Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs

Abstract Accurate affinity assessments play an important role in drug discovery, screening, and efficacy evaluation. Label‐free affinity biosensors are recognized as a dependable and standard technology for addressing this challenge. This study constructs a free electron density gradient‐enhanced me...

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Main Authors: Youqian Chen, Hongli Fan, Rui Li, Huazhi Zhang, Rui Zhou, Gang L. Liu, Chunmeng Sun, Liping Huang
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202404559
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author Youqian Chen
Hongli Fan
Rui Li
Huazhi Zhang
Rui Zhou
Gang L. Liu
Chunmeng Sun
Liping Huang
author_facet Youqian Chen
Hongli Fan
Rui Li
Huazhi Zhang
Rui Zhou
Gang L. Liu
Chunmeng Sun
Liping Huang
author_sort Youqian Chen
collection DOAJ
description Abstract Accurate affinity assessments play an important role in drug discovery, screening, and efficacy evaluation. Label‐free affinity biosensors are recognized as a dependable and standard technology for addressing this challenge. This study constructs a free electron density gradient‐enhanced meta‐surface plasmon resonance (FED‐MSPR) biosensor through a finite‐difference time‐domain simulation model, the biosensor demonstrates superior detection performance in accurately determining affinity and kinetic rate constants. By controlling the dielectric properties of the metal on the surface of the nanocup arrays, the plasmon resonance effects are easily tuned without changing the nanostructure design. Compared with the single‐layer gold chip, the triple‐layer FED‐MSPR chip demonstrated a four‐fold improvement in resolution at the optimal resonance peak. Additionally, the sensitivity and figure of merit (FOM) of the multi‐layer chip increased by 3.5 and 7.99 times, respectively. Following modification with high‐ and low‐staggered carboxylation, the noise‐signal ratio and baseline stability of the real‐time kinetic curves based on these chips are significantly enhanced. The developed carboxylation FED‐MSPR platform is successfully used to perform affinity assays for Adalimumab and TNF‐α protein, resulting in favorable dynamic curves. These findings validate the proposed FED‐MSPR biosensor platform as cost‐effective, rapid, sensitive, and label‐free, facilitating real‐time quality control in drug development.
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spelling doaj-art-07efa0d4f01a432cbe0f8ba621bcc2f72024-12-11T16:00:49ZengWileyAdvanced Science2198-38442024-12-011146n/an/a10.1002/advs.202404559Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy DrugsYouqian Chen0Hongli Fan1Rui Li2Huazhi Zhang3Rui Zhou4Gang L. Liu5Chunmeng Sun6Liping Huang7College of Life Science and Technology Huazhong University of Science and Technology 1037 Luo Yu Road Wuhan 430074 P. R. ChinaCollege of Life Science and Technology Huazhong University of Science and Technology 1037 Luo Yu Road Wuhan 430074 P. R. ChinaCollege of Life Science and Technology Huazhong University of Science and Technology 1037 Luo Yu Road Wuhan 430074 P. R. ChinaBiosensor R&D Department Liangzhun (Wuhan) Life Technology Co. Ltd Wuhan 430070 P. R. ChinaBiosensor R&D Department Liangzhun (Wuhan) Life Technology Co. Ltd Wuhan 430070 P. R. ChinaCollege of Life Science and Technology Huazhong University of Science and Technology 1037 Luo Yu Road Wuhan 430074 P. R. ChinaDepartment of Pharmaceutics School of Pharmacy China Pharmaceutical University 639 Longmian Avenue Nanjing 211198 P. R. ChinaCollege of Life Science and Technology Huazhong University of Science and Technology 1037 Luo Yu Road Wuhan 430074 P. R. ChinaAbstract Accurate affinity assessments play an important role in drug discovery, screening, and efficacy evaluation. Label‐free affinity biosensors are recognized as a dependable and standard technology for addressing this challenge. This study constructs a free electron density gradient‐enhanced meta‐surface plasmon resonance (FED‐MSPR) biosensor through a finite‐difference time‐domain simulation model, the biosensor demonstrates superior detection performance in accurately determining affinity and kinetic rate constants. By controlling the dielectric properties of the metal on the surface of the nanocup arrays, the plasmon resonance effects are easily tuned without changing the nanostructure design. Compared with the single‐layer gold chip, the triple‐layer FED‐MSPR chip demonstrated a four‐fold improvement in resolution at the optimal resonance peak. Additionally, the sensitivity and figure of merit (FOM) of the multi‐layer chip increased by 3.5 and 7.99 times, respectively. Following modification with high‐ and low‐staggered carboxylation, the noise‐signal ratio and baseline stability of the real‐time kinetic curves based on these chips are significantly enhanced. The developed carboxylation FED‐MSPR platform is successfully used to perform affinity assays for Adalimumab and TNF‐α protein, resulting in favorable dynamic curves. These findings validate the proposed FED‐MSPR biosensor platform as cost‐effective, rapid, sensitive, and label‐free, facilitating real‐time quality control in drug development.https://doi.org/10.1002/advs.202404559affinityfree electron densityimmunotherapy drugslabel‐free detectionMetaSPRmolecular interactions
spellingShingle Youqian Chen
Hongli Fan
Rui Li
Huazhi Zhang
Rui Zhou
Gang L. Liu
Chunmeng Sun
Liping Huang
Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs
Advanced Science
affinity
free electron density
immunotherapy drugs
label‐free detection
MetaSPR
molecular interactions
title Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs
title_full Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs
title_fullStr Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs
title_full_unstemmed Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs
title_short Free Electron Density Gradients Enhanced Biosensor for Ultrasensitive and Accurate Affinity Assessment of the Immunotherapy Drugs
title_sort free electron density gradients enhanced biosensor for ultrasensitive and accurate affinity assessment of the immunotherapy drugs
topic affinity
free electron density
immunotherapy drugs
label‐free detection
MetaSPR
molecular interactions
url https://doi.org/10.1002/advs.202404559
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