Microfluidic devices for Raman spectroscopy and optical trapping

Cell identification is important to differentiate between cells in a sample. In cancer research for example, there is a need for identifying tumor cells and discriminating these from healthy cells. Raman spectroscopy is a non-destructive label-free method that can be used for the analysis of biological or chemical samples by determining the molecular fingerprint of molecules or cells. Traditionally, analyses of biological or chemical samples are done in a specialized lab, with considerable requirements in terms of equipment, time and manual sampling of substances of interest. In the first part of this PhD, we take a step from bulky Raman spectroscopy laboratory analyses towards lab-on-chip (LOC) analyses of sample solutions. The philosophy of LOC research is to reduce the cost and complexity of these laboratory analyses, by miniaturizing and integrating multiple laboratory processes on a single device. Since biomolecules have a low Raman cross-section, these devices should be designed towards maximal collection efficiency and background suppression and hence avoid long acquisition times. We present the modeling, the design and the fabrication process of two microfluidic devices incorporation Raman spectroscopy, from which one enables confocal Raman measurements on-chip. The latter is fabricated using ultra precision diamond tooling and is tested in a proof-of-concept calibration setup, by for example measuring Raman spectra of urea solutions with various concentrations. If one wants to analyze single cells instead of a sample solution, precautions need to be taken. Since Raman scattering is a weak process, the molecular fingerprint of flowing particles would be hard to measure. The low efficiency of Raman scattering can be enhanced using special surface structures, i.e. surface-enhanced Raman spectroscopy but these specialty surfaces are difficult to mass-produce. An alternative method is to stably position the cell under test in the detection area during acquisition of the Raman scattering such that the acquisition time can be increased. Positioning of cells can be done through optical trapping and leads to an enhanced signal-to-noise ratio and thus a more reliable cell identification. Like Raman spectroscopy, optical trapping can also be miniaturized. In the second part of this PhD, we present the modeling and design process of different optical trapping configurations and fabricate a mass-manufacturable polymer microfluidic device for dual fiber optical trapping using two counterpropagating single-mode beams. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we characterize the trapping capabilities of the hot embossed chip. In the third part of this PhD, we combine the optical trapping of particles with the Raman measurement of this trapped particle. This is done by adapting the optofluidic chip designed for Raman spectroscopy in a way it can be used for optical trapping as well. Also in this part, the simulation and design part is shortly presented. The optofluidic chip for combined Raman spectroscopy and optical trapping is finally inserted and characterized in a proof-of-concept demonstration setup. The systems proposed in the first and third part of this PhD research, could be implemented as a reader unit containing external optics in combination with low-cost, mass manufacturable and disposable microfluidic components.