ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

Type of article: bibliographic review https://doi.org/10.47460/athenea.v6i20.93

Advances in zinc oxide nanobiosensors for medical diagnostics:

morphologies, mechanisms and applications

Luis A. Pescador Nieves*

https://orcid.org/0009-0000-5557-4915

pescador 163723@students.pupr.edu

Polytechnic University of Puerto Rico

San Juan - PR USA

Bryan D

ıaz Estrada

https://orcid.org/0009-0002-1970-9450

diaz 93168@students.pupr.edu

Polytechnic University of Puerto Rico

San Juan - PR USA

*Correspondence author: pescador 163723@students.pupr.edu

Received (27/11/2024), Accepted (06/02/2025)

Abstract. Zinc oxide (ZnO) nanostructures present remarkable morphological, chemical and electrical

properties, including a large surface area, semiconductor behavior and a high isoelectric point, position-

ing them as ideal for biosensing applications. This review outlines the recent advances (2022-2024) in

ZnO-based nanobiosensors for medical applications, based on a selection of peer-reviewed, open-access

experimental studies extracted from databases including IEE Xplore, Scopus and ScienceDirect. A va-

riety of ZnO morphologies, including nanoﬂowers, nanorods, nanosheets and nanoparticles have made

possible the development of piezoelectric, electrochemical, optical and ﬁeld-eﬀect transistor biosensors.

Experimental data reveal that ZnO-based nanotechnologies achieve rapid detection of lactate, cancer

biomarkers, glucose and infectious disease antigens, demonstrating lower detection limits and enhanced

sensitivity. Emerging strategies, such as noble metal decoration and integration into wearable platforms

or microﬂuids, have improved eﬃciency and clinical applicability. ZnO-based nanostructures therefore

serve as a promising basis for the next generation of continuous monitoring and point-of-care systems.

Keywords: zinc oxide, nanobiosensor, medical diagnostic.

Avances en nanobiosensores de ´oxido de zinc para diagn´ostico

m´edico: morfolog´ıas, mecanismos y aplicaciones

Resumen. - Las nanoestructuras de

oxido de zinc (ZnO) presentan buenas propiedades morfol

ogicas,

ımicas y el

ectricas, como gran

area superﬁcial, comportamiento semiconductor y alto punto isoel

ectrico,

lo que las hace ideales para biosensores. Esta revisi

on aborda avances recientes (2022–2024) en

nanobiosensores de ZnO para diagn

ostico m

edico, bas

andose en estudios experimentales peer-review

y open-access de IEEE Xplore, Scopus y ScienceDirect. Diversas morfolog

ıas de ZnO como nanoﬂo-

res, nanovarillas, nanol

aminas y nanopart

ıculas han permitido desarrollar biosensores piezoel

ectricos,

electroqu

ımicos,

opticos y de efecto de campo. Los resultados muestran detecci

on r

apida de lactato,

biomarcadores oncol

ogicos, glucosa y ant

ıgenos pat

ogenos, con l

ımites de detecci

on menores y sensibili-

dad mejorada. Estrategias emergentes, como decoraci

on con metales nobles e integraci

on en dispositivos

port

atiles o microﬂuidos, aumentan la eﬁciencia y viabilidad cl

ınica. En conjunto, las nanoestructuras

de ZnO se perﬁlan como plataforma prometedora para la siguiente generaci

on de sistemas de monitoreo

continuo y diagn

ostico en el punto de atenci

on.

Palabras clave:

oxido de zinc, nanobiosensores, diagn

ostico m

edico.

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

I. INTRODUCTION

Biosensors are analytical devices with the capability of combining a physiochemical

transducer with an element of biological recognition for the detection of speciﬁc analytes

and transforming this interconnection into a quantiﬁable signal [1]. This form of sensors

represents a fundamental tool for modern medical diagnostics due to their high precision,

Immediate respond and ability to provide real time and point of attention monitoring.

Recent advancements in nanotechnology have caused an increment in the development

of nanobiosensors, which incorporate nanomaterials mainly less than 100nm in size to

strengthen the biosensors execution by enhancing the electron transfer rates, biomolecule

immobilization efﬁciency and surface area [1].

Different types of nanomaterials like graphene, gold nanoparticles (AuNPs), carbon

nanotubes (CNTs), and metal oxide nanostructures have shown remarkable beneﬁts in

biosensing applications [2]. These materials allow lower detection limits, a faster reaction

time and higher sensitivity in comparison to traditional bulk materials. The nanoscale

dimensions for these devices enable a productive transduction of biological signals and

support the miniaturization process for the incorporation of wearable or portable diag-

nostic system devices. More precisely, such forms of nanotechnology have led to signiﬁ-

cant advancements in optical, piezoelectric and electrochemical biosensors [2].

In comparison to the large range of nanomaterials on the market, zinc oxide (ZnO)

has proven to be a potential candidate for nanobiosensing technologies. ZnO provides a

mixture of valuable characteristics, including a large bandgap (∼ 3.3 eV), chemical stabil-

ity, a high isoelectric point (∼ 9.5)) and an excellent biocompatibility, contributing to its

status as suitable for the immobilization of low isoelectric point (IEP) biomolecules like

antibodies and enzymes [2]. In addition, ZnO can be engineered into a wide range of

nanostructures like nanoﬂowers, nanowires, nanorods and nanosheets, using ﬁnancially

sustainable and industrially scalable methods for example: sol-gel processes, sputtering

and hydrothermal synthesis [3][4] Furthermore, the variation on ZnO structures mor-

phologically speaking helps with the increment of the surface area and promote stronger

afﬁnities with analytes, contributing to greater selectivity and sensitivity in biosensors

made of ZnO nanostructures [4].

This review aims to provide an overview of recent advances (2022-2024) in ZnO-based

biosensors used for medical diagnostics. On top of that, the review underscores proper-

ties that make ZnO-based biosensors highly favorable in a unique way, highlights key

uses for glucose monitoring, cancer biomarker sensing, infectious disease detection, and

explores methods for device fabrication and biomolecule functionalization. Lastly, this

document describes current challenges in integration, reproducibility and stability, and

addresses future scenarios for real-world implementation and clinical technology trans-

fer of ZnO-based biosensing devices.

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

II. STRUCTURAL AND FUNCTIONAL BASIS OF ZNO

NANOBIOSENSORS

A. Physiochemical properties of ZnO for biosensing

ZnO nanostructures have a unique mixture of electrical, chemical, and morphological

properties that make them suitable for biosensor applications.

1. High isoelectric point and biomolecule adsorption – exhibits an isoelectric point

of approximately 9.5, making its surface positively charged under physiological pH

conditions [5]. This favors the electrostatic adsorption of enzymes and proteins re-

sulting in a stable microenvironment, facilitating both preservation of biomolecular

activity and efﬁcient electron transfer.

2. High surface-to-area-to-volume ratio – this enables the anchoring of biological

molecules, leading to enhanced detection of a speciﬁc target analyte [5]. The ability

to modify morphology and surface chemistry plays a critical role in modulating the

biosensor’s selectivity, sensitivity, and operational range.

Table 1 presents the different morphologies of ZnO in biosensing applications. Each

ZnO morphology offers unique structural and functional features that enhance biosen-

sor performance. These structures vary in dimensionality, surface characteristics, and

electron transport capabilities.

B. Electrical and optical properties for sensor stability

ZnO is a wide-bandgap semiconductor with a bandgap energy of 3.37 eV, which means

it can operate at high voltages and under strong electric ﬁelds without undergoing electri-

cal breakdown [6]. This property ensures the long-term electrical stability of biosensors,

especially those used in biological ﬂuids or high-impedance environments.

ZnO also exhibits strong photoluminescence for sensitive optical detection due to its

high exciton binding energy (60meV) [6]. This photoluminescence emission typically

occurs in the UV and visible blue range and is highly sensitive to changes at the surface

of the nanostructure enabling real-time monitoring of biomolecular interactions.

C. Signal transduction mechanismss

1. Electrochemical transduction – electrochemical biosensors operate by converting

biochemical interactions into electrical signals. The ZnO nanostructures act as elec-

trode materials or electrode modiﬁers due to their moderate conductivity, high sur-

face area, and ability to stabilize redox-active biomolecules. They facilitate efﬁcient

electron transfer between the enzyme’s active site and the electrode [7].

2. Optical transduction – the ability to interact with light and produce measurable

changes in their optical emission properties upon biomolecular recognition. When

a target biomolecule binds to the ZnO surface, it modiﬁes the surface electronic

structure or local environment affecting the photoluminescence behavior [4, 8].

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

Tabla 1. Morphologies of ZnO in biosensing applications.

Morphology Dimensio-

nality

Structure

Description

Key

Functional

Features

Biosensor

Application

Nanoparti-

cles (NPS) [4]

0D (zero-

dimensional)

Spherical or

quasi-

spherical

particles with

nanoscale

diameters

High density

of surface

atoms;

excellent for

maximizing

surface

interactions

Antibody

/aptamer-

based sensors;

electrochemi-

cal detection

Nanorods/

Nanowires

[4]

1D (one-

dimensional)

Vertically

aligned or

elongated

rod-shaped

structures

Direct,

continuous

electron

transport

paths; fast

redox

reactions

Enzyme-

based glucose,

uric acid, and

cholesterol

sensors

Nanosheets

[4]

2D (two-

dimensional)

Thin, ﬂat

plate-like

layers with

polar surface

exposure

Enhanced

binding of

charged

biomolecules;

ﬂexible

integration

Wearable

patch sensors;

DNA/protein

electrochemi-

cal sensors

Nanoﬂowers

/ Porous

structures [4]

3D (three-

dimensional)

Branched

assemblies

with high

surface area

and inner

voids

High

target-binding

molecule

capacity;

improved

analyte

diffusion and

transport

SARS-CoV-2

gene sensors;

cancer

biomarker im-

munosensors

3. Piezoelectric / acoustic transduction – thin ﬁlms or nanostructures act as mass-

sensitive platforms causing an analyte (such as a protein or virus) when bonded to

a functionalized ZnO surface, it causes a measurable mass change [9]. Due to ZnO’s

strong piezoelectric coefﬁcient and high acoustic velocity, even minute changes in

mass lead to detectable frequency shifts, enabling highly sensitive, label-free detec-

tion of biomolecules in real time.

4. Field-effect transistor (FET) transduction – ZnO nanowires or thin ﬁlms form the

semiconducting channel between the source and drain electrodes [6][10]. These

channels are functionalized with biorecognition molecules. When a charged an-

alyte (such as a protein, ion, or DNA) binds to the surface, it modiﬁes the local

electric ﬁeld, affecting the charge carrier density in the ZnO channel and the con-

ductivity of the device [6]. This results in a modulation of the drain-source current,

which serves as the detection signal [11][12][13][14].

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

III. METHODOLOGY

This review is based on an extensive analysis of various scientiﬁc articles released be-

tween 2022 and 2024, directing attention to the applications of ZnO nanotechnologies

in biosensors disease detection. Importantly, it covers both peer-reviewed reviews and

open-access articles focusing on surface modiﬁcation approaches for ZnO-based biosen-

sors surface, key aspects of biosensing, and recent experimental investigations into its

capabilities in optical and electrochemical sensors. The articles used in this review were

selected based on their consistency with the study’s focus [15], clinical relevance, and

uniqueness, relying on sources like Springer, ScienceDirect, ELsevier and literature databases

including IEEE Xplore and Scopus.

Tabla 2. Key contributions in ZnO-based biosensors

Ref. Year Key Contribution

[9] 2024 Development of a self-powered lactate biosensor based on

the piezoelectric effect of ZnO nanowires

[10] 2023 Non-enzymatic glucose sensor using Ag-decorated ZnO

nanorods, ≈ 1.3 µM, high sensitivity

[14] 2023 Electrochemical immunosensor for anti-PSA employing

spherical ZnO structures, achieving nanomolar detection

[16] 2023 Microﬂuidic platform with ZnO nanorods for point-of-care

dengue (DENV-3) immunoﬂuorescent detection

[6] 2022 Review of 2D ZnO nanostructure-based biosensors, cover-

ing synthesis through device fabrication and performance

metrics

IV. RESULTS

Recent studies have shown that ZnO structures can be adapted into several mor-

phologies – from one-dimensional (1D) nanowires and nanorods to two-dimensional

(2D) nanosheets and hierarchical nanoarchitectures – to improve the bio detection per-

formance [11]. These modiﬁed forms of ZnO offer a large surface area and a high iso-

electric point (favorable surface chemistry) for the immobilization of bioreceptors, which

translates into high sensitivity and low limits of detection (LOD) in medical diagno-

sis [11]. This section in speciﬁc examines the experimental ﬁndings from 2022 to 2024

on ZnO-based biosensing devices targeted at a wide range of medically relevant ana-

lytes, including pathogens, glucose, cancer biomarkers and hormones. The emphasis

of this section is placed on new ZnO-based nanostructures (e.g., 2D nanosheets, ver-

tically aligned nanorods, ﬂower-like hierarchical structures), various sensor conﬁgura-

tions (optical, ﬁeld-effect transistor, electrochemical), key performance indicators (LOD,

linear range, sensitivity), and the demonstrated potential for real-life applications (point-

of-care devices and wearable devices). Table 3 outlines exemplary ﬁndings from recent

open-access studies.

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

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Tabla 3. Performance comparison of ZnO-based biosensors

Analyte ZnO Nanos-

tructure

Detection

Method

Linear

Range

LOD Sensitivity

(en-

zymatic)

Waxberry-like

ZnO micro-

spheres [12]

Amperometric

enzyme

biosensor

0.15–15

0.115

µM

–

(non-

enzymatic)

ZnO nanopar-

ticles on

MWCNTs [13]

Amperometric

enzyme-free

sensor

1–20 mM – –

Glucose High-aspect-

ratio ZnO

nanorods [5]

Amperometric

enzyme

biosensor

– – Fastest re-

sponse (∼5s)

Glucose Ag-decorated

ZnO

nanorods [10]

Amperometric

enzyme-free

biosensor

50–175 µM 1.3 µM 2792µA

/(mM·cm

)

Anti-PSA

antibody

Spherical ZnO

nanostruc-

tures [14]

Electrochemical

immunosen-

sor

– ∼1–2

Higher with

spherical ZnO

CA-125 ZnO–Au

hybrid

nanorods [15]

Immunosensor

(DPV)

– ∼2.5

ng/µL

∼100× better

than ELISA

Dengue

virus anti-

gen

ZnO nanorods

in microﬂuidic

chip [16]

Immuno-

ﬂuorescence

detection

∼3.1×10

−4

– 3.1×10

ng/mL

3.1×10

−4

ng/mL

2.7× higher

signal vs ﬂat

glass

Lactate ZnO nanowire

array on Ti

substrate [9]

Piezoelectric

enzymatic

biosensor

Up to 27

∼1.3

Self-powered

signal from

LOx reaction

A. ZnO Nanobiosensors for Glucose and H

Monitoring

Signiﬁcant advances in biosensing have been led by ZnO-based nanostructures, espe-

cially in the detection of hydrogen peroxide (H

) and glucose. ZnO-based micro-

spheres resembling waxberries and with a large surface area for enzyme immobilization,

making possible a horseradish peroxidase (HRP) biosensor showing a linear range of

0.15–15 mM and a low detection limit of ∼0.115 µM for hydrogen peroxide [12]. In an-

other study, it was showed that ZnO nanoparticles anchored onto carbon nanotubes pro-

duced stable, enzyme-free amperometric sensing of hydrogen peroxide, with the perfor-

mance largely dictated by the ZnO structural form (spherical or rod-shaped) [13]. These

investigations underscore how nanostructures design contributes to enhanced biosensor

performance.

In addition, the morphology of ZnO nanorods for glucose sensing was modiﬁed,

revealing that thinner, longer structures facilitated higher enzyme immobilization and

resulted in the fastest amperometric response (5s) and the highest performance [5]. In

recent studies, an enzyme-independent glucose sensor with the use of vertically aligned

ZnO-based nanorods was modiﬁed with silver nanoparticles. Their device demonstrated

an outstanding sensitivity (2792 µA/(mM·cm

)), with a linear range from 50 µM to 175

µM and a low LOD of 1.3 µM [10]. These ﬁndings validate that ZnO surface and structure

modiﬁcation (e.g., noble metal decoration) play a critical role in biosensors efﬁciency.

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

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Vol.6, Issue 20, (pp. 20-29)

B. ZnO-Based Sensors for Cancer Biomarkers

In a recent investigation, a ZnO-based sensor made for the detection of the anti-prostate-

speciﬁc antigen (anti-PSA) antibodies was developed and this device achieved nanomo-

lar detection limits, while evaluating and contrasting different types of ZnO morphology

to enhance sensitivity [14]. Their results demonstrated that the morphology exhibiting

superior sensitivity was the spherical nanostructures, outperforming rod-like forms. A

design of ZnO-Au nanohybrid immunosensor for CA-125 (a biomarker for ovarian can-

cer) achieved a detection limit of 2.5 ng/µL, close to 100× more sensitive than conven-

tional immunoblots [15]. These novel ﬁndings have shown the ZnO’s growing impact in

non-invasive cancer diagnosis.

C. ZnO Nanobiosensors for Infectious Disease Diagnostic

A notable example that illustrates the potential of ZnO nanomaterials in infectious dis-

ease diagnostics is developing a ZnO nanorod-integrated microﬂuidic immunoﬂuores-

cence platform for the detection of Dengue virus serotype 3 (DENV-3) [16]. This study

is especially relevant for low-resource settings and point-of-care diagnostics due to its

sensitivity, speed, and minimal sample requirements.

The ZnO nanorods were synthesized via a seed-assisted hydrothermal growth pro-

cess, resulting in vertically aligned structures with a predominant (002) crystal orienta-

tion. The ZnO nanorods functioned as an immobilization surface for speciﬁc monoclonal

antibodies (mAbs) to the DENV-3 envelope protein. Functionalization was achieved

using 3-glycidyloxypropyl trimethoxysilane (GPTMS) which is a silane linker that co-

valently bonds the antibodies to the ZnO surface. Among different surface treatments

tested, ZnO modiﬁed with 4% GPTMS yielded the highest ﬂuorescence intensity [16].

The mechanism of signal generation is based on optical transduction, where the amount

of ﬂuorescent signal directly correlates to the concentration of antigen present on the ZnO

surface. The ZnO nanorods play a critical role by:

1. Providing a high surface area for mAb immobilization

2. Enhancing binding efﬁciency and signal ampliﬁcation

3. Supporting stable, reproducible ﬂuorescence output

This study is a strong example of how ZnO nanorod morphology can be strategically

manipulated to improve biosensor performance through surface chemistry optimization

and microﬂuidic integration. The work demonstrates that ZnO nanostructures not only

enhance biomolecular binding but also enable label-based ﬂuorescence detection at ex-

tremely low analyte concentrations.

D. Hormone and Metabolite Sensors with Nanostructures

A recent study presents a novel approach to lactate detection using a self-powered ZnO

nanowire-based biosensor that represents the multifunctionality of ZnO in wearable di-

agnostics [9]. The authors developed a biosensing device in which ZnO nanowire arrays

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

were hydrothermally grown on a titanium substrate. The ZnO surface was then func-

tionalized with lactate oxidase (LOx), an enzyme that catalyzes the conversion of lactate

into pyruvate and hydrogen peroxide [9]. What distinguishes this work is its use of

the piezoelectric properties of ZnO to enable energy-autonomous sensing. The detection

mechanism is based on the piezo-enzymatic coupling effect. Mechanical deformation

(e.g., pressure or bending) of the ZnO nanowires generates a piezoelectric voltage due to

lattice polarization. In the presence of lactate, the enzyme-catalyzed reaction alters the

local ionic environment at the ZnO surface, which modulates the piezoelectric signal out-

put. The magnitude of the output voltage correlates with lactate concentration, allowing

real-time, quantitative measurement without external power or labeling agents.

This study represents an important advancement in self-powered biosensing and

demonstrates the potential of ZnO as a material platform for mechanically responsive,

label-free, and wearable diagnostics. The concept of piezo-enzymatic sensing offers a

path forward for battery-free devices in personalized healthcare. Furthermore, the au-

thors demonstrated a clear integration strategy between material design (ZnO nanowires),

biofunctionalization (LOx), and mechanical actuation.

E. Toward Real-World Implementation

ZnO has been positioned as a leading material in next generation biosensors due to

its compatibility with chemical stability, biocompatibility and scalable fabrication tech-

niques (e.g., screen printing, hydrothermal growth). These ZnO-based nanobiosensors

are more frequently tailored for wearables and point-of-care deployment. A thorough

review by Zhou et al described ZnO-based enzyme biosensors and substantiated the ma-

terial’s broad relevance to clinical diagnostics.

Fig. 1. Representative ZnO nanostructure morphologies and biosensor architectures.

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics

ISSN-e: 2737-6419

Period: April-June 2025

Athenea Journal

Vol.6, Issue 20, (pp. 20-29)

CONCLUSIONS

ZnO nanobiosensors demonstrate exceptional physicochemical properties that position

them as a root for the future development of advanced biosensing platforms. Their wide

bandgap, high isoelectric point, and morphological diversity provide versatility for engi-

neering medical diagnostic devices. The reviewed studies validate that strategic manip-

ulation of ZnO nanostructures can signiﬁcantly expand their applicability beyond tradi-

tional laboratory settings into real-time, portable, and point-of-care diagnostic settings.

The adaptability of ZnO opens pathways for developing next-generation biosensors

capable of multiplex detection, self-powered operation, and miniaturization. Future ex-

ploration should focus on overcoming challenges related to long-term stability, scalabil-

ity, and clinical validation to ensure successful translation into healthcare practice.

ZnO-based nanobiosensors not only offer promising routes for disease diagnosis but

also inspire broader applications in personalized medicine, continuous health monitor-

ing, and environmental sensing.

ACKNOWLEDGEMENT

The authors acknowledge the Polytechnic University of Puerto Rico for providing ac-

cess to scientiﬁc databases and institutional support during the completion of this review.

Appreciation is also extended to the scientiﬁc journals and open-access platforms that en-

abled comprehensive access to current literature on ZnO-based biosensing technologies.

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AUTHORS

Luis A. Pescador Nieves is a master’s student in Biomedical Engineering at

the Polytechnic University. He holds a bachelor’s degree in biology and has

a strong interest in medical technology and innovation. As a passionate

learner, he strives to develop impactful biomedical applications that beneﬁt

the society.

Bryan D. D

ıaz Estrada is a master’s candidate in Biomedical Engineering

at the Polytechnic University, building on his bachelor’s degree in Cell

and Molecular Biology. He brings a fresh perspective to medical device

research and is eager to apply foundational engineering principles to real-

world healthcare challenges. Passionate about technological innovation, he

aspires to translate academic learning into impactful solutions that improve

patient outcomes and advance the ﬁeld of biomedical engineering.

Pescador L. and D´ıaz B. Advances in zinc oxide nanobiosensors for medical diagnostics