Configurable and Up-Scalable Microfluidic Life Science Platform for Cell Based Assays by Gravity Driven Sequential Perfusion and Diffusion

Microfluidics has the potential to significantly change the way modern biology is performed, but for this potential to be realized several on-chip integration and operation challenges have to be addressed. Critical issues are addressed in this work by first demonstrating an integrated microfluidic tmRNA purification and real time nucleic acid sequence based amplification (NASBA) device. The device is manufactured using soft lithography and a unique silica bead immobilization method for the nucleic acid micro purification column. The integrated device produced a pathogen-specific response in < 3 min from the chip-purified RNA. Further enhancements in the device design and operation that allow the on-chip integration of mammalian cell handling and culturing produced a novel integrated NASBA array. This system demonstrated for the first time that it is possible to combine on a single micro-device cell culture and real time NASBA. In order to expand the cell based assay capabilities of the integrated NASBA array and simplify the device operation novel hydrodynamics and cell sedimentation within trench structures and gravity driven sequential perfusion and diffusion mechanisms were developed. These mechanisms were characterized and implemented within an iCell array device. iCell array can completely integrate cell based assays with bio-analytical read-out. The device is highly scalable and can enable the configurable on-chip integration of procedures such as adherent and non-adherent cell-culture, cellstimulation, cell-lysis, cell-fixing, protein-immunoassays, bright field and fluorescent microscopic monitoring, and real time detection of nucleic acid amplification. The device uses on-board gravity driven flow control which makes it simple and economical to operate with dilute samples (down to 5 cells per reaction), low reagent volumes (50 nL per reaction), highly efficient cell capture (100% capture rates) and single cell protein and gene expression sensitivity. The key results from this work demonstrate a novel technology for versatile, fully integrated microfluidic array platforms. By multiplexing this integrated functionality, the device can be used from routine applications in a biology laboratory to high content screenings

Overview of Materials for Microfluidic Applications

For each material dedicated to microfluidic applications, inherent microfabrication and specific physico‐chemical properties are key concerns and play a dominating role in further microfluidic operability. From the first generation of inorganic glass, silicon and ceramics microfluidic devices materials, to diversely competitive polymers alternatives such as soft and rigid thermoset and thermoplastics materials, to finally various paper, biodegradable and hydrogel materials; this chapter will review their advantages and drawbacks regarding their microfabrication perspectives at both research and industrial scale. The chapter will also address, the evolution of the materials used for fabricating microfluidic chips, and will discuss the application‐oriented pros and cons regarding especially their critical strategies and properties for devices assembly and biocompatibility, as well their potential for downstream biochemical surface modification are presented

Microfabrication and Applications of Opto-Microfluidic Sensors

A review of research activities on opto-microfluidic sensors carried out by the research groups in Canada is presented. After a brief introduction of this exciting research field, detailed discussion is focused on different techniques for the fabrication of opto-microfluidic sensors, and various applications of these devices for bioanalysis, chemical detection, and optical measurement. Our current research on femtosecond laser microfabrication of optofluidic devices is introduced and some experimental results are elaborated. The research on opto-microfluidics provides highly sensitive opto-microfluidic sensors for practical applications with significant advantages of portability, efficiency, sensitivity, versatility, and low cost

A Monolithically-Integrated μGC Chemical Sensor System

Gas chromatography (GC) is used for organic and inorganic gas detection with a range of applications including screening for chemical warfare agents (CWA), breath analysis for diagnostics or law enforcement purposes, and air pollutants/indoor air quality monitoring of homes and commercial buildings. A field-portable, light weight, low power, rapid response, micro-gas chromatography (μGC) system is essential for such applications. We describe the design, fabrication and packaging of μGC on monolithically-integrated Si dies, comprised of a preconcentrator (PC), μGC column, detector and coatings for each of these components. An important feature of our system is that the same mechanical micro resonator design is used for the PC and detector. We demonstrate system performance by detecting four different CWA simulants within 2 min. We present theoretical analyses for cost/power comparisons of monolithic versus hybrid μGC systems. We discuss thermal isolation in monolithic systems to improve overall performance. Our monolithically-integrated μGC, relative to its hybrid cousin, will afford equal or slightly lower cost, a footprint that is 1/2 to 1/3 the size and an improved resolution of 4 to 25%