Solid-phase extraction coupled to automated centrifugal microfluidics SERS: Improving quantification of therapeutic drugs in human serum.

Autor: Soufi G; Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; BioInnovation Institute Foundation, Copenhagen N, 2200, Denmark. Electronic address: gohsoo@dtu.dk., Badillo-Ramírez I; Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; BioInnovation Institute Foundation, Copenhagen N, 2200, Denmark., Serioli L; Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; BioInnovation Institute Foundation, Copenhagen N, 2200, Denmark., Altaf Raja R; Department of Paediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Copenhagen, 2100, Denmark., Schmiegelow K; Department of Paediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Copenhagen, 2100, Denmark., Zor K; Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; BioInnovation Institute Foundation, Copenhagen N, 2200, Denmark., Boisen A; Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; BioInnovation Institute Foundation, Copenhagen N, 2200, Denmark.
Jazyk: angličtina
Zdroj: Biosensors & bioelectronics [Biosens Bioelectron] 2024 Dec 15; Vol. 266, pp. 116725. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.bios.2024.116725
Abstrakt: Surface-enhanced Raman spectroscopy (SERS) is a powerful method in analytical chemistry, but its application in real-life medical settings has been limited due to technical challenges. In this work, we introduce an innovative approach that is meant to advance the automation of microfluidics SERS to improve reproducibility and label-free quantification of two widely used therapeutic drugs, methotrexate (MTX) and lamotrigine (LTG), in human serum. Our methodology involves a miniaturized solid-phase extraction (μ-SPE) method coupled to a centrifugal microfluidics disc with incorporated SERS substrates (CD-SERS). The CD-SERS platform enables simultaneous controlled sample wetting and accurate SERS mapping. Together with the assay we implemented a machine learning method based on Partial Least Squares Regression (PLSR) for robust data analysis and drug quantification. The results indicate that combining μ-SPE with CD-SERS (μ-SPE to CD-SERS) led to a substantial improvement in the signal-to-noise ratio compared to combining CD-SERS with ultrafiltration or protein precipitation. The PLSR model enabled us to obtain the limit of detection and quantification for MTX as 2.90 and 8.92 μM, respectively, and for LTG as 10.76 and 32.29 μM. We also validated our μ-SPE to CD-SERS method for MTX against HPLC and immunoassay (p-value <0.05), using patient samples undergoing MTX therapy. In addition, we achieved a satisfactory recovery rate (80%) for LTG when quantifying it in patient samples. Our results show the potential of this newly developed approach as a strategy for therapeutic drugs in point-of-care clinical settings and highlight the benefits of automating label-free SERS assays.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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