Biosensor Technologies for Cancer Detection

Direct Indirect

 Two large classes of transducers:

• Optical
 Direct Detection (label-free) • Mechanical
o Based on non-catalytic recognition • Field-effect Transistors
o Cell receptors, antibodies, aptamers, etc.
 Indirect Detection
o Based on a catalytic reaction • Fluorescence label
o Require labeled secondary molecule • Electrochemical
o Generally simpler, cheaper, amplifiable
Plasmonic Biosensors

• Surface Plasmon Resonance (SPR)

• Local Surface Plasmon Resonance (LSPR)

SPR-BASED BIOSENSOR
https://www.youtube.com/watch?v=sM-VI3alvAI SPR refresher
 VROMAN EFFECT
VROMAN EFFECT: Competitive adsorption / exchange of proteins

Proteins bind weakly adsorb

first, resulting in protein
displacement

Proteins that bind strongly

adsorb first, resulting in no
protein displacement
 The Vroman Effect and SPR

VROMAN EFFECT: Competitive adsorption / exchange of proteins

(a) Small MW proteins adsorb first, resulting in protein displacement
(b) Large MW proteins adsorb first, resulting in no protein displacement
SPR SETUP
 SPR-BASED BIOSENSOR for Thyroglobulin detection

Tg is injected into both

channels. Tg displaces
The two sensing
IgG in channel 1, while
surfaces are adsorbed
no displacement
by IgG and fibrinogen
occurs in channel 2.

The sensor
produces a
permanent
differential angle
change (Δθ).
SPR-BASED BIOSENSOR for Thyroglobulin detection

Initially the two sensing surfaces are adsorbed by IgG and fibrinogen

Tg is injected into both channels.

Tg displaces IgG in channel 1, while no displacement occurs in channel 2.

The sensor produces a permanent differential angle change (Δθ).

https://www.youtube.com/watch?v=QLT1vrnJXWI Great LSPR video
LSPR: Optical phenomenon generated by plasmons (collective oscillations of the
electron gas in metal nanostructures surrounded by a dielectric).

• When metal nanostructures interact with a light beam, absorption and

scattering of light are enhanced when the plasmon is excited
• Small changes in the dielectric environment around the nanostructures cause
extremely intense and confined electromagnetic fields induced by the LSPR
• Detected by optical spectroscopy (extinction measurements for large
amounts of nanoparticles, e.g. colloids, and scattering measurements for low
densities of nanoparticles, e.g. particles on a surface).
• Two types of LSPR:
– #1) Aggregation sensors: when two particles come together (e.g. upon biorecognition
binding), near-field electromagnetic coupling causes drastic color changes that can be
observed with the “naked eye”

Storhoff et al.,
Homogeneous detection of
unamplified genomic DNA
sequences based on
colorimetric scatter of gold
nanoparticle probes,
Nature Biotechnol 22: 883
(2004)
• Two types of LSPR:

– #2) Refractive index sensors: Local changes in the refractive index (e.g. upon binding of a
biomolecule on the surface of the nanostructure) cause a shift in the LSPR peak
• Many shapes can be fabricated (in bulk or by nanofabrication techniques),
obtaining various spectral shifts:
Caldwell et al., Large-area plasmonic hot-spot
arrays: sub-2 nm interparticle separations with
plasma-enhanced atomic layer deposition of Ag on
periodic arrays of Si nanopillars, Optics Express 19:
26056 (2011)

Larsson et al., Sensing characteristics of NIR

Localized Surface Plasmon Resonances in Gold
Nanorings for Application as Ultrasensitive
Biosensors, NanoLetters 7: 1256 (2007)
Mayer et al., A label-free immunoassay based upon localized surface plasmon
resonance of gold nanorods, ACS Nano 2: 687 (2008)
 14 nm

Choi and Semancik, Multi-resonant plasmonic

nanodome arrays for label-free biosensing
applications, Nanoscale 2: 8138 (2013)

• Fabricated in plastic by nanoreplica molding

• Avoids high-resolution lithography
• The array acts as a diffraction grating that
produces multiple scattering by periodically-
spaced nanodome features
• The resonant electrical field density at the 14
nm gap between the nanodomes is very
sensitive to adsorbates
Lassiter et al., Plasmonic waveguide modes of film-coupled metallic nanocubes,
NanoLetters 13: 5866 (2013)
• The cube geometry coupled with the molecular spacer layer (g) to define the gap
between the nanocube and the metal film provides a robust method to define
the experimentally control a plasmonic junction with extreme precision
Gartia et al., Colorimetric Plasmon Resonance Imaging Using Nano Lycurgus Cup Arrays,
Advanced Optical Materials 1: 68 (2013)