Design automation based on fluid dynamics

This article was accepted and presented at the 9th International Workshop on Bio-Design Automation, Pittsburgh, Pennsylvania (2017).Microfluidic devices provide researchers with numerous advantages such as high throughput, increased sensitivity and accuracy, lower cost, and reduced reaction time. However, design, fabrication, and running a microfluidic device are still heavily reliant on expertise. Recent studies suggest micro-milling can be a semi-automatic, inexpensive, and simple alternative to common fabrication methods. Micro-milling does not require a clean-room, mask aligner, spin-coater, and Plasma bonder, thus cutting down the cost and time of fabrication significantly. Moreover, through this protocol researchers can easily fabricate microfluidic devices in an automated fashion eschewing levels of expertise required for typical fabrication methods, such as photolithography, soft-lithography, and etching. However, designing a microfluidic chip that meets a certain set of requirements is still heavily dependent on a microfluidic expert, several days of simulation, and numerous experiments to reach the required performance. To address this, studies have reported random automated design of microfluidic devices based on numerical simulations for micro-mixing. However, random design generation is heavily reliant on time-consuming simulations carried out beforehand, and is prone to error due to the accuracy limitations of the numerical method. On the other hand, by using micro-milling for ultra-fast and inexpensive fabrication of microfluidic devices and Taguchi design of experiments for state-space exploration of all of the geometric parameters, we are able to generate a database of geometries, flow rates, and flow properties required for a single primitive to carry out a specified microfluidic task

Microfluidic Platform for Adherent Single Cell High-Throughput Screening

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Traditionally, in vitro investigations on biology and physiology of cells rely on averaging the responses eliciting from heterogeneous cell populations, thus being unsuitable for assessing individual cell behaviors in response to external stimulations. In the last years, great interest has thus been focused on single cell analysis and screening, which represents a promising tool aiming at pursuing the direct and deterministic control over cause-effect relationships guiding cell behavior. In this regard, a high-throughput microfluidic platform for trapping and culturing adherent single cells was presented. A single cell trapping mechanism was implemented based on dynamic variation of fluidic resistances. A round-shaped culture chamber (Φ=250μm, h=25μm) was conceived presenting two connections with a main fluidic path: (i) an upper wide opening, and (ii) a bottom trapping junction which modulates the hydraulic resistance. Several layouts of the chamber were designed and computationally validated for the optimization of the single cell trapping efficacy. The optimized chamber layouts were integrated in a polydimethylsiloxane (PDMS) microfluidic platform presenting two main functionalities: (i) 288 chambers for trapping single cells, and (ii) a chaoticmixer based serial dilution generator for delivering both soluble factors and non-diffusive molecules under spatio-temporally controlled chemical patterns. The devices were experimentally validated and allowed for trapping individual U87-MG (human glioblastoma-astrocytoma epithelial-like) cells and culturing them up to 3 days

Testing microelectronic biofluidic systems

According to the 2005 International Technology Roadmap for Semiconductors, the integration of emerging nondigital CMOS technologies will require radically different test methods, posing a major challenge for designers and test engineers. One such technology is microelectronic fluidic (MEF) arrays, which have rapidly gained importance in many biological, pharmaceutical, and industrial applications. The advantages of these systems, such as operation speed, use of very small amounts of liquid, on-board droplet detection, signal conditioning, and vast digital signal processing, make them very promising. However, testable design of these devices in a mass-production environment is still in its infancy, hampering their low-cost introduction to the market. This article describes analog and digital MEF design and testing method

Synthetic biology and microdevices : a powerful combination

Recent developments demonstrate that the combination of microbiology with micro-and nanoelectronics is a successful approach to develop new miniaturized sensing devices and other technologies. In the last decade, there has been a shift from the optimization of the abiotic components, for example, the chip, to the improvement of the processing capabilities of cells through genetic engineering. The synthetic biology approach will not only give rise to systems with new functionalities, but will also improve the robustness and speed of their response towards applied signals. To this end, the development of new genetic circuits has to be guided by computational design methods that enable to tune and optimize the circuit response. As the successful design of genetic circuits is highly dependent on the quality and reliability of its composing elements, intense characterization of standard biological parts will be crucial for an efficient rational design process in the development of new genetic circuits. Microengineered devices can thereby offer a new analytical approach for the study of complex biological parts and systems. By summarizing the recent techniques in creating new synthetic circuits and in integrating biology with microdevices, this review aims at emphasizing the power of combining synthetic biology with microfluidics and microelectronics

Development and deployment of a microfluidic platform for water quality monitoring

There is an increasing demand for autonomous sensor devices which can provide reliable data on key water quality parameters at a higher temporal and geographical resolution than is achievable using current approaches to sampling and monitoring. Microfluidic technology, in combination with rapid and on-going developments in the area of wireless communications, has significant potential to address this demand due to a number of advantageous features which allow the development of compact, low-cost and low-powered analytical devices. Here we report on the development of a microfluidic platform for water quality monitoring. This system has been successfully applied to in-situ monitoring of phosphate in environmental and wastewater monitoring applications. We describe a number of the technical and practical issues encountered and addressed during these deployments and summarise the current status of the technology

Development of flow focusing device for the visualization of leukocyte rolling adhesion

La microfluídica es un área de la microtecnología basada en chips de PDMS que está siendo utilizada cada vez más en multitud de aplicaciones. Una de estas aplicaciones es la investigación biomédica. La microfluídica o “Lab on a Chip” se ha convertido en una manera de realizar experimentos biomédicos y diagnósticos de una manera barata, rápida y eficaz. Cuando se realizan estudios sobre la extravasación leucocitaria utilizando chips microfluídicos, podemos observar la inconsistencia en la trayectoria de rodadura de los leucocitos debido a un flujo laminar. En este trabajo de fin de grado presentamos un método para centrar la interfaz de células en el centro de canal microfluídico. Cuando las células circulan por los sistemas microfluídicos, las células tienden a circular de manera aleatoria por los canales. Por tanto, con el sistema propuesto en este trabajo, dichas células serán redirigidas a la porción central del canal con el fin de recrear el fenómeno de rodadura presente en nuestro sistema circulatorio y así obtener información más detallada. Los resultados de este trabajo muestran la utilidad y la versatilidad de este dispositivo para experimentos relacionados

A droplet routing technique for fault-tolerant digital microfluidic devices

Abstract—Efficient droplet routing is one of the key approaches for realizing fault-tolerant microfluidic biochips. It requires that run-time diagnosis and fault recovery can be made possible in such systems. This paper describes a droplet routing technique for a fault-tolerant digital microfluidic platform. This technique features handling of many microfluidic operations simultaneously and uses on-chip sensors for diagnosis at run-time.\ud Once a fault is detected during the droplet routing, recovery procedures will be started-up immediately. Faulty units on the chip will be marked and isolated from the array so that the remaining droplets can still be routed along a fault-free path to their destinations. This method guarantees a non-stop fault-tolerant operation for very large microfluidic arrays.\u

A Microfluidic Platform for Precision Small-volume Sample Processing and Its Use to Size Separate Biological Particles with an Acoustic Microdevice.

A major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15-1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection, system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing

Current commercialization status of electrowetting-on-dielectric (EWOD) digital microfluidics.

The emergence of electrowetting-on-dielectric (EWOD) in the early 2000s made the once-obscure electrowetting phenomenon practical and led to numerous activities over the last two decades. As an eloquent microscale liquid handling technology that gave birth to digital microfluidics, EWOD has served as the basis for many commercial products over two major application areas: optical, such as liquid lenses and reflective displays, and biomedical, such as DNA library preparation and molecular diagnostics. A number of research or start-up companies (e.g., Phillips Research, Varioptic, Liquavista, and Advanced Liquid Logic) led the early commercialization efforts and eventually attracted major companies from various industry sectors (e.g., Corning, Amazon, and Illumina). Although not all of the pioneering products became an instant success, the persistent growth of liquid lenses and the recent FDA approvals of biomedical analyzers proved that EWOD is a powerful tool that deserves a wider recognition and more aggressive exploration. This review presents the history around major EWOD products that hit the market to show their winding paths to commercialization and summarizes the current state of product development to peek into the future. In providing the readers with a big picture of commercializing EWOD and digital microfluidics technology, our goal is to inspire further research exploration and new entrepreneurial adventures