Integrating Biosensors and

Nanotechnology for Advanced Diagnostics

Prof. Dr. Rajiv Dutta, M.Tech (IIT-Kgp), Ph.D (BITS-Pilani)

Fellow of the Royal Society of Biology, London, UK
Fellow of the Institute of Physics, London, UK
Fellow of the American Academy of Science & Technology, Reston, USA

Research & Innovation and Dean, School of Biological Engineering & Life Sciences
Shobhit University, Gangoh, Saharanpur
 Day 3: Advanced Concepts of Biosensors in
Diagnostics
• Advanced Nanotechnology in Diagnostics
 Cutting-edge developments
 Emerging trends in nanotechnology and diagnostics
• Challenges and Ethical Considerations
 Ethical issues in biosensor development
 Regulatory considerations
Cutting-Edge Biosensors in Healthcare
• Biosensor applications for diabetes
• Biosensor applications for cardiovascular diseases
• Biosensor applications for cancer
• Biosensor applications for Parkinson’s disease
• Biosensor applications for Alzheimer’s
• Development of wearable sensors
 Healthcare applications of biosensors
Following essential conditions must be met:

1. Specific biomarkers to differentiate between normal and infected

states
2. Techniques to identify and differentiate them
3. Preferentially noninvasive monitoring approaches for these
biomarkers
4. Rapid response times, user friendliness, affordability, and
5. The ability to create simple and disposable devices suitable for mass
production
 Biosensor applications for diabetes
• Advances in microdialysis or ultrafiltration technology are employed in
conjunction with glucose-detecting biosensors
• To monitor their blood glucose levels, diabetes patients rely on glucose test
strips
• Existing test strips often suffer from cost and durability limitations
• Thus, scientists have created an electrical sensor constructed from paper that
has been molecularly imprinted with glucose recognition sites
• This non-enzymatic glucose biosensor has the potential to reduce medical
expenses and enhance accessibility in underserved areas
• This chip combines luminol-encapsulated metal–organic frameworks and
glucose oxidase (GOx) on filter paper, exhibiting a color change from purple to
brown in the presence of glucose
• This biosensor has a low limit of detection (LOD: 0.87 mM)
 Very Recently
• The development of copper(I) halide and copper(II) oxide nanoparticles
(CuBr@CuONPs) on Cu foils has revolutionized electrocatalytic glucose detection.
• This electrode has a wide linear range, and remarkable electrocatalytic activity.
• Furthermore, a strong link between blood glucose levels has been confirmed by
validation trials utilizing salivary samples.
• Because of this, the noninvasive glucose monitoring system using the NP-based
electrode has tremendous potential for use by diabetic patients
• Salivary glucose levels in diabetics can be detected noninvasively with a
toothbrush containing an amperometric biosensor. The sensor electrodes, made
of carbon graphite and Ag/AgCl inks, demonstrated successful glucose detection
within a concentration range of 0.18 mM to 5.22 mM in less than 5 minutes
• Glucose sensors utilizing chitosan-capped ZnS-doped Mn nanoparticles provide
fast and accurate detection. Among the tested materials, chitosan-capped ZnS-
doped with Mn at 1% weight demonstrates superior sensitivity, selectivity, and
stability
 Biosensor applications for cardiovascular
diseases
• Research on cardiovascular disease relies mostly on biosensors that gauge
cholesterol levels. Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) are
frequently used in these biosensors as sensor components, allowing for the
measurement of both free cholesterol and total cholesterol
• An effective method for precisely determining cholesterol levels in the system is
electrochemical transducers
• MicroRNA-21 (miRNA-21), a biomarker linked to cardiovascular disorders, has
been investigated as a potential target for a carbon nanodot-based biosensor.
The carbon nanodots (CNDs) that were employed in the biosensor were created
using a quick and eco-friendly process. The CNDs had advantageous optical and
surface characteristics that made them co-reactant agents in the
electrochemiluminescent process of the biosensor.
• The biosensor immobilized a complementary polynucleotide on a single-use gold
electrode to achieve sensitive detection of miRNA-21.
• An aptasensor with a LOD of 0.01 ng/mL that can measure troponin T
(TnT) levels and diagnose myocardial infarction at an early stage.
• Myocardial infarction-related mortality and the decline in the
prevalence of patients with cardiac failure
• This aptamer-based biosensor has the potential to have a large
positive effect on healthcare
• The implications of this technology are far-reaching, holding
tremendous promise for integrating tele-health into our daily lives
and advancing the field of wearable technology
 Biosensor applications for cancer
• There have been numerous successful biosensor studies for cancer
diagnosis, one of which utilized an ultrasensitive DNA electrochemical
biosensor
• This biosensor employed a carbon paste electrode amplified with ZIF-8 and
1-butyl-3-methylimidazolium methanesulfonate to detect the anticancer
drug mitoxantrone in aqueous solutions
• By exploiting the interaction between mitoxantrone and guanine bases of
ds-DNA, as confirmed through docking research, the biosensor exhibited
robust catalytic effects and precise determination capabilities
• With a LOD of 3.0 nM, it successfully detected mitoxantrone across a wide
concentration range of 8.0 nM to 110 M
• Pharmacological investigations have brought attention to viscumin, a
plant-derived protein with potential applications in cancer treatment.
• In a recent study, scientists utilized a 9-mer peptide sequence as a
template to create a molecularly imprinted polymer.
• Under the influence of ultraviolet light, the functional monomer
formed hydrogen bonds with the epitope, resulting in the polymer’s
structure.
• Subsequently, the epitope was extracted from the polymer surface
using a solution of acetic acid and sodium dodecyl sulfate (SDS).
When evaluated in blood plasma and urine, the nano-biosensor
exhibited selectivity
In a recent work
• Utilizing methotrexate (MTX) as a model system, an analytical method
for detecting an anticancer treatment in whole blood was developed.
• The electrode surface of the biosensor used a unique modified
carbon nanotube. Due to the cooperative action of the nitrogen-CNT,
this composite displayed excellent electrical conductivity and catalytic
activity.
• With low LOD (45 nM), a broad detection range (0.01–540 M),
excellent selectivity, and long term stability for MTX detection
• The modified screen-printed electrodes (SPE) with WP/N-CNT
demonstrated impressive performance, making it ideal for efficient
and mobile MTX detecting, even in blood samples
 Biosensor applications for Parkinson’s disease
• Parkinson’s disease (PD) is a degenerative brain condition that causes a
variety of non-motor difficulties, including cognitive decline, mental
disorders, sleep disturbances, and sensory disturbances, in addition to
motor symptoms like slow activity, shaking hands, strength, and
difficulties with balance
• A rapid and precise miRNA biosensor was developed using the target-
triggered three-way junction (3-WJ), terminal deoxynucleotide
transferase (TDT)/ Nt.BspQI, and activated copper nanoparticles (CuNPs)
• The biosensor successfully detected target miRNAs down to a minimal
detection limit of 1 fM at 1.75 h
• By examining whole blood RNA samples from patients with Parkinson’s
disease, its applicability was proven
• A highly sensitive and specific method for the early diagnosis of Parkinson’s
disease was proven using the SPR sensor, which allowed for the accurate
quantification of -syn in diluted serum samples
• Alpha-synuclein can be detected in serum samples using a surface plasmon
resonance (SPR) biosensor that has been created utilizing magnetite
nanoparticles (Fe3O4 NPs) and matched antibodies.
• The sensitivity of the SPR is greatly improved by depositing Fe3O4 NPs on
the surface of Au at a high density, enabling a detection limit of 5.6 fg mL−1,
20.000-fold lower than commercial Enzyme-linked immunosorbent assay
(ELISA)
• Highly sensitive electrochemical neurobiosensor by utilizing an
electrode doped with a nanocomposite of multiwalled carbon
nanotubes (MWCNT) and gold nanoparticles (AuNP).
• This nanostructure based electrode was employed to detect DJ-1, a
protein responsible for mitigating oxidative stress and managing
mitochondrial dysfunction in Parkinson’s disease
• The neurobiosensor showed a LOD of 0.5 fg mL−1 and range of 4.7–
4700 fg mL−1
• With its ability for selective determination, the biosensor shows
potential for identifying DJ-1 protein in cerebrospinal fluid (CSF) and
saliva
• Developed a minimally invasive biosensor based on a flexible
differential micro-needle array (FDMA) to accurately monitor the
dynamic concentration of levodopa (L-Dopa) in PD patients and lower
the risk of consequences
• The FDMA biosensor, which has two functional electrodes, has great
anti-interference performance when it comes to separating out
interfering chemicals from L-Dopa.
• A viable solution for continuous and less invasive monitoring of L-
Dopa levels in PD patients, the biosensor shows a wide linear dynamic
range, good sensitivity, and long-term stability
• Anthocyanins, pigments known as flavonoid present in fruits and
vegetables, were studied for their effects on amyloid fibrils linked to
neurodegenerative diseases such as Parkinson’s and Alzheimer’s
diseases. Using total-internal-reflection-fluorescence microscopy
(TIRFM)
• They were able to directly observe how anthocyanins broke down
amyloid beta (Abeta) fibrils
• The findings showed that the number of hydroxyl groups in the
anthocyanin’s six-membered ring B determines the disassembly
activity of Abeta fibrils, with delphinidin-3-galactoside having the
maximum disassembling activity
• The significance of hydroxyl groups and shows how TIRFM-QCM can be
used to investigate chemical interactions with amyloid fibrils
 Biosensor applications for Alzheimer’s
• Dementia is a collection of brain disorders causing progressive and severe
loss of cerebral disorders, including memory, thinking, behavior, and
emotions
• Researchers developed a surface plasmon resonance imaging (SPRi)-based
biosensor to evaluate extracellular vesicles (EVs) in plasma samples from
Alzheimer’s disease (AD)
• Patients and normal individuals, successfully identifying and identifying EV
populations formed by various cell types.
• The quantity and particular traits of the EV populations were significantly
different
• AD patients and healthy controls, according to comparisons between their
EV profiles
• Highly flexible nanopillar-based electrochemical biosensors with a
significantly large surface area by depositing gold on a polyurethane
substrate. The biosensors were made biocompatible through the
utilization of a self-assembled monolayer of thiol chemistry, enabling
the effective immobilization of antibodies.
• These biosensors exhibited exceptional electrochemical performance,
demonstrating consistent and reliable detection of beta-amyloid with
a sensitivity of 0.14 ng mL−1 and outstanding repeatability
• These findings highlight the tremendous potential of the nanopillar-
based immunoelectrochemical biosensor as a robust and promising
platform for point-of-care diagnostics
Modes of Detection of SARS Covid-2 by
Nanobiosensor
Colorimetric assay for SARS-CoV-2 determination
through Antisense oligonucleotides (ASO) N-gene
Quantum dot interaction with the SARS-CoV-2
virus and their utility
 Wearable biosensors
• Managing diabetes, modern continuous glucose monitoring (CGM) devices
provide precise interstitial glucose measurement
• Smartphone apps for health are widely used for self-care and self-
monitoring
• Organic thin film transistors (OTFTs) are the ideal transducers for flexible
and stretchable biosensing because of their softness, inherent function of
amplification, biocompatibility, simplicity of functionalization, low cost, and
diversity of the device
• For lactate and salt detection during physical activity, a novel wearable
electrochemical sweat biosensor using zinc-oxide nanowires (ZnO NWs) has
been introduced
• Monitoring heart functions and warning system -wearable biosensors
 Technology Issues
• Producing Biosensors
 Robust
 Miniaturized
 Low-cost
 Automated
 Easy-to-use biosensors
 Ethical Issues
Patient rights
Informed consent
Confidentiality
Sensor effectiveness
Cost effectiveness
Feminist bioethics
Environmental
Religious
 Regulatory Issues
Laboratory Animal Testing
Long term hazards on lives
Patent
Licensing
Mass production
Commercialization
Thank you for patient listening!

Any QUESTIONS?