Microfluidics is a multi-disciplinary field of engineering, physics, chemistry, biochemistry, nanotechnology, and biotechnology. By controlling and manipulating liquids at low volume (micro-nano scale), microfluidics has achieved a lot of practical applications such as multiplexing, automation, and high-throughput screening. Lab-on-a-chip (LOC) technology is a concept of integrating several preparative or analytical processes onto a single chip that fits in a human hand. The improvement of LOC technology is intrinsically linked to microfluidics and microtechnology of semiconductors.
Microfluidics has been evolved extremely fast since the contribution of microelectronics in the mid-1950s. Using the photolithography technique in micro-fabrication, the first LOC of gas chromatography was created in 1979 (4). However, the field was still unexplored yet until soft-lithography which adapted microfabrication process for the polymer chips was introduced in the late 80s (5). This solution opened the ability to easily fabricate polymer chips in any lab and offered a wide range of applications in materials, chemistry, and biology as the picture below.
Microfluidics is mainly applied to biotechnology which requires highly sophisticated tools with automated and efficient approaches. One of the greatest achievement is an amplification of DNA strands by massively parallel PCRs (polymerase chain reaction). Other different techniques were succeeded for sequencing DNA, genomics, protein analysis and biorecognition. In the micro-scale, cell study has been developed quickly for the pharmaceutical industry. Those include cellular culture, cellular communication, cell proliferation, migration and stem cell differentiation, specifically in cellular mechanics.
In preparation for those studies, there are many factors that need to be considered and will depend strongly on the types of sample and properties. For instance, cells can be described by intracellular properties (DNA, RNA, and protein molecule interaction) or extracellular physical properties (size, morphology and surface protein expression). In fact, the need for isolation and sorting cells according to different properties of interest is a central component. Researchers have already used a mix of flow-cytometry, magnetic separation, and density-gradient separation but still require newer chip-based technologies to change the field.
In the field of particle and cell sorting, microfluidics can offer accurate and high-throughput methods which are comparable to conventional methods. Those can be classified as either active or passive sorting. An alternative way to categorize the field is fluorescent label-base sorting, bead-based sorting and label-free sorting.
While fluorescence label-based sorting relies on molecular interactions to selectively identify the types of cell, label-free separation based on an inherent physical characteristic of the cell. Such physical markers could be cell size, shape, deformability, density, electrical polarizability, electrical impedance, magnetic susceptibility and hydrodynamic properties.
The work in this thesis is based on Deterministic Lateral Displacement, a passive and label-free sorting. More specifically, two main topics, which focus on the cell sorting, are easy-to-use open DLD for general sorting applications and deformability-based DLD for cancer cells.
More information from my PhD LIC thesis in Lund University:
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