Chapter 9 – Emerging Biophysics Techniques  417

accelerate a more tailored treatment at far earlier stages in these chronic conditions that has

been available previously.

9.4.1  LAB-​ON-​A-​CHIP AND OTHER NEW DIAGNOSTIC TOOLS

Developments in microfluidics and surface chemistry conjugation methods (see

Chapter 7), photonics, micro-​ and bioelectronics, and synthetic biology have all facilitated

the miniaturization and increased portability of smart biosensing devices. These devices

are designed to detect specific features in biological samples, for example, the presence

of particular types of cells and/​or molecules. In doing so, this presents a diagnostic and

high-​throughput screening capability reduced to a very small length scale device, hence

the phrase lab-​on-​a-​chip. An ultimate aim is to develop systems in which diagnosis can be

made by the detection and analysis of microliter quantities of a patient specimen, such as

blood, sputum, urine, fed through a miniaturized biomolecular detection device coupled

to smart microelectronics.

Typically, these devices consist of hybrid nonbiological solid-​state silicon-​based substrates

with synthetic arrangements of biological matter, in a complex microchip arrangement that

often employs controlled microfluidics to convey biological sample material in aqueous solu­

tion to one or more detection zones in the microchip. For specific detection of biomarkers, that

is, labels that are specific to certain biomolecules or cell types, a surface pull-​down approach

is typical. Here, the surface of a detection zone is coated with a chemical rearrangement that

binds specifically to one or more biomarkers in question (see Chapter 7). Once immobilized,

the biological material can then be subjected to a range of biophysical measurements to

detect its presence. These are all techniques that have been discussed in the previous chapters

of this book.

Fluorescence detection can be applied if the biomarker can be fluorescently labeled. To

achieve fluorescence excitation, devices can utilize the photonics properties of the silicon-​

based flow-​cell substrate, for example, photonic waveguiding to enable excitation light to

be guided to the detection zone, photonic bandgap filtering to separate excitation light from

fluorescence emissions, and smart designs of microfabricated photonic surface geometries to

generate evanescent excitation fields to increase the detection signal-​to-​noise ratio by min­

imizing signal detection from unbound biological material.

Nonfluorescence detection lab-​on-​a-​chip biosensors are also being developed. These

include detection metrics based on laser dark-​field detection of nanogold particles, and

label-​free approaches such as evanescent field interferometry, surface plasmon resonance–​

type methods and Raman spectroscopy, and surface-​enhanced Raman spectroscopy (see

Chapter 3), also, using electrical impedance and ultrasensitive microscale quartz crystal

microbalance resonators (see Chapter 6). Microcantilevers, similar to those used in AFM

imaging (see Chapter 6), can similarly be used for biomolecule detection. Here, the surface

of the microcantilever is chemically functionalized typically using a specific antibody. As

biomolecules with specificity to the antibody bind to the cantilever surface, this equates to

a small change in effective mass, resulting in a slight decrease in resonance frequency that

can be detected. Typical microcantilevers have a resonance frequency of a few hundred kHz,

with an associated quality factor (or Q factor) of typically 800–​900. For any general resonator

system, Q is defined as

Q = ^v

v

0

∆

where

v0 is the resonance frequency

Δv is the half-​power bandwidth, which is thus ~1 kHz