Ulrik Larsen

Modular concept of a laboratory on a chip for chemical and biochemical analysis

A novel concept of a modular micro chemical analysis system fabricated on silicon wafers using semiconductor technology is presented. The strategy was to design and to develop single fluidic components with specific functions for sample handling, manipulation and measurement. All devices presented are based on monolithic structures manufactured with the same simple microfabrication techniques. The devices are designed to handle particle containing solutions allowing novel applications in biochemical and cytochemical analysis. Components have been developed for chemical analysis such as flow switches for valve-less sample injection and flow guiding, immobilization reactors, dialysis chambers, and filters, and for cell analysis and flow cytometry such as cell sorters and coulter counters. These single fluidic components are freely combinable, which enables the design of analyzers designed for a specific application. Additionally, all fluid components can be equipped with integrated gold electrodes allowing conductivity measurements inside the microchannels. This opens up new application in chemical and biochemical analysis. A few examples in cell diagnostics such as flow cytometry on a chip and in micro flow injection analysis are shown.

Cell Sorting in Microfluidic Systems

Cell sorting has become increasingly important in basic research and medical diagnostics. We demonstrate here that magnetic activated sorting and fluorescent activated sorting can also be envisaged in microfluidic silicon structures. In these structures we take advantage of the laminar flow in microstructures. Paramagnetic particles sheeted by two buffer streams are separated from non-magnetic particles by deflection in a magnetic field gradient. Particles labelled with a fluorochrome are sheeted by two buffer streams, excited and detected by a photo multiplier tube. The photo multiplier tube switches a valve on one of the outlets of the sorter microstructure and selects a particle by forcing it to the collecting outlet. Sorting in these structures is now being optimised with paramagnetic and fluorescent beads, but ultimately it is our intention to sort living cells. One of the major advantages of microfluidic structures is the capability of integrating various functional modules. Simultaneously with optimising our sorter structures, we are investigating various levels of system integration that may improve the performance of the structure. For many cell sorting applications involving biohazardous materials or requiring absolute sterile techniques, a single use microstructure would be advantages. Using silicon processing techniques, metal plating and injection moulding we have produced polymer microfluidic structures. Laminar flow and flow switching have been demonstrated in these polymer microstructures and we are currently investigating their performance in sorting.

Rare Event Cell Surging in a Microfluidic System for Application in Prenatal Diagnosis

A recently developed prototype of a microfluidic cell sorting system fabricated on silicon wafers using semiconductor technology is presented. Preliminary results show that we can successfully sort fluorescent particles from non-fluorescent particles. When the performance of the structure has been optimised we will initiate sorting of fluorescently labelled foetal cells. Sorting foetal cells from mother’s blood offers a safer alternative to currently used methods of prenatal genetic diagnostic screening that carry a substantial risk of harming the foetus and may even lead to pregnancy loss.

Somatic Cell Counting with Silicon Apertures

Counting and sizing of biological cells has been used for half a century as a tool in health care and food quality control. This paper describes the employment of a method known as “Coulter sizing” which is based on a small aperture in a membrane. The possibility of microfabrication of silicon provides a cheap and better alternative to current day technologies of aperture manufacture. Silicon technology allows for the aperture to become cheap enough so it can be used as a disposable unit in a Coulter counter. We have manufactured and investigated silicon apertures with different sizes for sizing and counting of particles. One of the places where a simple particle counter would be applicable is on diary farms, where somatic cell counts (SCC) are used for quality control.

Microtools for cell handling

Microfabrication had a major impact on electronics and is expected to have an equally pronounced effect on chemistry and life sciences. Exploitation of these scientific fields is becoming increasingly dependent on the availability of systems that can perform fast accurate analyses, using minute volumes of sample. By combining microfluidics with micromechanics, microoptics, and microelectronics, systems can be realized that perform complete analyses. The possibility of realize structures with sizes that are in the same range as biological cells makes microtechnology especially interesting for cell analysis. Cell analysis already forms an important, integral part of medical diagnostics and research. Microtechnology provides the opportunity to refine existing cell analysis tools but also allows fabrication of instruments that cannot be realized with conventional technologies. Examples of first steps along this path are provided.

Optimization of Organic Rankine Cycles for Off-Shore Applications

In off-shore oil and gas platform efficiency, the reliability and fuel flexibility are the major concerns when selecting the gas turbine to support the electrical and mechanical demand on the platform. In order to fulfill these requirements, turbine inlet temperature and pressure ratio are not increased up to the optimal values and one or more redundant gas turbines may be employed. With increasing incentives for reducing the CO2 emissions off-shore, improving the thermal efficiency has become a focus area. Due to the peculiar low turbine outlet temperature and due to space and weight constraints, a steam bottoming cycle is not a convenient solution. On the contrary, organic Rankine cycles (ORCs) present the benefits of high simplicity and compactness. Furthermore, the working fluid can be selected considering the temperature profile at which the heat is supplied; hence the heat transfer process and the thermal efficiency of the cycle can be maximized. This paper is aimed at finding the most optimal ORC tailored for off-shore applications using an optimization procedure based on the genetic algorithm. Numerous working fluids are screened through, considering mainly thermal efficiency, but also other characteristics of the fluids, e.g. stability, environmental and human health impacts, and safety issues. Both supercritical and subcritical ORCs are included in the analysis. The optimization procedure is first applied to a conservative ORC where the maximum pressure is limited to 20 bar. Subsequently the optimal working fluid is identified by removing the restriction on the maximum pressure. Different limits on hazards and global warming potential (GWP) are also set. The study is focused on the SGT-500 gas turbine installed on the Draugen platform in the Norwegian Sea. The simulations suggest that, when a high hazard is accepted, cyclohexane is the best solution. With a turbine inlet pressure limit of 20 bar, the combined gas turbine-ORC system presents an efficiency of 43.7%, corresponding to an improvement of 11.9%-points with respect to the gas turbine efficiency. With no upper pressure boundary, cyclohexane at 55.5 bar is the preferable working fluid with a combined thermal efficiency of 44.3%. The supercritical CO2 cycle with a maximum pressure of 192.9 bar is found to be the best alternative if an extremely low hazard is required.

Computer Modeling as a Design Tool for Microfluidic Structures

As the field of microfluidics is maturing, increasingly intricate microsystems are fabricated. This complexity is making the conventional approach of intuitive design of microfluidic structures more difficult or even impossible. In many cases numerous rounds of design, fabrication and testing are required to arrive at microstructures with optimal performance. Computer modeling can significantly shorten this process by suggesting the optimal design on beforehand. The behavior of individual components as well as the interplay between integrated components can be predicted. Here we present the optimization by computer modeling of a microfluidic structure for single step coaxial flow. Experimental characterization of the fluid behavior in the microfluidic structures is presented and compared to predictions from the model.