**1. Introduction**

The definition of biomarkers has evolved over time, and a broader definition was suggested by the World Health Organization as "a biomarker is any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease" [1,2]. More specific definitions such as "a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease and can be tested to see how well the body responds to treatment for a disease or condition" [3], and "a characteristic that can be objectively measured and quantitatively evaluated as an indicator of a normal biological and pathological process, or pharmacological responses to a therapeutic intervention" [4] were coined by the US National Cancer Institute, and the US National Institutes of Health, respectively. Biomarkers can be biological, chemical, or physical, and are measurable parameters indicative of a specific biological state. The detection of biomarkers is crucial for the diagnosis and treatment of numerous diseases [5]. Biomarkers are classified broadly into imaging biomarkers and molecular biomarkers based on their characteristics. Imaging biomarkers are often used in combination with various imaging tools, whereas molecular biomarkers comprise RNA, DNA, and proteins [6]. Molecular biomarkers are easily quantifiable from biological samples and can complement clinical characteristics [7,8]. Another category, known as pharmacodynamic biomarkers, is applied in drug development during dose optimization studies [9]. Based on the application, biomarkers are classified into prognostic biomarkers, diagnostic biomarkers, predictive biomarkers, and monitoring biomarkers [10]. Prognostic biomarkers help to identify the risk of disease progression in the future [11]. Diagnostic biomarkers help physicians to identify a specific disease condition [12], and predictive biomarkers predict the responses related to therapeutic interventions [11], whereas

**Citation:** Koyappayil, A.; Yagati, A.K.; Lee, M.-H. Recent Trends in Metal Nanoparticles Decorated 2D Materials for Electrochemical Biomarker Detection. *Biosensors* **2023**, *13*, 91. https://doi.org/10.3390/ bios13010091

Received: 7 November 2022 Revised: 27 December 2022 Accepted: 1 January 2023 Published: 5 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

a monitoring biomarker is usually measured for assessing the status of a medical condition or disease [13].

An ideal biomarker sensor must capture the biomarker selectively from the complex biological matrix of interfering molecules. Although nonspecific binding is still a concern, electrochemical detection methods, specifically electrochemical impedance spectroscopy (EIS), allow the selective analysis of biomarker detections by the resistive and/or capacitive changes due to physical and/or biomolecular interactions of the electrode surfaces coated with nanomaterials, DNA, proteins, etc. [14–16]. It is one of the basic and widely used approaches to determine the fundamental redox events at the electrode-electrolyte interface. However, evaluations are made by comparing the results of the EIS with cyclic voltammetry (CV) measurements. Also, differential pulse voltammetry (DPV) and square wave voltammetry (SWV) techniques are used in biomarker detection systems for both label and label-free approaches [17,18]. Among these techniques, CV-based detection sensing is widely reported due to its ability to explain the electrochemical events, such as oxidationreduction reactions and electron-transfer kinetics occurring at the electrode-electrolyte interface, and the mass transport towards the electrode surface [19–21]. The search for advanced functional materials for electrochemical biomarker detection has sparked a research interest in layered 2D materials over the past few years and several novel approaches were reported for the synthesis of various 2D materials and their nanocomposites with exciting immunosensor applications. The interest and demand for 2D materials have increased significantly, and the global market for 2D materials is expected to grow rapidly with a CAGR of 3.9% between 2020 and 2027 and a corresponding increase in valuation from 2.27 billion to 2.86 billion USD [22]. In this context, this review discusses the recent advances and challenges of metal nanoparticle decorated 2D materials for biomarker detection.
