Microfluidic thread-based analytical devices for point-of-care detection of therapeutic antibody in blood

Riho Shimazu, Kosuke Tomimuro, Yan Ni, Cristina Malegori, Vahid Hamedpour, Yuki Hiruta, Paolo Oliveri, Maarten Merkx, Daniel Citterio

研究成果: Article査読

抄録

In therapies involving therapeutic antibodies, therapeutic drug monitoring (TDM) has the potential to substantially increase clinical efficacy and to enable more economical drug use, because the clearance from the bloodstream after administration is patient dependent. Since TDM must be performed continuously and over extended time periods, it should ideally be achieved through an economical and easy to perform point-of-care (POC) assay. Here, we introduce a new analytical method for POC TDM of the clinically important therapeutic antibody cetuximab, using microfluidic thread-based analytical devices (µTADs) as a platform for a bioluminescence resonance energy-transfer (BRET) switching sensor protein for simple quantitative antibody detection. The µTAD is pre-treated with NaCl for blood plasma separation and a BRET switching sensor protein and its substrate for cetuximab detection, integrating all elements required for a reagent-free, single-step assay. A change in bioluminescence emission color depending on cetuximab concentrations occurs after whole blood application. The device design enables the quantification of cetuximab within the therapeutically relevant blood concentration range in 2.5 min using only 2 µL of whole blood. The results obtained are independent of the blood volume. This µTAD can be stored for about one month at − 20 °C, a temperature compatible with commonly available freezers. The application of mathematical morphology recognition (MMR)-integrated image processing techniques for the automatic selection of regions of interest (ROIs) yields results with minimal error. The simplicity of use, rapidity, and cost-effectiveness of this µTAD are expected to offer the possibility of achieving TDM of therapeutic antibodies at POC for individual patients.

本文言語English
論文番号131002
ジャーナルSensors and Actuators B: Chemical
352
DOI
出版ステータスPublished - 2022 2月 1

ASJC Scopus subject areas

  • 電子材料、光学材料、および磁性材料
  • 器械工学
  • 凝縮系物理学
  • 表面、皮膜および薄膜
  • 金属および合金
  • 電子工学および電気工学
  • 材料化学

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