Abstract

This review investigates optical sensor platforms for protein multiplexing, the ability to analyze multiple analytes simultaneously. Multiplexing is becoming increasingly important for clinical needs because disease and therapeutic response often involve the interplay between a variety of complex biological networks encompassing multiple, rather than single, proteins. Multiplexing is generally achieved through one of two routes, either through spatial separation on a surface (different wells or spots) or with the use of unique identifiers/labels (such as spectral separation—different colored dyes, or unique beads—size or color). The strengths and weaknesses of conventional platforms such as immunoassays and new platforms involving protein arrays and lab-on-a-chip technology, including commercially-available devices, are discussed. Three major public health concerns are identified whereby detecting medically-relevant markers using Point-of-Care (POC) multiplex assays could potentially allow for a more efficient diagnosis and treatment of diseases.

Highlights

  • Multiplexed Biomarker Detection for Clinical NeedsTechnological advances in fields such as genomics, proteomics and metabolomics have advanced our understanding of the underlying mechanisms of disease initiation, disease progression, and therapeutic response, and helped identify biomarkers useful in personalized medicine [1,2,3]

  • Typical assays such as an Enzyme-Linked Immunosorbent Assay (ELISA) allow single analyte detection, but multiplexed POC devices can be used to probe for many biomarkers simultaneously using one uniform testing method, thereby allowing for greater consistency in the data obtained for each analyte

  • Devices are key for the integration of all aspects of an assay onto one hand-held platform to create a true biosensor [26]. Device attributes such as Limit of Detection (LOD), specificity, sensitivity, reproducibility, reliability, robustness, cost, speed, and multiplexing capability are crucial in the design of a biosensor that can be used in a POC environment

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Summary

Introduction

Technological advances in fields such as genomics, proteomics and metabolomics have advanced our understanding of the underlying mechanisms of disease initiation, disease progression, and therapeutic response, and helped identify biomarkers useful in personalized medicine [1,2,3]. These biomarkers, such as proteins, can serve as diagnostic, prognostic, or therapeutic indicators and typically represent a surrogate endpoint used in addition to, or instead of, a clinical endpoint. (2) right diagnosis; (3) right treatment; (4) right drug/target; and (5) right dose/time Such a goal can only be realized through the combination of a clinical approach to medicine, completion of a comprehensive medical history, and utilization of data from appropriate testing such as in vitro diagnostic devices. IVDs for personalized medicine should be paired with a specific drug or drug combination that would be able to treat the patient safely and effectively with minimal adverse effects [11]

Significance of Multiplexed Protein Detection
Importance of Multiplexing for Clinical Use
Benefits of POC Biosensors in the Healthcare Field
Sensor Requirements for POC Use
Small Sample Volume
Detection System
Protein Detection
Conventional Optical Detection Methods for Multiplexed Protein Detection
Flow Cytometry
Fluorescence Immunoassays
Miniaturized Assays
Protein Microarrays
Lab-on-a-Chip Devices
Fiber Optic Methods
Current POC Sensors
Real-World Applicability
Acute Kidney Injury Biomarkers
Cardiac Biomarkers
Findings
Conclusions and Outlook
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