Optical devices and methods for distributed lab-on-a-chip analyses

Sammanfattning: Lab-on-a-chip (LOC) technologies entail the miniaturization of analytical systems, and the reduction of required sample and reagent volumes. LOC devices offer compact alternatives to classical instrumentation while delivering comparable performance and disposable formats. These aspects make disposable LOC a clear candidate to support distributed chemical sensing applications; however, the need of accessory services and readout obstructs the materialization of pervasively distributed LOC solutions.In this thesis methods and devices to solve this problem are investigated. A distinctive aspect of this work is the pursuit of solutions based on disposable LOC elements specifically conceived to exploit ubiquitous infrastructure for readout and evaluation.Consumer electronic devices, such as cell phones are ubiquitous platforms with residual capabilities that can be used for chemical sensing, if properly interfaced. This work investigates elements and tools needed to empower cell phones as readers of disposable LOC devices and commercial disposable tests.Access to flexible fabrication of LOC devices at low cost is an important requisite for testing ideas and implementing customized solutions. A first contribution in this thesis is the development of a platform for mask less fabrication of 3D microstructures, which coexists on a routine fluorescence microscope. This microscope projection lithography system (MPLS) is capable of controlled 3D micro structuring, including cavities and cantilever geometries, and the sealing of monolithic micro cavities to glass substrates as well as the connection to large scale service areas. This fabrication platform and other fabrication methods were used along this thesis to provide disposable optical and fluidic components.Besides custom-made LOC solutions there are well-established commercial disposable devices, which are essentially compatible with decentralized diagnosis, except for the use of specialized readers that confine them to medical centers. The implementation of high dynamic range (HDR) imaging with standard cell phones, using the phone screen to control exposure, shows that sensitivity and resolution can be boosted to permit robust evaluation of this type of disposable tests, in decentralized scenarios.Solutions employing commercial tests, which have not been designed for cell phone evaluation, are typically suboptimal and the investigation of customized LOC components occupies a central role in this thesis. Accordingly, one important aspect to evaluate LOC devices in compact configurations is to be able to image the LOC at a close distance from the phone camera, a condition for which phones cameras are not able to focus.In addition, different phone brands and models have different optical specifications, and a practical refocusing solution should adapt to all of them. In this work an adaptive lens concept, complemented by phone time-lapse acquisition, which can be integrated in disposable LOCs, is demonstrated.The implementation of sensitive detection methods, such as surface plasmon resonance (SPR), which is compatible with label free protocols that simplify sample conditioning, is central to the materialization of ubiquitous LOCs readable with cell phones. In this thesis a disposable optical coupler, conditioning illumination taken from the phone screen, is used to create an angle resolved SPR signal from a LOC, which is read with the phone front camera. Tested performance is comparable with commercial compact SPR modules and detection of β2 microglobulin, which is an established marker for cancer, inflammatory disorders, and kidney disease, is within the diagnostics range for blood and urine.Finally, fluorescence detection within classical LOC devices is tailored to be detectable with consumer cameras. In this case a disposable optical coupler and fluidics is designed to condition laser illumination into total internal reflection excitation, while DSLR and phone cameras capture optically separated fluorescence. The system configuration supports a broad dynamic range and HDR imaging enables localized resolution boost at selected detection ranges. Detection of free fucose, a diagnostic marker for liver cirrhosis and several cancer forms, is shown feasible with a HDR implementation, as one last example of practical LOC detection schemes for decentralized scenarios.