Surface microfluidics fabricated by photopatternable superhydrophobic nanocomposite

Surface microfluidics can be of potential use in a variety of emerging applications, including biological and chemical analysis, cellular detection and manipulation, high-throughput pharmaceutical screening, and etc. In comparison with the conventional closed-channel microfluidic system, surface microfluidics shows the distinct advantages of simple construction, direct surface access, no cavitation or interphase obstruction, clear optical path, easy fluidic packaging, and device reusability. In this article, we first present surface microfluidic networks microfabricated by a single-step lithographic process using a novel superhydrophobic photosensitive nanocomposite formula. The photopatternable superhydrophobic nanocomposite (PSN) incorporates PTFE nanoparticles into a SU-8 matrix, in which superhydrophobicity (contact angle of above 160°) is primarily contributed by the extremely low chemical energy and nano-topology of PTFE nanoparticles, while the SU-8 polymer matrix offers photopatternability (lithographic resolution of 10 μm) and substrate adhesion. Moreover, an additive intermediate layer with hydrophilic sidewall considerably reduces flow resistance while improving the substrate adhesion, as a crucial improvement from the previous surface flow configuration. Furthermore, self-propelled microfluidic networks driven by surface tension-induced pressure gradient have been fabricated and characterized to demonstrate the applicability of the novel nanocomposite fabrication approach.     

Optofluidic dye lasers

Optofluidic dye lasers are microfabricated liquid dye lasers enabled by the microfluidics technology. The integration of dye lasers with microfluidics not only facilitates the implementation of complete “lab-on-a-chip” systems, but also allows the dynamical control of the laser properties which is not achievable with solid-state optical components. We review the recent demonstrations of on-chip liquid dye lasers and some of the pre-microfluidics era microscopic dye lasers which are also amenable to microfluidic implementation. Potential applications and future directions are discussed.     

Microfluidic devices containing thin rock sections for oil recovery studies

While there has been a shift towards renewable energy sources, oil remains an important source of not only energy but also raw materials. Oil recovery is currently an inefficient process with as much as 50% of the original oil remaining in a field. Improvement of oil recovery techniques requires a model system that is both chemically and physically representative to achieve accurate results. Current large laboratory scale systems use large cores drilled from target rock and large, high-pressure systems to recreate oil recovery systems. The cores and associated equipment required to accurately model oil recovery are expensive and time consuming to obtain and operate. As a result, there has been a continual quest to develop alternative solutions that are faster, less complicated, and less expensive while still providing accurate representation of reservoirs. An alternative to large-scale models are optically transparent two or three-dimensional microfluidic devices. Several examples of microfluidic devices used to study oil recovery processes have been published. Unfortunately, most microfluidic devices require complicated fabrication techniques, inaccurately replicate the reservoir rock surface chemistry and geometry, and are made from materials not representative of surfaces found in oil reservoirs. Herein, the Flow On Rock Device is described as an easy to fabricate microfluidic device that acts as a bridge between fully synthetic microfluidics and large laboratory models due to incorporation of reservoir rock samples directly into the microfluidic device. Results of flooding studies are presented on shale and sandstone models as an example of the potential for this system in studying oil recovery.     

Sample preconcentration in microfluidic devices

Microfluidic systems have attracted considerable attention and have experienced rapid growth in the past two decades due to advantages associated with miniaturization, integration, and automation. Poor detection sensitivities mainly attributed to the small dimensions of these lab-on-a-chip (LOC) devices; however, sometimes can greatly hinder their practical applications in detecting low-abundance analytes, particularly those in bio-samples. Although off-chip sample pretreatment strategies can be used to address this problem prior to analysis, they may introduce contaminants or lead to an undesirable loss of some original sample volume. Moreover, they are often time-consuming and labor-intensive. Toward the goals of automation, improvement in analytical efficiency, and reductions in sample loss and contamination, many on-chip sample preconcentration techniques based on different working principles for improving the detection sensitivity have been developed and implemented in microchips. The aim of this article is to review recent works in microchip-based sample preconcentration techniques and give detailed discussions about these techniques. We start with a brief introduction regarding the importance of preconcentration techniques in microfluidics and the classification of these techniques based on their concentration mechanisms, followed by in-depth discussions of about these techniques. Finally, personal perspectives on microfluidic-based sample preconcentration will be provided. These advancements in microfluidic sample preconcentration techniques may provide promising strategies for improving the detection sensitivities of LOC devices in many practical applications.     

Microfluidic platforms for discovery and detection of molecular biomarkers

Microfluidics has emerged as a promising platform for discovery and detection of molecular biomarkers recently. With this approach, the discovery of these biomarkers could be more efficient in time and consumes less samples and reagents. Furthermore, the entire discovery process could be automated since all the functional microfluidic devices such as micropumps and microvalves could be integrated on a single chip. Similarly, the detection of the discovered molecular biomarkers is also promising. Detection of nucleic acid biomarkers, protein biomarkers, and metabolite biomarkers has been demonstrated on microfluidic platforms recently. When compared with their large-scale counterparts, the miniature system can perform the detection of these biomarkers within less analysis time while a multiplexed detection scheme could be easily achieved. Furthermore, the entire detection process could be automated on the single chip as well. This review paper is therefore to review the recent development of microfluidic devices and systems for the discovery and detection of the molecular biomarker. Techniques for biomarker discovery, verification, and detection that have been adapted into microfluidics were first reviewed, and their advantages were highlighted. The new approach of biomarker screening based on in vitro-generated affinity reagents such as nucleic acid aptamers and peptide affinity reagents was then reviewed. Finally, in the biomarker detection section, this review placed a special emphasis on commercialized microfluidic-based diagnostics for molecular biomarkers.     

Microfluidic applications of functionalized magnetic particles for environmental analysis: focus on waterborne pathogen detection

The continuous surveillance of drinking water is extremely important to provide early warning of contamination and to ensure continuous supplies of healthy drinking water. Isolation and detection of a particular type of pathogen present at low concentration in a large volume of water, concentrating the analyte in a small detection volume, and removing detection inhibiting factors from the concentrated sample, present the three most important challenges for water quality monitoring laboratories. Combining advanced biological detection methods (e.g., nucleic acid-based or immunology-based protocols) with microfluidics and immunomagnetic separation techniques that exploit functionalized magnetic particles has tremendous potential for realization of an integrated system for pathogen detection, in particular, of waterborne pathogens. Taking advantage of the unique properties of magnetic particles, faster, more sensitive, and more economical diagnostic assays can be developed that can assist in the battle against microbial pathogenesis. In this review, we highlight current technologies and methods used for realization of magnetic particle-based microfluidic integrated waterborne pathogen isolation and detection systems, which have the potential to comply in future with regulatory water quality monitoring requirements.     

Fabrication of multilayer systems combining microfluidic andmicrooptical elements for fluorescence detection

This paper presents the fabrication of a microchemical chip for the detection of fluorescence species in microfluidics. The microfluidic network is wet-etched in a Borofloat 33 (Pyrex) glass wafer and sealed by means of a second wafer. Unlike other similar chemical systems, the detection system is realized with the help of microfabrication techniques and directly deposited on both sides of the microchemical chip. The detection system is composed of the combination of refractive microlens arrays and chromium aperture arrays. The microfluidic channels are 60 μm wide and 25 μm deep. The utilization of elliptical microlens arrays to reduce aberration effects and the integration of an intermediate (between the two bonded wafers) aluminum aperture array are also presented. The elliptical microlenses have a major axis of 400 μm and a minor axis of 350 μm. The circular microlens diameters range from 280 to 300 μm. The apertures deposited on the outer chip surfaces are etched in a 3000-Å-thick chromium layer, whereas the intermediate aperture layer is etched in a 1000-Å-thick aluminum layer. The overall thickness of this microchemical system is less than 1.6 mm. The wet-etching process and new bonding procedures are discussed. Moreover, we present the successful detection of a 10-nM Cy5 solution with a signal-to-noise ratio (SNR) of 21 dB by means of this system     

Microfluidic-based biosensors toward point-of-care detection of nucleic acids and proteins

This article reviews state-of-the-art microfluidic biosensors of nucleic acids and proteins for point-of-care (POC) diagnostics. Microfluidics is capable of analyzing small sample volumes (10⁻⁹–10⁻¹⁸ l) and minimizing costly reagent consumption as well as automating sample preparation and reducing processing time. The merger of microfluidics and advanced biosensor technologies offers new promises for POC diagnostics, including high-throughput analysis, portability and disposability. However, this merger also imposes technological challenges on biosensors, such as high sensitivity and selectivity requirements with sample volumes orders of magnitude smaller than those of conventional practices, false response errors due to non-specific adsorption, and integrability with other necessary modules. There have been many prior review articles on microfluidic-based biosensors, and this review focuses on the recent progress in last 5 years. Herein, we review general technologies of DNA and protein biosensors. Then, recent advances on the coupling of the biosensors to microfluidics are highlighted. Finally, we discuss the key challenges and potential solutions for transforming microfluidic biosensors into POC diagnostic applications.     

Thin-film electrode based droplet detection for microfluidic systems

We report on a droplet-producing microfluidic system with electrical impedance-based detection. The microfluidic devices are made of polydimethylsiloxane (PDMS) and glass with thin film electrodes connected to an impedance-monitoring circuit. Immiscible fluids containing the hydrophobic and hydrophilic phases are injected with syringe pumps and spontaneously break into water-in-oil droplet trains. When a droplet passes between a pair of electrodes in a medium having different electrical conductivity, the resulting impedance change signals the presence of the particle for closed-loop feedback during processing. The circuit produces a digital pulse for input into a computer control system. The droplet detector allows estimation of a droplet's arrival time at the microfluidic chip outlet for dispensing applications. Droplet detection is required in applications that count, sort, and direct microfluidic droplets. Because of their low cost and simplicity, microelectrode-based droplet detection techniques should find applications in digital microfluidics and in three-dimensional printing technology for rapid prototyping and biotechnology.     

Droplet transport by electrowetting: lets get rough!

Since the pioneering works of Wenzel and Cassie Baxter in the 1930s, and now with the trivialization of the micro- and nanotechnology facilities, superhydrophobic surfaces have been announced as potentially amazing components for applications such as fluidic, optical, electronic, or thermal devices. In this paper, we show that using superhydrophobic surfaces in digital microfluidic devices could solve some usual limitations or enhance their performances. Thus, we investigate a specific monophasic (air environment) microfluidic device based on electrowetting integrating either a hydrophobic or a superhydrophobic surface as a counter-electrode. The droplet transport using a superhydrophobic surface compared with a classical hydrophobic system led to some original results. Characterization of the dynamic contact angle and the droplet shape allows us to get new insight of the fluid dynamics. Among the remarkable properties reported, a 30 % lower applied voltage, a 30 % higher average speed with a maximum instantaneous speed of 460 mm/s have been measured. Furthermore, we have noticed a huge droplet deformation leading to an increase by a factor 5 of the Weber number (from 1.4 to 7.0) on SH compared to hydrophobic surfaces. Finally, we discuss some of the repercussions of this behaviour especially for microfluidic device.     

Microfluidic systems for diagnostic applications: a review

Because of intensive developments in recent years, the microfluidic system has become a powerful tool for biological analysis. Entire analytic protocols including sample pretreatment, sample/reagent manipulation, separation, reaction, and detection can be integrated into a single chip platform. A lot of demonstrations on the diagnostic applications related to genes, proteins, and cells have been reported because of their advantages associated with miniaturization, automation, sensitivity, and specificity. The aim of this article is to review recent developments in microfluidic systems for diagnostic applications. Based on the categories of various fluid-manipulating mechanisms and biological detection approaches, in-depth discussion of the microfluidic-based diagnostic systems is provided. Moreover, a brief discussion on materials and manufacturing techniques will be included. The current excellent integration of microfluidic systems and diagnostic applications suggests a solid foundation for the development of practical point-of-care devices.     

采用DVD光学头的微流细胞计的细胞分析

一、引言流动血细胞计是当细胞通过盛满液流的设备时,单个生物细胞的物理或者生化特征被检测出来的一个系统。这些系统往往基于光学或者阻抗的测量方法,其中光学流动细胞计是最重要的商业化产品。物理参数如细胞密度或者单个细胞尺寸可以通过基于直流/低频交流阻抗测试法或者高频信号的库尔特计数器(Coulter Counter)获取。使用阻抗频谱参数仪,膜电容和细胞浆电导率等可以在细胞流经时获取。     

Particle/cell separation on microfluidic platforms based on centrifugation effect: a review

Particle/cell separation in heterogeneous mixtures including biological samples is a standard sample preparation step for various biomedical assays. A wide range of microfluidic-based methods have been proposed for particle/cell sorting and isolation. Two promising microfluidic platforms for this task are microfluidic chips and centrifugal microfluidic disks. In this review, we focus on particle/cell isolation methods that are based on liquid centrifugation phenomena. Under this category, we reviewed particle/cell sorting methods which have been performed on centrifugal microfluidic platforms, and inertial microfluidic platforms that contain spiral channels and multi-orifice channels. All of these platforms implement a form of centrifuge-based particle/cell separation: either physical platform centrifugation in the case of centrifugal microfluidic platforms or liquid centrifugation due to Dean drag force in the case of inertial microfluidics. Centrifugal microfluidic platforms are suitable for cases where the preparation step of a raw sample is required to be integrated on the same platform. However, the limited available space on the platform is the main disadvantage, especially when high sample volume is required. On the other hand, inertial microfluidics (spiral and multi-orifice) showed various advantages such as simple design and fabrication, the ability to process large sample volume, high throughput, high recovery rate, and the ability for multiplexing for improved performance. However, the utilization of syringe pump can reduce the portability options of the platform. In conclusion, the requirement of each application should be carefully considered prior to platform selection.     

Optofluidic integration for microanalysis

This review describes recent research in the application of optical techniques to microfluidic systems for chemical and biochemical analysis. The “lab-on-a-chip” presents great benefits in terms of reagent and sample consumption, speed, precision, and automation of analysis, and thus cost and ease of use, resulting in rapidly escalating adoption of microfluidic approaches. The use of light for detection of particles and chemical species within these systems is widespread because of the sensitivity and specificity which can be achieved, and optical trapping, manipulation and sorting of particles show significant benefits in terms of discrimination and reconfigurability. Nonetheless, the full integration of optical functions within microfluidic chips is in its infancy, and this review aims to highlight approaches, which may contribute to further miniaturisation and integration.     

Bench scale glass-to-glass bonding for microfluidic prototyping

Microfluidics, an increasingly ubiquitous technology platform, has been extensively utilized in assorted research areas. Commonly, microfluidic devices are fabricated using cheap and convenient elastomers such as poly(dimethylsiloxane) (PDMS). However, despite the popularity of these materials, their disadvantages such like deformation under moderate pressure, chemical incompatibility, and surface heterogeneity have been widely recognized as impediments to expanding the utility of microfluidics. Glass-based microfluidic devices, on the other hand, exhibit desirable properties including rigidity, chemically inertness, and surface chemistry homogeneity. That the universal adoption of glass-based microfluidics has not yet been achieved is largely attributable to the difficulties in device fabrication and bonding, which usually require large capital investment. Therefore, in this work, we have developed a bench-scale glass-to-glass bonding protocol that allows the automated bonding of glass microfluidic devices within 6 h via a commercially available furnace. The quality of the bonds was inspected comprehensively in terms of bonding strength, channel deformation and reliability. Additionally, femtosecond pulsed laser micromachining was employed to rapidly engrave channels on a glass substrate with arbitrary-triangular in this case-cross-section. Bonded glass microfluidic devices with machined channels have been used to verify calculated capillary entry pressures. This combination of fast laser micromachining that produces arbitrary cross-sectioned microstructures and convenient bench-scale glass bonding protocol will facilitate a broad range of micro-scale applications.

     

Soft lithography fabrication of index-matched microfluidic devices for reducing artifacts in fluorescence and quantitative phase imaging

Microfluidic devices are widely used for biomedical applications based on microscopy or other optical detection methods. However, the materials commonly used for microfabrication typically have a high refractive index relative to water, which can create artifacts at device edges and limit applicability to applications requiring high-precision imaging or morphological feature detection. Here we present a soft lithography method to fabricate microfluidic devices out of MY133-V2000, a UV-curable, fluorinated polymer with low refractive index that is close to that of water (n = 1.33). The primary challenge in the use of this material (and fluorinated materials in general) is the low adhesion of the fluorinated material; we present several alternative fabrication methods we have tested to improve inter-layer adhesion. The close match between the refractive index of this material and aqueous solutions commonly used in biomedical applications enables fluorescence imaging at microchannel or other microfabricated edges without distortion. The close match in refractive index also enables quantitative phase microscopy imaging across the full width of microchannels without error-inducing artifacts for measurement of cell biomass. Overall, our results demonstrate the utility of low-refractive index microfluidics for biological applications requiring high-precision optical imaging.     

An integrated microfluidic system for live bacteria detection from human joint fluid samples by using ethidium monoazide and loop-mediated isothermal amplification

Periprosthetic joint infection (PJI) is one of the severe complications of prosthetic joint replacement. Delayed PJI diagnosis may anchor bacteria in periprosthetic tissues, and removal of the prosthesis might be inevitable. The diagnosis of PJI depends on the identification of microorganisms by standard microbiological cultures or more advanced molecular diagnostic methods for detection of bacterial genes. However, these methods are relatively time-consuming, labor-intensive and not human error-free. Moreover, it is challenging to distinguish live from dead bacteria by using DNA-based molecular diagnostics since bacterial DNA will be remained in the tissue even after the death of the bacteria. In this work, an integrated microfluidic system has been developed to perform the entire molecular diagnostic process for the PJI diagnosis in a single chip. We combined the loop-mediated isothermal amplification (LAMP) with ethidium monoazide (EMA) in an integrated microfluidic system to identify live bacteria with reasonable sensitivity and high specificity. All the diagnostic processes including bacteria isolation, cell lysis, DNA amplification and optical detection can be automatically performed on the integrated microfluidic system by using a compact custom-made control system. The integrated system can accommodate four primers complementary to six regions of the target genes and improve the detection limit by using LAMP. The limit of detection in this multiple EMA-LAMP assay could be as low as 5 fg/reaction (~1 CFU/reaction) when choosing an optimized primer set as we demonstrated in mecA gene detection. Thus, the developed system for PJI diagnosis has great potential to become a point-of-care device.     

Sample Processing with Hydrophobic Microfluidics

Hydrophobic microfluidics is a method for controlling fluid flow in microfluidic systems using short restrictions in channel diameter that act as passive valves. Systems designed using hydrophobic microfluidics have the advantage of easily interfacing with external hardware and integrating with external analysis equipment. This allows it to take advantage of both the micro and macro realms, whichever is most suited for the application, as well as allowing for an inexpensive integration of microfluidics into a company's sample analysis protocols. This method of fluid control is excellent for highly parallel sample analysis, such as DNA processing.     

Microfluidics enables small-scale tissue-based drug metabolism studies with scarce human tissue

Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither are ideal predictors of drug behavior in humans. Improving in vitro systems for preclinical studies both from a technological and biological model standpoint thus remains a major challenge. This article describes how microfluidics can be exploited to come closer to this goal in combination with precision-cut liver slices (PCLS) as an improved organomimetic system. Recently, we developed a novel microfluidic-based system incorporating a microchamber for slice perifusion to perform drug metabolism studies with mammalian PCLS under continuous flow. In the present study, the viability and metabolism of human PCLS were assessed by the measurement of the leakage of liver-specific enzymes and metabolism of four different substrates: lidocaine, 7-hydroxycoumarin, 7-ethoxycoumarin, and testosterone. All experiments were verified with well plates, an excellent benchmark for these experiments. Clearly, however, human tissue is not readily available, and it is worth considering how to perform a maximum number of informative experiments with small amounts of material. In one approach, the microfluidic system was coupled to an HPLC system to allow on-line monitoring and immediate detection of unstable metabolites, something that is generally not possible with conventional well-plate systems. This novel microfluidic system also enables the in vitro measurement of interorgan interactions by connecting microchambers containing different organ slices in series for sequential perfusion. This versatile experimental system has the potential to yield more information about the metabolic profiles of new drug candidates in human and animal tissues in an early stage of development compared with well plates alone.     

Optofluidics technology based on colloids and their assemblies

Optofluidic technology is believed to provide a breakthrough for the currently underlying problems in microfluidics and photonics/optics by complementary integration of fluidics and photonics. The key aspect of the optofluidics technology is based on the use of fluidics for tuning the optical properties and addressing various functional materials inside of microfluidic channels which have build-in photonic structures. Through the optofluidic integrations, fluidics enhances the controllability and tunability of optical systems. In particular, colloidal dispersion gives novel properties such as photonic band-gaps and enhanced Raman spectrum that conventional optofluidic devices cannot exhibit. In this paper, the state of the art of the colloidal dispersions is reviewed especially for optofluidic applications. From isolated singlet colloidal particles to colloidal clusters, their self-organized assemblies lead to optical manipulation of the photonic/optical properties and responses. Finally, we will discuss the prospects of the integrated optofluidics technology based on colloidal systems.