# Label-Free Electrochemical Biosensors: An Updated Perspective Focused on Genosensing, Multiplexing, and Commercial Potential

**Authors:** Jefferson H. S. Carvalho, Marcus A. S. Catai, Lucas V. Bertolim, Rafaela C. Freitas, Jessica R. Camargo, Laís C. Brazaca, Bruno C. Janegitz

PMC · DOI: 10.3390/bios16020098 · Biosensors · 2026-02-04

## TL;DR

This review discusses label-free electrochemical biosensors for disease detection, focusing on their potential for early, low-cost, and portable diagnostics.

## Contribution

The paper provides an updated perspective on genosensing, multiplexing, and commercial challenges in label-free electrochemical biosensors.

## Key findings

- Label-free electrochemical biosensors offer high sensitivity and low-cost architectures for point-of-care testing.
- DNA biosensors and multiplexed configurations show promise for detecting disease biomarkers.
- Barriers to commercialization include bioreceptor stability, limited real-sample validation, and scalable manufacturing challenges.

## Abstract

The increasing impact of infectious, cardiovascular and neurodegenerative diseases has intensified the demand for early and decentralized diagnostics. Label-free electrochemical biosensors are promising candidates, offering high sensitivity, low reagent consumption and miniaturizable, low-cost architectures for point-of-care (PoC) testing. This review summarizes advances in immobilization strategies, recognition elements such as DNA, antibodies, aptamers, and molecularly imprinted polymers, as well as electrode platforms including glassy carbon, screen-printed, and 3D-printed systems, with an emphasis on DNA biosensors, multiplexed configurations, and applications to disease biomarkers. Beyond analytical performance, we critically examine the barriers that keep most devices at the proof-of-concept stage, including bioreceptor stability and immobilization, limited validation in real samples, reliance on conventional materials, challenges in scalable manufacturing, transport, and storage, and the absence of fully integrated PoC systems. Finally, we discuss significant advances in sensitivity, reproducibility, and application to real samples, but note that translation to real-world use and commercialization remains limited.

## Full-text entities

- **Genes:** POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, HTT (huntingtin) [NCBI Gene 3064] {aka HD, IT15, LOMARS}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, IVNS1ABP (influenza virus NS1A binding protein) [NCBI Gene 10625] {aka ARA3, FLARA3, HSPC068, IMD70, KLHL39, ND1}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, TNNI3 (troponin I3, cardiac type) [NCBI Gene 7137] {aka CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, PARK7 (Parkinsonism associated deglycase) [NCBI Gene 11315] {aka DJ-1, DJ1, GATD2, HEL-S-67p}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, SFTPB (surfactant protein B) [NCBI Gene 6439] {aka PSP-B, SFTB3, SFTP3, SMDP1, SP-B}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, MIR206 (microRNA 206) [NCBI Gene 406989] {aka MIRN206, miRNA206, mir-206}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** HIV/AIDS (MESH:D015658), Zika (MESH:D000071243), sepsis (MESH:D018805), infectious diseases (MESH:D003141), nerve cell degeneration (MESH:D009410), breast cancer (MESH:D001943), sickle cell disease (MESH:D000755), heart diseases (MESH:D006331), myocardial infarction (MESH:D009203), cardiovascular diseases (MESH:D002318), infected (MESH:D007239), COVID-19 (MESH:D000086382), death (MESH:D003643), viral infections (MESH:D014777), coronavirus (MESH:D018352), Hereditary Huntington's disease (MESH:D030342), visceral leishmaniasis (MESH:D007898), Ebola (MESH:D019142), Dengue (MESH:D003715), AD (MESH:D000544), poisoning (MESH:D011041), cancer (MESH:D009369), infectious, cardiovascular and neurodegenerative diseases (MESH:D019636), injury to (MESH:D014947), prostate cancer (MESH:D011471), influenza (MESH:D007251), sleep disturbances (MESH:D012893), Parkinson's (MESH:D010300)
- **Chemicals:** 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (MESH:D005022), GA (MESH:D005976), okadaic acid (MESH:D019319), saxitoxin (MESH:D012530), MXenes (MESH:C000723374), CdS (MESH:D002104), glucose (MESH:D005947), EDC (MESH:C024565), Sulfo-LC-SPDP (MESH:C109849), CS (MESH:D002586), CO2 (MESH:D002245), polystyrene (MESH:D011137), pyrrole (MESH:D011758), PLA (MESH:C033616), polyvinyl alcohol (MESH:D011142), titanium (MESH:D014025), carbon nanotube (MESH:D037742), PoCs (MESH:C042234), tiamulin (MESH:C014224), epoxy (MESH:D004853), graphene (MESH:D006108), AgNPs (-), CNF (MESH:C071110), ITO (MESH:C109984), CB (MESH:C063451), poly-adenine (MESH:C000628261), cylindrospermopsin (MESH:C089595), oligonucleotide (MESH:D009841), polydopamine (MESH:C568283), Ag (MESH:D012834), 6-mercapto-1-hexanol (MESH:C503488), microcystin-LR (MESH:C057862), ZnO (MESH:D015034), N-hydroxysuccinimide (MESH:C001426), Cys (MESH:D003543), polyaniline (MESH:C416807), water (MESH:D014867), Methylene blue (MESH:D008751), atrazine (MESH:D001280), lactate (MESH:D019344), MOFs (MESH:C040750), PPy (MESH:C067635), Ferrocene (MESH:C004998), thiophene-2-carboxylic acid (MESH:C550746), anatoxin-alpha (MESH:C509783), PNA (MESH:D020135), carbon (MESH:D002244), polymer (MESH:D011108), Pt (MESH:D010984), MoS2 (MESH:C082964), Metal (MESH:D008670), gold (MESH:D006046), chitosan (MESH:D048271)
- **Species:** Dengue virus (no rank) [taxon 12637], Staphylococcus aureus (species) [taxon 1280], Mycobacterium tuberculosis (species) [taxon 1773], Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Escherichia coli O157:H7 (no rank) [taxon 83334], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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## References

173 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938614/full.md

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Source: https://tomesphere.com/paper/PMC12938614