Autonomous Lab-on-a-chip: solutions and fast prototyping tools

Abstract: In this thesis, solutions for the development of autonomous Lab-on-a-chip (LOC), and 3D printing for fast prototyping of LOC devices are investigated. Lab-on-a-chip devices integrate analytical systems and conditioning processes in a compact package. Small sample volume, disposability, ability to perform complex analysis and performance comparable to classical instrumentation are characteristics that make LOCs excellent candidates for biomedical applications, environmental monitoring and food analysis. Classical LOC configurations usually require additional elements such as pumps, valves, fluidics interface connectors, and even pneumatic control to operate. Also, in most cases, a computer-capable device, or standalone control system, is needed in connection with the measurements. Autonomous LOCs avoid the use of additional components, as they are designed to integrate all necessary parts in one design. Cell phones are the most wide spread computer capable devices, and the advantage to exploit them as analytical instruments is obvious. They have been used in connection with microfluidic LOC measurements, typically using accessory dongles. To connect to the LOCs, in some cases, even permanent modifications of the phones were required. In this thesis, direct coupling to cell phone readout, without accessories beyond the LOC, has been investigated. Autonomous LOC development demands extensive time and resources for prototype optimization. Classical LOC fabrication methods, which are based on lithographic microfabrication, require special equipment and facilities. Additionally, the fabrication of 3D structures require multiple fabrication steps with numerous intermediate alignment. In this thesis, commercial-grade, low-cost 3D printers have been investigated as fast LOC prototyping platforms. The printers (Miicraft® DLP-3D printer and Formlabs Inc. Form+1) are based on Stereo Lithography (SLA). In this additive fabrication technique, a 3D computer model of the LOC is designed. Later, the 3D model is sliced in 2D patterns along the height of the design, and each of the 2D patterns is projected through the printer transparent tank bottom, which contains a liquid photocurable resin. Each exposure cures a thin layer of the resin, and the procedure is repeated adding layer after layer until the 3D printout is completed. With this technique it was possible to obtain real 3D LOC structures with unlimited number of 3D features in one step, within the hour, and at low-cost for prototyping, which constitutes a superb tool for fast and affordable sophistication of LOC architecture. The process was extended in this thesis to another area of complex and costly development: the manufacture of optical components. It was shown that optical components with arbitrary geometry could be obtained within the hour and typically for less than 1€/prototype. The first use of the technique was to produce templates for classical LOCs of polydimethylsiloxane (PDMS) on glass. The procedure was the first, to our knowledge, implemented with consumer grade printers, and included a demonstration of template fabrication for the development of a multilayer PDMS-LOC for colorimetric detection of glucose. The technique then evolved to the complete replacement of the PDMS stage, by conceiving the LOC architecture as a single monolithic printout. This concept was coined Unibody LOC (ULOC) and was used in this thesis for the development of all the autonomous Lab on a Chip solutions. Numerous solutions towards autonomous LOCs were developed such as: multidimensional adaptors that connect for example 1.6mm diameter tubing directly to 50μm wide microfluidic channels, several on plane and multilayer mixers, hybrid ULOC with paper channels, finger-pumps, check-valves, optical couplers and 3D printed optics. Time-dependent optical response bio-chemical reactions were identified as key to implement the link between autonomous LOC with cell phones without other accessories, and relying on ambient light as illumination. Such approach improves the analytical resolution of a colorimetric measurement using essentially the same camera. Finally, all those solutions were integrated to develop a chemical sensing interface for universal cell phone readout, and a 3D printed device for quantitative enzymatic detection using cell phones. 

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