عالية الإنتاجية ميكروفلويديك السريع وانخفاض تكلفة النماذج طرق التعبئة والتغليف
Summary
In this article we describe different techniques for microfluidic rapid prototyping platforms. The proposed techniques are based on ultraviolet (UV) sensitive and temperature curing epoxies, polydimethylsiloxane (PDMS) based tubing, wire-bonding, and anisotropic adhesive films. The assembling procedures presented are developed for both one-time use devices as well as reusable microfluidic systems.
Abstract
In this work, 3 different packaging and assembly techniques are presented. They can be classified into two categories: one-time use and reusable packaging techniques.
The one-time use packaging technique employs UV-based and temperature curing epoxies to connect microtubes to access holes, wire-bonding for integrated circuit connections, and silver epoxy for electrical connections. This method is based on a robust assembly technique that can support relatively high pressure close to 1 psi and does not need any support to strengthen the microfluidic architecture.
Reusable packaging techniques consist of PDMS-based microtube interconnectors and anisotropic adhesive films for electrical connections. These devices are more sensitive and fragile. Consequently, Plexiglas support is added to the microfluidic structure to improve the electrical contact when anisotropic adhesive films are used, and also to strengthen the microfluidic architecture. In addition, a micromanipulator is needed to maintain tubes while using a thin PDMS layer to connect them to the access holes. Different PDMS layer thicknesses, ranging from 0.45-3 mm, are tested to compare the best adherence versus injection rates. Applied injection rates are varied from 50-300 μl/hr for 0.45-3 mm PDMS layers, respectively. These techniques are mainly applicable for low-pressure applications. However, they can be extended for high-pressure ones through plasma-oxygen process to permanently seal the PDMS to glass substrates. The main advantage of this technique, besides the fact that it is reusable, consists of keeping the device observable when the microchannel length is very short (in the range of 3 mm or lower).
Introduction
Recent progresses in microfabrication have led to more complex microfluidic devices including a large number of electrodes and different types of control algorithms. However, these advances highlighted new challenges in packaging. Furthermore, Lab-on-Chip (LoC) is a multidisciplinary concept where microfluidic devices, microelectromechanical systems (MEMS), microelectronic chips among other parts are connected together. Consequently it is impossible to develop a packaging process without considering different constraints of LoC components such as microelectronics circuitry sensitivity and protection, tubing, and mechanical aspects. In addition, packaging the components of a given LoC is closely related to the application1,2. As an example, in optical applications, the transparence of the device is crucial, especially for testing purposes. Thus, it is important to monitor system behavior by keeping the device observable. In applications related to cell or particle manipulations, using low-voltage techniques is more attractive, with the emergence of new microfabrication technologies which facilitate reduced electrode dimensions (from few a micrometers to submicron scale3-5) but considerably increase the number of electrodes to 100 or more.
On the other hand, LoCs dedicated for chemical and biological analysis require long-term observation. Thus, the system packaging and test bench must avoid biological contamination as well as any failure in the electronic devices of LoC in addition to keeping the system observable.
In recently published papers, microfluidic and MEMS are the main parts of a LoC, but other modules may be used for the monitoring of the system. Consequently, testing and validating microfluidic architectures became a challenging issue with the new microfabrication approaches and the high complexity and throughput architectures. Up to now there are no standard testing platforms or supports for microfluidic system, as it is the case for microelectronics dies.
Researchers proposed different packaging techniques for specific uses, such as Xie et al.6 who designed a bio-microfluidic packaging including a microelectronics chip to control DNA separation in microfluidic channels. Beebe et al.7 designed a microfluidic channel with integrated fluid reservoirs and stimuli-responsive hydrogel valves to manipulate fluid samples. Other systems propose the use of electrolytic bubble-based flow sensors to detect pressures through an electrical field to generate air bubbles and measure corresponding pressure8. The sensing system measures the impedance of the bubble and then determines the pressure, which requires special packaging designed to avoid introducing any interference into the measurements. In another work, a room temperature microfluidic packaging method was introduced based on sequential plasma activation process9. Despite the fact that this process could lead to a strongly assembled device, it has limitations when it is used for prototyping purpose or when the device is used several times. The latter may imply frequent replacement of some parts of the system. Moreover, Lee et al. introduced a new packaging technique, called Biolab-on-IC, based on using magnetic fields for individual magnetic bead manipulation, where the microfluidic architecture is designed on the top of the integrated circuit10. In addition, the reliability of packaging and integration of microfluidic systems, considering the system size, optical aspects, and connection parts, are critical issues as detailed by Han and Frazier11. This latter work reflects a typical approach for LoC systems, where several parameters must be precisely fixed and measured during the packaging.
Consequently, microfluidic packaging is a challenging issue for new a generation of microfluidic devices. Packaging includes heterogeneous parts such as tubing, electrical connections and microfluidic support. For tubing, the main issue is the very limited space available to connect the tubes to access the microfluidic holes. The diameter of the current commercially available connectors is in the range of 6 mm; however, the distance between the two access holes is becoming smaller with the reduction of overall system dimensions12-13. Therefore, we have proposed a tubing technique based on PDMS. This tubing process is specially elaborated for the prototyping phase. In fact, owing to the chemical constraint, changing the connection tube after each usage is mandatory to avoid and minimize liquid leakage inside the microstructure and to clean the microchannels. For these purposes, the described process in this paper is particularly applicable for a fast prototyping design.
On the other hand, electrical connections are critical for microfluidic devices that utilize direct or indirect electrical manipulation or measurement. Due to the wide range of microfluidic applications, device dimensions, shape, and number of electrical contacts may vary considerably. Therefore, a versatile method is required, which can be used for different applications. Kaler et al. reported results from their microfluidic rapid prototyping platform, which is based on zero insertion force (ZIF) connectors14. Instead of these later connectors, the presented methods use an anisotropic adhesive conductive film, which can be easily adapted to any shape.
Many researchers do not take into consideration the testing constraints when designing their microfluidic device. In microelectronics, there is many supports used for prototyping purpose and testing, which are called IC holders. These are mainly designed to reduce prototyping and testing times, and offer researchers and engineers an easy way to replace devices in case of failure. Similar to microelectronics, we are also proposing a new testing package for microfluidic devices limited to a 45 mm x 90 mm device size.
Our proposed techniques are targeting to cover a large number of microfluidic devices and applications. These methods can be adapted, extended and upgraded to other applications. We aim to provide one of the first versatile packaging methods for microfluidic devices that are optimized for microfluidic manipulations. For example, one end application for devices packaged with these techniques is separation of polystyrene and carboxyl modified microspheres with artificial cerebrospinal fluid. Nevertheless, they can be used in other applications with different solutions.
In the remainder of this article, three different tubing techniques, 2 electrical connection methods and one microfluidic packaging method are presented and compared.
Protocol
Representative Results
Discussion
The PDMS interconnector is intended for low-pressure applications, liquid leakage into the chip access hole when the PDMS interconnector is subsequently placed on the access hole must be prevented. Therefore, the recommended thickness of PDMS is less than 2 mm. A greater thickness can induce a weak adhesion of the PDMS to the microfluidic chip surface and is not recommended. An unsuccessful trial was made using a thickness of 4 mm. This work focuses on the adherence of the PDMS interconnector to the glass while syringe p…
Disclosures
The authors have nothing to disclose.
Acknowledgements
The authors acknowledge the financial support from NSERC and the Canada Research Chair in Smart Medical Devices, and are grateful for the various tools supplied by CMC Microsystems and ReSMiQ. Thanks are due to Laurent Mouden, for his contributions in this work.
Materials
| Epoxy 731 | Epotek | 731 | |
| PDMS | Dow Corning | SYLGARD 184 | |
| Adhesive conductive film | 3M | ||
| UV Epoxy | Epotek | OG159 | |
| Micropump | Harvard Apparatus | PHD Ultra | |
| PCB | Advanced Circuits | ||
| Plexiglass | Ecole Polytechnique | ||
| Adhesive conductive film | 3M | 9703 | |
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