Applications of microfluidic chips in optical manipulation & photoporation
Abstract
Integration and miniaturisation in electronics has undoubtedly revolutionised the
modern world. In biotechnology, emerging lab-on-a-chip (LOC) methodologies promise all-integrated laboratory processes, to perform complete biochemical or medical
synthesis and analysis encapsulated on small microchips. The integration of electrical, optical and physical sensors, and control devices, with fluid handling, is creating
a new class of functional chip-based systems. Scaled down onto a chip, reagent and
sample consumption is reduced, point-of-care or in-the-field usage is enabled through
portability, costs are reduced, automation increases the ease of use, and favourable
scaling laws can be exploited, such as improved fluid control. The capacity to manipulate single cells on-chip has applications across the life sciences, in biotechnology,
pharmacology, medical diagnostics and drug discovery.
This thesis explores multiple applications of optical manipulation within microfluidic chips. Used in combination with microfluidic systems, optics adds powerful
functionalities to emerging LOC technologies. These include particle management
such as immobilising, sorting, concentrating, and transportation of cell-sized objects,
along with sensing, spectroscopic interrogation, and cell treatment.
The work in this thesis brings several key applications of optical techniques
for manipulating and porating cell-sized microscopic particles to within microfluidic
chips. The fields of optical trapping, optical tweezers and optical sorting are reviewed
in the context of lab-on-a-chip application, and the physics of the laminar fluid flow
exhibited at this size scale is detailed. Microfluidic chip fabrication methods are
presented, including a robust method for the introduction of optical fibres for laser
beam delivery, which is demonstrated in a dual-beam optical trap chip and in optical
chromatography using photonic crystal fibre. The use of a total internal reflection microscope objective lens is utilised in a
novel demonstration of propelling particles within fluid flow. The size and refractive
index dependency is modelled and experimentally characterised, before presenting
continuous passive optical sorting of microparticles based on these intrinsic optical
properties, in a microfluidic chip.
Finally, a microfluidic system is utilised in the delivery of mammalian cells to a
focused femtosecond laser beam for continuous, high throughput photoporation. The
optical injection efficiency of inserting a fluorescent dye is determined and the cell
viability is evaluated. This could form the basis for ultra-high throughput, efficient
transfection of cells, with the advantages of single cell treatment and unrivalled
viability using this optical technique.
Type
Thesis, PhD Doctor of Philosophy
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