Open Microfluidics

By Jean Berthier, Kenneth A. Brakke and Erwin Berthier

Open microfluidics or open-surface is becoming fundamental in scientific domains such as biotechnology, biology and space. First, such systems and devices based on open microfluidics make use of capillary forces to move fluids, without any need for external energy. Second, the “openness” of the flow facilitates the accessibility to the liquid in biotechnology and biology, and reduces the weight in space applications.

This book has been conceived to give the reader the fundamental basis of open microfluidics. It covers successively

• The theory of spontaneous capillary flow, with the general conditions for spontaneous capillary flow, and the dynamic aspects of such flows.
• The formation of capillary filaments which are associated to small contact angles and sharp grooves.
• The study of capillary flow in open rectangular, pseudo-rectangular and trapezoidal open microchannels.
• The dynamics of open capillary flows in grooves with a focus on capillary resistors. The case of very viscous liquids is analyzed.
• An analysis of suspended capillary flows: such flows move in suspended channels devoid of top cover and bottom plate. Their accessibility is reinforced, and such systems are becoming fundamental in biology.
• An analysis of “rails” microfluidics, which are flows that move in channels devoid of side walls. This geometry has the advantage to be compatible with capillary networks, which are now of great interest in biotechnology, for molecular detection for example.
• Paper-based microfluidics where liquids wick flat paper matrix. Applications concern bioassays such as point of care devices (POC).
• Thread-based microfluidics is a new domain of investigation. It is seeing presently many new developments in the domain of separation and filtration, and opens the way to smart bandages and tissue engineering.

 

The book is intended to cover the theoretical aspects of open microfluidics, experimental approaches, and examples of application.

• Language: English
• Publisher: Wiley
• Release date: Jul 20, 2016
• ISBN: 9781118720820

Book preview

Introduction

Open Microfluidics

Microfluidics is a relatively new scientific domain. Nevertheless its evolution has been extremely fast. Even if solutions for microelectronics [1-4] and outer space [5-8] have contributed to the development of microfluidics since the mid-1950s, it is now mainly biotechnology that boosts microfluidics and contributes to making it a growing scientific domain.

The goal of biotechnology is the fabrication of highly sophisticated tools to assist biologists in their research, automate and increase the efficiency of biology and medicine, and furnish solutions for the discovery of new drugs in pharmacology. At its beginning, biotechnology followed an engineering approach, due to the necessary physical development of the techniques. Progressively it has shifted to a biology-oriented field, in order to be closer to the needs of biology and medicine. [9].

These tools have first targeted with success genomics and DNA recognition. For example, many different solutions for sequencing DNA and biorecognition have been developed [10-14]. Amplification of DNA strands by massively parallel PCRs (polymerase chain reaction) is probably one of the greatest achievements of biotechnology [15-17]. Then, owing to its immense potentialities, biotechnology extended its applications to protein analysis [19] and cell studies [19-24]. In particular, cell study, which includes cellular culture, cellular communication, cell migration, stem cell differentiation, cellular mechanics, etc., is now of utmost importance for the pharmaceutical industry [25-27].

Because biological targets are nearly always immersed in liquids, biotechnology heavily relies on microfluidics. However, the particularity of microfluidics for biotechnology is that it is seldom a stand-alone field. Microfluidic solutions for biotechnology most of the time require a multiphase approach (figure 1).

Figure 1 Biotechnology is a composite science in which microfluidics is a fundamental subdomain.

Biology, material science and chemistry are closely linked to the achievements of biotechnological systems. Clearly, systems for biology require adequate microfluidics to transport, concentrate, and sort the biochemical targets or the biologic objects. They need adapted materials, whose microfabrication is not too complicated and not too expensive, and the required chemical species and reagents for the completion of the biological processes. A good biotechnological solution is like a puzzle that incorporates compatible and adapted sub-solutions in each of these subdomains. Due to the evolution of biotechnology, different microfluidic solutions have been successively developed, which are shown in figure 2.

Figure 2 The main categories of microfluidics and their applications. Inertial microfluidics [97], reprinted with permission ©2008 ACS; paper-based microfluidics, reprinted with permission by Albert Folch, University of Washington, and from [96], reprinted with permission ©2011 ACS; rail based microfluidics [93], reprinted with permission ©2005 ACS; suspended microfluidics [74], reprinted with permission ©2013 PNAS; digital microfluidics, two phase flows and encapsulation, courtesy CEA-Leti; emulsion [38], reprinted with permission ©2003 AIP.

The first microfluidic solutions were based on closed or confined microflows. The fluidic network is a transposition to the microscale of conventional flow systems. These microfluidic solutions, usually called Lab-on-a-Chip (LOC), have the great advantage of using smaller volumes of samples and costly reagents than macroscale devices. Also, their sensitivity is higher, and operating time much shorter, due to the reduced dimensions of such systems. These flows are driven by pumps or syringes external to the chip itself and many different types of valves have been developed [28-30]. These devices are mostly used in laboratories, owing to the need of auxiliary external systems, such as pumps, multiple syringes systems, reservoirs, etc. Systems based on closed microfluidics have had great success and accomplished many important achievements, such as massively parallel DNA amplification [31,32], and the study of stem cell behavior [33-35].

In order to further reduce sample and reagent volumes, it was found that droplets could be used as vessels to perform the desired processes. The term droplet microfluidics is used to characterize such systems. The volumes used in such systems can be very small, on the order of a few nanoliters. Two different approaches depending on the targeted applications have been followed: first, a two-phase approach where the sample and reagents (usually aqueous liquids) are transported by an immiscible fluid (usually an organic liquid, such as mineral oil) in a larger network [36-40]. Second, a digital microfluidic approach, where droplets are moved one by one or in parallel on a patterned substrate by electrical (electrowetting and EWOD) or acoustic (SAW) methods [41-45].

Recently, the need for portable systems has appeared. This need is linked to the development of point-of-care (POC) and home-care medicine, where user-friendly, portable, and low-cost systems can be used at the doctor’s office or directly by the patients themselves to monitor their health, or detect bacteria and viruses from a blood prick [46-50]. Contrary to the conventional microfluidic solutions presented above, the requirement for portability and low cost is associated to the development of passive or nearly passive solutions, where external auxiliary systems are absent, except perhaps the energy of a mobile phone or a compact transportable energy source. Obviously, capillarity is the solution for moving liquids under these conditions [51]. In a capillary solution, the energy required for the motion of the fluids is the surface energy of the walls, which is built in at the moment of fabrication, or by appropriate functionalization of the walls [46,52].

Such portable systems arewell-adapted, for example, to blood monitoring [53,54]. Human blood contains a bounty of information on human health: from the numerous metabolites contained in the plasma, such as glucose, cholesterol, and thyroidal hormones, to the bacteria and viruses transported by blood cells, and circulating tumor cells characteristics of cancerous attack [55-58]. Moreover, cell count, coagulation time, hemoglobin and fibrinogen levels are of great importance for health monitoring [59,60].

Capillary flow in cylindrical tubes was first studied by Bell, Cameron, Lucas, Washburn and Rideal in the 1910s [61-64]. With the development of new biological solutions for point-of-care and home care systems, studies on capillary flows have seen a revival. The first capillary systems to have been developed are fully closed rectangular channels; new functionalities such as trigger valves and capillary pumps have been invented to enhance the potentialities of such devices [65-66].

Still more recently, it became apparent that direct accessibility to biological systems would be a great advantage [67]. Open systems, i.e. microfluidic systems with open boundaries, bring the advantages of accessibility: Addition of reagents, pipetting for the addition or retrieval of biologic liquids or objects, and human interventions on the system can then all be easily performed [52]. Also, optical observation is facilitated. Finally, these systems have the ability to eliminate air bubbles, which are a serious drawback in many closed systems. All these aspects contribute to making open capillary systems an interesting choice for POC and home-care systems, under the condition that the limit of detection (LOD) and scalability are sufficient.

Let us cite the arguments of BioProbe [68]:

Probing biological systems locally in an open space can lead to new insight and breakthroughs. Living matter likes surfaces. Substrates that are functionalized for biological applications are increasingly used and also commercially available. Microfluidics should be able to interact with such substrates in the open space, essentially in their native state, which will facilitate the study of biological samples. To succeed in these endeavors, microfluidics needs to eliminate one of their major constraints: the walls.

These arguments have led to the development of capillary systems where some boundaries are open, i.e. in contact with the surrounding air. The names of open microfluidics, or open-surface microfluidics, or open-space microfluidics have emerged.

In fact, the domain of open microfluidics covers many different situations. Open capillarity has many different aspects, from the propagation of capillary filaments in corners [5,6,69-71], to the spontaneous capillary flow in open U and V-grooves [71-73], to suspended capillary flows [74,75], and to paper-based and thread-based microfluidics [76-80]. A panel of the different open-surface microfluidic configurations is shown in figure 3. In this book, electrowetting, capillary self-alignment and capillary rise are not treated extensively, as they are already widely documented in the literature [81,82].

Figure 3 The main categories of microfluidics and their applications.

The first chapter of this book is dedicated to the theoretical approach to spontaneous capillary flow (SCF). Using the Gibbs free energy [83], it is shown that the condition to obtain SCF in an open or closed, composite or not, flow channel is that the equivalent Cassie angle defined in a cross-section is less than 90° It demonstrates that SCF occurrence depends only on the geometry and the contact angles [84]. Next, the dynamics of capillary flows are presented. It is shown that, except for a very small length at the channel entrance where inertial effects appear [85], the viscous regime defined by the Lucas-Washburn-Rideal (LWR) model can be transposed to arbitrary cross-sectional channels, if precautions are taken [62-64,86]. Finally, the question of the dynamic contact angle is investigated. It is shown that an advancing contact angle only concerns essentially the entrance to the capillary channel [87-89].

The second chapter presents an oft-encountered feature in modern capillary microsystems: capillary filaments. The physics of these filaments was first investigated by Concus and Finn [5,6] in the context of spacecraft studies. These filaments may form in sharp corners or in cracks, and can extend endlessly as long as there is liquid available [82]. In capillary systems, these filaments may flow alone, or with the bulk of the liquid [69-71]. The different flow regimes in rectangular open channels are presented. Next, it is shown that the SCF condition in sharp V-grooves, deduced from the theory of the preceding chapter, reduces to the Concus-Finn condition [73,84]. Finally, the formation of filaments in different geometries is theoretically and numerically investigated.

Rectangular, open microchannels, for simplicity called U-grooves in this book, are probably the most common open microfluidic devices, due to their easy fabrication. It suffices to mill a plastic plate to obtain such channels. The study of spontaneous capillary flow in such channels is the subject of chapters 3 and 4. In chapter 3, the conditions for SCF in the geometry of U-grooves are presented. Different geometries are investigated: straight, turning U-grooves, and U-grooves of varying cross-section (figure 4).

Figure 4 Different geometries of U-grooves. A: SCF passing through multiple cylindrical chambers, from an inlet port (right) to an outlet port (left); B: parallel SCFs from an inlet port to multiple outlet ports; C: multiple microgrooves in parallel; D: winding U-groove with cylindrical wells; E: SCF filling of a cylindrical cavity; F: Concus-Finn filaments in an open cylinder; G: Concus-Finn filaments in a varying cross-section U-groove. Photographs: J. Berthier, N. Villard, D. Gosselin (CEA-Leti).

In chapter 4, dynamical considerations on the capillary flow in U-grooves are presented [72,90,91]. The concept of flow resistor is developed. It is shown that the concepts of trigger valves, capillary pumps, and flow resistor, transposed from closed capillary systems [65,66] to open channels, may still be valid if precautions are taken.

Suspended microfluidics has very recently appeared in the literature [74,75,92]. It is the subject of chapter 5. By definition, suspended microflows are flows in channels devoid of ceilings and floors. Spontaneous flow conditions for different types of suspended microflows are given. Suspended microfluidics brings additional accessibility to open biotechnological systems, and is the source of new applications. Especially, applications to suspended flows of liquid polymers are presented.

Chapter 6 presents new developments for rail-based microflows [93]. Rail-based microfluidics is, in principle, similar to suspended microfluidics. In such systems, the liquid flows between two horizontal rails, top and bottom, and the flow has open boundaries on both sides. At first sight, it is similar to suspended microfluidics, with a 90° rotation. However, it is very different from suspended microfluidics when considering the concepts of microfluidic networks. Such networks are not compatible with suspended geometries. SCF conditions in rail geometries are detailed in the chapter. Different rails morphologies are investigated.

Chapter 7 presents the development of paper-based microfluidics. Paper-based systems were first proposed long ago by Yagoda in the year 1937 [94]. They have recently seen a considerable revival with the developments of paper-strips and µPADs (micro paper-based analytical-devices). Strips are narrow bands of cellulose fiber where the liquid wicks the fibers and progresses in one direction and where the reaction zones are regions placed perpendicularly to the flow (figure 5). µPADs are two-dimensional planar devices where reaction zones are placed at the extremity of branches [76]. It appears that the solutions provided by labs-on-paper are very promising and have a large scope of applications [95]. In this chapter the principles, designs, detection methods and fabrication processes of paper-based devices and labs-on-paper are presented.

Figure 5 A: Sketch of paper strips. B: Photograph of a µPAD. From [98], reprinted with permission ©2014 Springer. C: Close up of a thread showing the fiber bundle. From [78], reprinted with permission ©2010 ACS.

The final chapter of the book, chapter 8, is dedicated to thread-based microfluidics. It is a very new domain, which has recently seen new developments [79,80]. The concept of thread-based microfluidics is the use of fibers to guide and transport liquids. The particular physics of fiber wicking is developed in the chapter, and applications to smart bandages are presented.

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