Advanced Electronics & Sensors

Week 1:
Tutorial 1:

Tutorial 2:

Week 2:
Tutorial 1:
files:
-​ Tutorial 2: Cho et al..pdf
-​ Tutorial 2: Gui et al..pdf
-​ Tutorial 2: Du et al..pdf

Cho et al..pdf:

Electrochemical immunosensor:
-​ Uses antibodies as capture and detection
-​ These antibodies are attached to the Electrode which can be made of various things:
-​ Carbon nanotube:
-​ used as scaffolds: outstanding chemical stability.
-​ Antibody molecules can be immobilized on the CNT-modified electrode.
-​ high sensitivity with selectivity for alpha-amylase, through suppression of
electrical noise.
-​ Graphene:
-​ Honey comb structured.
-​ Has the same intrinsic physical and chemical properties as graphite.
-​ Superior to other carbon allotropes in:
-​ electron transfer speed
-​ increased thermal conductivity
-​ mechanical flexibility -> wider range of applications
-​ biocompatibility
-​ CONS:
-​ Harder to dissolve in water -> has to be modified with hydrophilic
groups, for example the carboxyl group
-​ Indium tin oxide:
-​ Unique optoelectronic properties:
-​ High transmittance
-​ Low cost
 -​ Good electrical conductivity
-​ Can be modified with various chemicals for immobilisation of
antibodies
-​ CONS:
-​ Electron-transfer kinetics is much slower than noble metal and
carbon electrodes.
-​ Nanowire:
-​ PROS:
-​ Small size
-​ High surface to volume ratios
-​ Desirable electronic, optical and magnetic traits
-​ CONS:
-​ Charge on analyte molecule decays exponentially toward zero
with distance
-​ Metallic nanoparticles
-​ Used for:
-​ Increase in efficiency of electron transfer and surface to volume
ratio for the immobilisation of capture antibodies.
-​ CONS:
-​ electrical instability: susceptibility to salt concentrations which may
induce aggregation to be precipitated.

Gui et al..pdf: == Uses Whole-cell biosensors (living cells instead of e.g. DNA) ==

WHAT:
-​ Uses living cells that are genetically modified to react to a target chemical
-​ Which, this reaction will then be converted into a detectable signal like light, colour, or
electricity
-​ It can measure complex biological effects (toxicity, bioavailability), not just chemical
presence

HOW:
1)​ Reporter genes: Create measurable outputs
-​ bioluminescence
-​ light
-​ green fluorescence
-​ colour change
-​ electrochemical change
(each have pros and cons to them ofcourse)
2)​ Host cells: Usually bacteria like [Link] or pseudomonas, though they can also be
mammalian cells
(because they are easy to “extract” from animals like rats? aren’t they more expensive to
‘grow’ than bacteria? idk)
3)​ Regulatory proteins: Detect target molecules and trigger reporter genes
WHY:
-​ It’s: Inexpensive, reusable, real-time, detects bioavailability pollutants (The part that
actually affects living organisms)
-​ Genetically modifiable to detect a wide range of things. (analytes**)
-​ Functional under diverse environmental conditions.

**what you’re trying to measure through chemical reaction

Du et al..pdf: == Uses Nucleic acid-based biosensors ==

WHAT:
Main types of biosensors:
-​ DNA-based biosensors (genosensors)
-​ Detect specific DNA or RNA sequences by hybridisation (base pair
matching)
-​ Used for pathogen or gene detection
-​ WHY: Very specific and useful for medicine, food safety, and
environment.
-​ Aptamer-based biosensors (aptasensors)
-​ Aptamers are synthetic DNA or RNA strands selected to bind a target
-​ Bind to ions, small molecules, proteins, even whole cells
-​ Used for detection of toxins, drug, antibiotics, tumor markers and more
-​ WHY: high specificity, reusable, cheaper than antibodies
-​ DNAzyme-based biosensors
-​ Use catalytic DNA (acts like an enzyme)
-​ Often detect metal ions or small molecules by catalysing colour or
electrical changes
HOW:
-​ Electrochemical:
DNA interacts with target -> Measure electrical signals
-​ Fluorescent:
Light changes when DNA binds or folds into different structures
Fluorescence: Light absorbed by molecule -> causing electrons to jump to higher state
of energy -> they want to go back to the lowest possible state of energy they can
achieve and produce light in the process
-​ Electrochemiluminescent/chemiluminescent:
Light produced by reactions on electrodes (kick out of orbit: apply voltage to an
electrode, the voltage oxidises or reduces the molecules near the surface: kick out of
orbit)
-​ Colorimetric: colour change visible to the eye
-​ SPR/SERS: Optical detection of surface interactions
How SPR works: A thin layer of metal (gold or silver) is illuminated by polarized light at a
specific angle.
At a certain “resonance” angle, electrons on the metal surface (plasmons) oscillate in sync with
the light.​
When molecules (e.g., proteins, DNA, antibodies) bind to the surface, the refractive index at
that surface changes, which shifts the resonance angle.​
The sensor measures this shift — no labels or dyes are needed.
WHY:
-​ Detection of viruses, bacteria, toxins, drugs, antibiotics, and cancer biomarkers.
-​ Can reach extremely low detection limits.
-​ Great promise for point-of-care (POC) diagnostics and environmental monitoring.

Lecture 3

Week 3: we didn't do shit here (very true)

Tutorial 5:
[Link]

Week 4:
Jain et al:
WHAT:
-​ Use of avidin in nanotechnology
-​ Avidin: highly stable tetrameric glycoprotein
-​
HOW:
-​ Target analytes can be bonded to biotin, and as a result, avidin can bond to the
(Joe)-biotin-analyte molecule and a reaction can be read as a result.
WHY:
-​ “Compared to other covalent and non-covalent interactions, the avidin-biotin system
provides enormous advantages such as amplification of weak signals, efficient
operation, high stability and enables the use of highly diluted primary antibodies.”
LIMITATIONS:
-​ “Despite its enormous advantages and wide applicability, avidin has several
limitations, including non-specific binding and possible immunogenicity.”

Applications in nanoscale delivery systems:

-​ Nucleic acid delivery
-​ protein and peptide delivery
-​ Vaccine delivery
-​ Monoclonal antibody delivery
 -​ Small molecule delivery
Applications in diagnosis:
-​ Surface antigen detection
-​ Imaging:
“For diagnostic purposes, the expression of a specific antigen on a particular cell
type can be harnessed and subsequently detected with favorable techniques.[138,
139] Similarly, the types of antigens or markers present on cancer cells reveal the
degrees of malignancy,invasion, neovascularization, and metastasis.”

Pollet et al:

WHAT:
-​ Fiber optic surface plasmon resonance sensor
-​ Detection of change (redshift) in optic cable (because change in refractive index)
HOW:

-​ Optical fibre, gold coating around it, protein repulsive PEG on gold, streptavidin on
PEG, biotin with analyte single strand DNA bonds to streptavidin
-​ With no reaction, light passes into the optical fibre with a specific refractive index
-​ As the target strand bonds to the single strand DNA, it changes the refractive index
of the optical fibre
-​ Causes wavelength of light out to increase (redshift), change in wavelength
correlates to amount of DNA bonded
WHY:
-​ Reusable, cost effective and label free
-​ Piss bart off
-​ 2 factors less expensive than commercially available SPR
-​ Monitor association and dissociation in real time
-​ Low cost os SPR + High sensitivity of added surface chemistry = more accessible for
many other applications.
Vanderyt et al. == Imprinted PDMS - Graphene Oxide Thermal Sensor ==

WHAT:
-​ Surface-imprinted PDMS (polydimethylsiloxane)
-​ With cavities that are shaped like E. coli
-​ Graphene oxide (GO) doped PDMS to improve thermal conductivity
-​ Detection based on heat-transfer changes when bacteria bind to the imprinted
cavities
WHY:
-​ Traditional detection of bacteria is slow, labor intensive, costly
-​ biological receptors are fragile and unstable
-​ Imprinted polymers are stronger, cheap and scalable
-​ PDMS is already widely used and easy to mold
-​ GO improves the thermal sensitivity of the sensor
-​ Allows much lower detection limits
HOW:
-​ Imprinting:
-​ Spin-coat PDMS or PDMS GO on glass or aluminium
-​ Pre-cure at 65°C
-​ Add suspension of E. coli → then the bacteria settle directly onto the soft
PDMS
-​ Finish curing → then wash with SDS → leaves cavities shaped like bacteria
-​ Detection (Heat Transfer Method, or HTM)
-​ Chip mounted on copper heatblock
-​ bacteria solution flows over chip
-​ when E. coli binds into the cavities → thermal resistance increases →
measurable drop in temperature of the flow cell
-​ Addition of GO increases thermal conductivity → bigger temperature
response
-​ Performance:
-​ Limit of detection:
PDMS only: 670 +- 140 CFU/mL
PDMS-GO: 80 +- 10 CFU/mL (~10x improvement)
-​ Impedance spectroscopy is more sensitive, but more complex as well

Wijaya et al. == Review of SPR (Surface plasmon resonance) based biosensors

WHAT:
-​ Imprinting of bio-molecules onto gold surface, changing its refractive index when a
reaction occurs
-​ Detection is based on a change in wavelength/angle of refraction.
-​ Methods of optical excitation of surface plasmons include:
 -​ Prism coupling
-​ Grating coupling
-​ Change in light speed, not the primary direction, but in sideways
directions… changing the angle of the light aka, diffraction
-​ Waveguide coupling

HOW:
-​ Excitation conditions change when the refractive index of the dielectric changes
-​ Biological reactions on a dielectric material can change said refractive index
(Shift in resonance angle)
-​ Can be measured in:
-​ Angular shift
-​ Wavelength shift
-​ Intensity change
-​ Phase change
-​ Surface plasmons are excited by light waves. (in phase-matching conditions)

WHY:
-​ Potential for use in vivo (inside a living organism)
-​ Highly sensitive to refractive index changes
-​ “Silver provides in contrast the sharpest SPR signal and is reported to have
an enhanced sensitivity to thickness and refractive index variation in
comparison to gold.”
-​ Detection of E. coli, serotyping of Salmonella, sensing of living cells

Limitations:
-​ Gold is chemically stable but not ideal as silver has a higher sensitivity, but silver is
unstable.

Applications: (just ideas…)

-​ Medical Diagnostics
-​ Food Safety testing
-​ Cell study

𝓔𝓧𝓐𝓜 𝓣𝓘𝓟𝓢
-​
👅:
Close read in QCM (quartz crystal microbalance)
-​ Imprinting technology (MIPs, and SIPs?)
-​ Blood glucose monitoring (first successful biosensor)
-​ Lateral flow assays (principle of how it works)
-​ Emergence of heat transfer method with DNA (Barts whole jam)
-​ Photonics (will be part of the exam, for sure)
Week 5:
Group 1:
What?
-​ Label-free localized surface plasmon resonance (LSPR)
-​ Monoclonal anti-OTA antibodies immobilized
-​ Direct adsorption
-​ Most common, simplest biofunctionalization strategy
-​ cross-linker functionalization

-​ The optimal Antibodies concentration influences the bioreceptor coverage across

the thin film surface, and thus, the biosensor’s sensitivity.
-​ The greater coverage → greater area for effective OTA binding → stronger LSPR
response → lower detection limit
-​ Surface made of a thin film containing bimetallic Au-Ag nanoparticles embedded in a
Titanium-oxide matrix
-​ limit of detection 7 pg/mL
-​ DSP: basically the bridge between Au-Ag and the OTA
How?
●​ optical-based LSPR transducer
●​ thin film that contains embedded AU-Ag nanoparticles
●​ embedded anti-OTA ab and OTA solutions (max concentration of ota
allowed)
●​ optically monitored both before and after OTA incubation, high sensitivity due to
enhanced plasmonic behaviour of the auag np
-​ Chemical reaction →optical response on the np embedded film
●​ samples on wich sensor was tested was known OTA concentration in white wine

Why?
 -​ Outperforms commercial ELISA techniques
-​ Provides rapid sensitive and selective detection of target analytes by converting
biological reactions into discernable optical signals
-​ Label free: eliminates the need for secondary labels on target molecules→ Simplifies
and reduces possible interference
-​ Thin films are prepared with cost-effective and eco-friendly technique→ easy to scale up
-​ Dynamic range: 0.05 to 2 ng mL^-1 (broad concentration range with low LOD)
-​ High accuracy in complex food matrices
-​

-​ Using this LSPR-based biosensor in microfluidic systems will enable the handling of
smaller volumes and the automation of the analytical process for user-friendly and
portable applications.

Limitations / Challenges:
-​ Orientation and stability of the immobilized Ab
-​ bioreceptor layer reproducibility
-​ Feasibility of a biosensor depends on the food matrix nature, or the pre-treatment
performed. Performance can be affected by the complexity of the food matrix
-​ Non specific binding → blocking of active sites of antibodies
-​ denaturation
-​ conformational alterations (the changes in 3D shape of a molecule in response to
external factors like a change in pH, or temperature, or when interacting with
other molecules)
​ Hindering OTA-antibodies binding affinity
Future work:
-Bioanalytical evolution: volume sample, response time
- Integrating LSPR into microfluids→ Handle smaller volumes and more user friendly and
portable

Group 2:
What?
-PSI material silicon (p-type)

Group 3:
What?
-​ Detection of specific RNA sequences using specific high-sensitivity enzymatic reporter
unlocking (SHERLOCK)
-​ Using CRISPR technology to rapidly identify specific RNA sequences related to diseases
or other genetic issues
 -​ Labelled process, using fluorescent biomarkers as a transducer, transforming a reaction
into visible light which can be detected

How?
-​ CRISPR Cas-13 molecule is used to detect specific RNA sequence
-​ Once RNA sequence is detected, Cas-13 will activate, and start cleaving all nearby RNA
sequences and other molecules, known as collateral cleaving
-​ Inside the system, fluorescent biomarkers will be present, which consist of the
fluorescent molecule and quencher
-​ When bonded together, quencher absorbs all incoming energy, not allowing
fluorescent molecule to release light
-​ Cas-13’s activation will cleave this biomarker, allowing the fluorescent molecule to
release light, indicating the presence of the target RNA sequence

Why?
-​ Very rapid detection of potentially very dangerous RNA sequences (>1 hour, might be
even lower it says somewhere on the paper)
-​ Allows for the use of Cas-13 instead of the commonly used Cas-9 molecule
-​ Can be prepared very quickly as well
-​ But it is not super cost effective due to the need of expensive lab equipment

Week 6:
1st generation:
-​ “their sensor used glucose oxidase (GOx) entrapped over an oxygen electrode by a
semipermeable membrane to select for β-D-glucose in the presence of oxygen gas”
-​ Reaction:
-​ β-D-glucose → β-D-gluconolactone
-​ FAD → FADH2
-​ FADH2 + O2 → FAD + H2O2
-​ H2O2 → 2H+ + O2 + 2e-
-​ 3 electrode system to be able to detect the amount of glucose, not just the presence,
also makes sure that other molecules aren’t oxidised

2nd generation:

Incorporation of a synthetic mediator

-​ This mediator is inside the solution for transportation between the electrode
surface and the enzyme active site.

-​ Direct electron transfer using shuttle molecule

 The mediator (ox) regenerates the FAD, with simultaneous self-reduction.
Then the mediator(RED) regenerated at the electrode surface produces an electric
signal when a low voltage is applied. Which eliminates the background signal from
interfering species.

Ideal mediator:
-​ rapid reaction with reduced enzyme
-​ low solubility in aqueous sample environment
-​ chemically stable in reduced and oxidized forms
-​ nontoxic
-​ have good electrochemical properties

Enzymatic reaction
-​ Glucose reduces the enzyme​
GOx-FAD → GOx-FADH2

Mediator reaction
-​ Mediator oxidizes FADH2
GOx-FADH2 + Mediator(ox) → GOx-FAD + Mediator(red) + 2H+

Electrode reaction
-​ Mediator(red) is oxidized at the electrode
​ Mediator(red) → Mediator(ox) + 2e-

3rd generation: