: Microneedles;    Diagnostic device;    Biomarker detection;    S100B;    Melanoma;    Three-dimensional in vitro model;   

DOI  :  10.1016/j.snb.2019.126652

来源: Elsevier

【 摘 要 】

Microneedle devices offer minimally invasive and rapid biomarker extraction from the skin. However, the lack of effective assessment tools for such microneedle devices can delay their development into useful clinical applications. Traditionally, the microneedle performance is evaluated i) in vivo, using animal models, ii) ex vivo, on excised human or animal skin or iii) in vitro, using homogenised solutions with the target antigen to model the interstitial fluid. In vivo and ex vivo models are considered the gold-standard approach for the evaluation of microneedle devices because of their structural composition, however they do exhibit limitations. More specifically, they have limited availability and they present batch-to-batch variations depending on the skin origin. Furthermore, their use rises ethical concerns regarding compliance with the globally accepted 3Rs principle of reducing the use of animals for research purposes. At the same time, in vitro models fail to accurately mimic the structure and the mechanical integrity of the skin tissue that surrounds the interstitial fluid. In this study, we introduce for the first time an animal-free, mechanically robust, 3D scaffold that has great potential as an accurate in vitro evaluation tool for immunodiagnostic microneedle devices. More specifically, we demonstrate, for the first time, successful extraction and detection of a melanoma biomarker (S100B) using immunodiagnostic microneedles in the 3D culture system. Melanoma cells (A375) were cultured and expanded for 35 days in the highly porous polymeric scaffold followed by in situ capture of S100B with the microneedle device. Scanning electron microscopy showed a close resemblance between the 3D scaffold and human skin in terms of internal structure and porosity. The microneedle device detected S100B in the scaffold (with a detection pattern similar to the positive controls), while the biomarker was not detected in the surrounding liquid supernatants. Our findings demonstrate the great potential of this animal-free 3D tool for rapid and low-cost evaluation of microneedle devices.

【 授权许可】

Free