Progress and Outlook on Electrochemical Sensing of Lung Cancer Biomarkers

Abstract

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.

Keywords: impedance; microfluidics; multiplexing; nanocomposites; voltammetry.

Figure 2

(A) Amperometric immunosensor for the detection of CEA using ZnMn₂O₄@reduced graphene oxide composite [20]. (B) Potentiometrical electrochemical sensor for CEA detection [23]. (C) Dual-template rectangular nanotube molecularly imprinted polypyrrole for the impedimetric sensing of AFP and CEA [25].

Figure 7

(A) The selectivity of MXC-Fe₃O₄-Ru to CEA [87]. (B) Schematic representation of a paper-based microfluidic electrochemical immunodevice for CEA sensing [126].

Figure 1

Common biomarkers for SCLC diagnosis.

Figure 3

(A) An electrochemical immunosensor using a AuNP-RGO nanocomposite to detect NSE [32]. (B) Fabrication and modification process of the multi-parameter electrochemical paper-based aptasensor [33]. (C) TiO₂-based PEC biosensor for detecting AFP [34].

Figure 4

(A) HRP-Au NR bioconjugate for signal amplification of AFP [39]. (B) ISGNP-labeled ALP for AFP detection [40].

Figure 5

(A) Schematic illustration of an aptasensor for the detection of CEA based on Exo III and HCR dual signal amplification [41]. (B) ECL detection of CEA based on the target recycling amplification strategy [42]. (C) Preparation procedures for dendrimer-like DNA nanoassembly [43].

Figure 6

(A) AuNP/PGNR/GCE electrochemical immunosensor for the detection of AFP [53]. (B) Synthesis of Apt2-CNT-PFcGE via ROP [54].

Figure 8

(A) The operational principle of electrochemical μPADs [127]. (B) AN electrochemical immunosensor for the simultaneous detection of CEA and AFP [132].