scispace - formally typeset
Search or ask a question

Showing papers in "Lab on a Chip in 2010"


Journal ArticleDOI
TL;DR: This critical review discusses the current understanding of the formation, transport, and merging of drops in microfluidics and focuses on the physical ingredients which determine the flow of Drops in microchannels.
Abstract: This critical review discusses the current understanding of the formation, transport, and merging of drops in microfluidics. We focus on the physical ingredients which determine the flow of drops in microchannels and recall classical results of fluid dynamics which help explain the observed behaviour. We begin by introducing the main physical ingredients that differentiate droplet microfluidics from single-phase microfluidics, namely the modifications to the flow and pressure fields that are introduced by the presence of interfacial tension. Then three practical aspects are studied in detail: (i) The formation of drops and the dominant interactions depending on the geometry in which they are formed. (ii) The transport of drops, namely the evaluation of drop velocity, the pressure-velocity relationships, and the flow field induced by the presence of the drop. (iii) The fusion of two drops, including different methods of bridging the liquid film between them which enables their merging.

900 citations


Journal ArticleDOI
TL;DR: The fabrication and the performance of microfluidic paper-based electrochemical sensing devices are described and it is demonstrated that the microPEDs are capable of quantifying the concentrations of various analytes in aqueous solutions.
Abstract: This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, µPEDs). The µPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the µPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world.

851 citations


Journal ArticleDOI
TL;DR: An in-depth review of the centrifugal microfluidic platform, while highlighting recent progress in the field and outlining the potential for future applications, is presented in this paper.
Abstract: The centrifugal microfluidic platform has been a focus of academic and industrial research efforts for almost 40 years. Primarily targeting biomedical applications, a range of assays have been adapted on the system; however, the platform has found limited commercial success as a research or clinical tool. Nonetheless, new developments in centrifugal microfluidic technologies have the potential to establish wide-spread utilization of the platform. This paper presents an in-depth review of the centrifugal microfluidic platform, while highlighting recent progress in the field and outlining the potential for future applications. An overview of centrifugal microfluidic technologies is presented, including descriptions of advantages of the platform as a microfluidic handling system and the principles behind centrifugal fluidic manipulation. The paper also discusses a history of significant centrifugal microfluidic platform developments with an explanation of the evolution of the platform as it pertains to academia and industry. Lastly, we review the few centrifugal microfluidic-based sample-to-answer analysis systems shown to date and examine the challenges to be tackled before the centrifugal platform can be more broadly accepted as a new diagnostic platform. In particular, fully integrated, easy to operate, inexpensive and accurate microfluidic tools in the area of in vitro nucleic acid diagnostics are discussed.

620 citations


Journal ArticleDOI
TL;DR: An easy and rapid microfluidic immunoaffinity method to isolate microvesicles from small volumes of both serum from blood samples and conditioned medium from cells in culture is presented.
Abstract: Microvesicles (exosomes) shed from both normal and cancerous cells may serve as means of intercellular communication. These microvesicles carry proteins, lipids and nucleic acids derived from the host cell. Their isolation and analysis from blood samples have the potential to provide information about state and progression of malignancy and should prove of great clinical importance as biomarkers for a variety of disease states. However, current protocols for isolation of microvesicles from blood require high-speed centrifugation and filtration, which are cumbersome and time consuming. In order to take full advantage of the potential of microvesicles as biomarkers for clinical applications, faster and simpler methods of isolation will be needed. In this paper, we present an easy and rapid microfluidic immunoaffinity method to isolate microvesicles from small volumes of both serum from blood samples and conditioned medium from cells in culture. RNA of high quality can be extracted from these microvesicles providing a source of information about the genetic status of tumors to serve as biomarkers for diagnosis and prognosis of cancer.

504 citations


Journal ArticleDOI
TL;DR: This compact and light-weight holographic microscope installed on a cellphone does not utilize any lenses, lasers or other bulky optical components and it may offer a cost-effective tool for telemedicine applications to address various global health challenges.
Abstract: We demonstrate lensfree digital microscopy on a cellphone. This compact and light-weight holographic microscope installed on a cellphone does not utilize any lenses, lasers or other bulky optical components and it may offer a cost-effective tool for telemedicine applications to address various global health challenges. Weighing ∼38 grams (<1.4 ounces), this lensfree imaging platform can be mechanically attached to the camera unit of a cellphone where the samples are loaded from the side, and are vertically illuminated by a simple light-emitting diode (LED). This incoherent LED light is then scattered from each micro-object to coherently interfere with the background light, creating the lensfree hologram of each object on the detector array of the cellphone. These holographic signatures captured by the cellphone permit reconstruction of microscopic images of the objects through rapid digital processing. We report the performance of this lensfree cellphone microscope by imaging various sized micro-particles, as well as red blood cells, white blood cells, platelets and a waterborne parasite (Giardia lamblia).

476 citations


Journal ArticleDOI
TL;DR: The combination of simple Electrochemical Micro-Paper-based Analytical Devices (EµPADs) with commercially available glucometers allows rapid, quantitative electrochemical analysis of a number of compounds relevant to human health in blood or urine.
Abstract: The combination of simple Electrochemical Micro-Paper-based Analytical Devices (EµPADs) with commercially available glucometers allows rapid, quantitative electrochemical analysis of a number of compounds relevant to human health (e.g., glucose, cholesterol, lactate, and alcohol) in blood or urine.

471 citations


Journal ArticleDOI
TL;DR: This lensless incoherent holographic microscope has orders-of-magnitude improved light collection efficiency and is very robust to mechanical misalignments it may offer a cost-effective tool especially for telemedicine applications involving various global health problems in resource limited settings.
Abstract: Despite the rapid progress in optical imaging, most of the advanced microscopy modalities still require complex and costly set-ups that unfortunately limit their use beyond well equipped laboratories. In the meantime, microscopy in resource-limited settings has requirements significantly different from those encountered in advanced laboratories, and such imaging devices should be cost-effective, compact, light-weight and appropriately accurate and simple to be usable by minimally trained personnel. Furthermore, these portable microscopes should ideally be digitally integrated as part of a telemedicine network that connects various mobile health-care providers to a central laboratory or hospital. Toward this end, here we demonstrate a lensless on-chip microscope weighing ∼46 grams with dimensions smaller than 4.2 cm × 4.2 cm × 5.8 cm that achieves sub-cellular resolution over a large field of view of ∼24 mm2. This compact and light-weight microscope is based on digital in-line holography and does not need any lenses, bulky optical/mechanical components or coherent sources such as lasers. Instead, it utilizes a simple light-emitting-diode (LED) and a compact opto-electronic sensor-array to record lensless holograms of the objects, which then permits rapid digital reconstruction of regular transmission or differential interference contrast (DIC) images of the objects. Because this lensless incoherent holographic microscope has orders-of-magnitude improved light collection efficiency and is very robust to mechanical misalignments it may offer a cost-effective tool especially for telemedicine applications involving various global health problems in resource limited settings.

463 citations


Journal ArticleDOI
TL;DR: The results suggest that the microfluidic device presented here is useful for resembling an in vivo renal tubule system and has potential applications in drug screening and advanced tissue engineering.
Abstract: We have developed a simple multi-layer microfluidic device by integrating a polydimethyl siloxane (PDMS) microfluidic channel and a porous membrane substrate to culture and analyze the renal tubular cells. As a model cell type, primary rat inner medullary collecting duct (IMCD) cells were cultured inside the channel. To generate in vivo-like tubular environments for the cells, a fluidic shear stress of 1 dyn/cm2 was applied for 5 hours, allowing for optimal fluidic conditions for the cultured cells, as verified by enhanced cell polarization, cytoskeletal reorganization, and molecular transport by hormonal stimulations. These results suggest that the microfluidic device presented here is useful for resembling an in vivo renal tubule system and has potential applications in drug screening and advanced tissue engineering.

443 citations


Journal ArticleDOI
TL;DR: Combination of a mathematical modeling approach (PK-PD modeling) and an in vitro experimental approach (microCCA) provides a novel platform with improved predictability for testing drug toxicity and can help researchers gain a better insight into the drug's mechanism of action.
Abstract: Drug discovery is often impeded by the poor predictability of in vitro assays for drug toxicity. One primary reason for this observation is the inability to reproduce the pharmacokinetics (PK) of drugs in vitro. Mathematical models to predict the pharmacokinetics-pharmacodynamics (PK-PD) of drugs are available, but have several limitations, preventing broader application. A microscale cell culture analog (microCCA) is a microfluidic device based on a PK-PD model, where multiple cell culture chambers are connected with fluidic channels to mimic multi-organ interactions and test drug toxicity in a pharmacokinetic-based manner. One critical issue with microfluidics, including the microCCA, is that specialized techniques are required for assembly and operation, limiting its usability to non-experts. Here, we describe a novel design, with enhanced usability while allowing hydrogel-cell cultures of multiple types. Gravity-induced flow enables pumpless operation and prevents bubble formation. Three cell lines representing the liver, tumor and marrow were cultured in the three-chamber microCCA to test the toxicity of an anticancer drug, 5-fluorouracil. The result was analyzed with a PK-PD model of the device, and compared with the result in static conditions. Each cell type exhibited differential responses to 5-FU, and the responses in the microfluidic environment were different from those in static environment. Combination of a mathematical modeling approach (PK-PD modeling) and an in vitro experimental approach (microCCA) provides a novel platform with improved predictability for testing drug toxicity and can help researchers gain a better insight into the drug's mechanism of action.

425 citations


Journal ArticleDOI
TL;DR: Cell-encapsulated hydrogels with complex three-dimensional structures were fabricated from photopolymerizable poly(ethylene glycol) diacrylate (PEGDA), and the feasibility of depositing multiple cell types and material compositions into distinct layers was established.
Abstract: Cell-encapsulated hydrogels with complex three-dimensional (3D) structures were fabricated from photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) using modified 'top-down' and 'bottoms-up' versions of a commercially available stereolithography apparatus (SLA). Swelling and mechanical properties were measured for PEGDA hydrogels with molecular weights (M(w)) ranging from 700 to 10 000 Daltons (Da). Long-term viability of encapsulated NIH/3T3 cells was quantitatively evaluated using an MTS assay and shown to improve over 14 days by increasing the M(w) of the hydrogels. Addition of adhesive RGDS peptide sequences resulted in increased cell viability, proliferation, and spreading compared to pristine PEG hydrogels of the same M(w). Spatial 3D layer-by-layer cell patterning was successfully demonstrated, and the feasibility of depositing multiple cell types and material compositions into distinct layers was established.

422 citations


Journal ArticleDOI
TL;DR: A bioreactor is developed that fosters maintenance of 3D tissue cultures under constant perfusion and multiple bioreactors are integrated into an array in a multiwell plate format to capture the complexity of in vivo tissue and organ behaviors.
Abstract: In vitro models that capture the complexity of in vivo tissue and organ behaviors in a scalable and easy-to-use format are desirable for drug discovery. To address this, we have developed a bioreactor that fosters maintenance of 3D tissue cultures under constant perfusion and we have integrated multiple bioreactors into an array in a multiwell plate format. All bioreactors are fluidically isolated from each other. Each bioreactor in the array contains a scaffold that supports formation of hundreds of 3D microscale tissue units. The tissue units are perfused with cell culture medium circulated within the bioreactor by integrated pneumatic diaphragm micropumps. Electronic controls for the pumps are kept outside the incubator and connected to the perfused multiwell by pneumatic lines. The docking design and open-well bioreactor layout make handling perfused multiwell plates similar to using standard multiwell tissue culture plates. A model of oxygen consumption and transport in the circulating culture medium was used to predict appropriate operating parameters for primary liver cultures. Oxygen concentrations at key locations in the system were then measured as a function of flow rate and time after initiation of culture to determine oxygen consumption rates. After seven days of culture, tissue formed from cells seeded in the perfused multiwell reactor remained functionally viable as assessed by immunostaining for hepatocyte and liver sinusoidal endothelial cell (LSEC) phenotypic markers.

Journal ArticleDOI
TL;DR: This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices.
Abstract: In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.

Journal ArticleDOI
TL;DR: Geometrically enhanced differential immunocapture and an antibody for prostate-specific membrane antigen (PSMA) are used for high-efficiency and high-purity capture of prostate circulating tumor cells from peripheral whole blood samples of castrate-resistant prostate cancer patients.
Abstract: Geometrically enhanced differential immunocapture (GEDI) and an antibody for prostate-specific membrane antigen (PSMA) are used for high-efficiency and high-purity capture of prostate circulating tumor cells from peripheral whole blood samples of castrate-resistant prostate cancer patients.

Journal ArticleDOI
TL;DR: Methods of controlling fluid transport using the geometry of the network and dissolvable barriers are demonstrated and the implications for higher sensitivity detection using this type of 2D paper network are discussed.
Abstract: Recent reports have demonstrated the multi-analyte detection capability of paper networks with multiple outlets per inlet. In this report, we focus on the capabilities of 2D paper networks with multiple inlets per outlet and demonstrate the controlled transport of reagents within paper devices. Specifically, we demonstrate methods of controlling fluid transport using the geometry of the network and dissolvable barriers. Finally, we discuss the implications for higher sensitivity detection using this type of 2D paper network.

Journal ArticleDOI
TL;DR: Three-dimensional microfluidic paper-based analytical devices (3-D microPADs) that can be programmed (postfabrication) by the user to generate multiple patterns of flow through them are described.
Abstract: This paper describes three-dimensional microfluidic paper-based analytical devices (3-D µPADs) that can be programmed (postfabrication) by the user to generate multiple patterns of flow through them. These devices are programmed by pressing single-use ‘on’ buttons, using a stylus or a ballpoint pen. Pressing a button closes a small space (gap) between two vertically aligned microfluidic channels, and allows fluids to wick from one channel to the other. These devices are simple to fabricate, and are made entirely out of paper and double-sided adhesive tape. Programmable devices expand the capabilities of µPADs and provide a simple method for controlling the movement of fluids in paper-based channels. They are the conceptual equivalent of field-programmable gate arrays (FPGAs) widely used in electronics.

Journal ArticleDOI
TL;DR: This approach has the potential for future applications in cost-effective hematology or rare-cell analysis platforms with extreme throughput capabilities when integrated with suitable large field-of view imaging or interrogation methods.
Abstract: Rapid and accurate differentiation of cell types within a heterogeneous solution is a challenging but important task for various applications in biological research and medicine. Flow cytometry is the gold standard in cell analysis and is regularly used for blood analysis (i.e., complete blood counts). Flow cytometry, however, lacks sufficient throughput to analyze rare cells in blood or other dilute solutions in a reasonable time period because it is an inherently serial process. In this study, we exploit inertial effects for label- and sheath-free parallel flow cytometry with extreme throughput. We demonstrate a microfluidic device that consists of 256 high-aspect (W = 16 µm, H = 37 µm) parallel channels yielding a sample rate up to 1 million cells s−1, only limited by the field-of-view of our high-speed optical interrogation method. The particles or cells flowing through the channels are focused to one uniform z-position (SD = ±1.81 µm) with uniform downstream velocity (Uave = 0.208 ± 0.004 m s−1) to reduce the probability of overlap and out-of-focus blur and provide similar cell signature images for accurate detection and analysis. To demonstrate a proof-of-concept application of our system operating at these throughputs, we conducted automated RBC and leukocyte counts on diluted whole blood and achieved high counting sensitivity and specificity (86–97%) compared to visual inspection of raw images. As no additional external forces are required to create ordered streams of cells, this approach has the potential for future applications in cost-effective hematology or rare-cell analysis platforms with extreme throughput capabilities when integrated with suitable large field-of view imaging or interrogation methods.

Journal ArticleDOI
TL;DR: For the first time, a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA) is demonstrated and excels existing PCR based lab- on- a-chip platforms in terms of energy efficiency and time-to-result.
Abstract: For the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37 °C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into ≤30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow-molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time-to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems.

Journal ArticleDOI
TL;DR: A novel microfluidic cell sorter which operates in continuous flow at high sorting rates and has successfully directed HaCaT cells (human keratinocytes), fibroblasts from mice and MV3 melanoma cells.
Abstract: We describe a novel microfluidic cell sorter which operates in continuous flow at high sorting rates. The device is based on a surface acoustic wave cell-sorting scheme and combines many advantages of fluorescence activated cell sorting (FACS) and fluorescence activated droplet sorting (FADS) in microfluidic channels. It is fully integrated on a PDMS device, and allows fast electronic control of cell diversion. We direct cells by acoustic streaming excited by a surface acoustic wave which deflects the fluid independently of the contrast in material properties of deflected objects and the continuous phase; thus the device underlying principle works without additional enhancement of the sorting by prior labelling of the cells with responsive markers such as magnetic or polarizable beads. Single cells are sorted directly from bulk media at rates as fast as several kHz without prior encapsulation into liquid droplet compartments as in traditional FACS. We have successfully directed HaCaT cells (human keratinocytes), fibroblasts from mice and MV3 melanoma cells. The low shear forces of this sorting method ensure that cells survive after sorting.

Journal ArticleDOI
TL;DR: This work revisits well-known microfluidic devices for hydrodynamic focusing, sized-based extraction of molecules from complex mixtures, micromixing, and dilution, and demonstrates that paper-based devices can replace their expensive conventional micro fluidic counterparts.
Abstract: Conventional microfluidic devices typically require highly precise pumps or pneumatic control systems, which add considerable cost and the requirement for power. These restrictions have limited the adoption of microfluidic technologies for point-of-care applications. Paper networks provide an extremely low-cost and pumpless alternative to conventional microfluidic devices by generating fluid transport through capillarity. We revisit well-known microfluidic devices for hydrodynamic focusing, sized-based extraction of molecules from complex mixtures, micromixing, and dilution, and demonstrate that paper-based devices can replace their expensive conventional microfluidic counterparts.

Journal ArticleDOI
TL;DR: It is demonstrated using microfluidics that stiffer malaria-infected RBCs (iRBCs) behave similar to leukocytes and undergo margination towards the sidewalls, which provides better understanding of the hemodynamic effects of iR BCs in microcirculation and its contribution to pathophysiological outcome relating to cytoadherence to endothelium.
Abstract: In blood vessels with luminal diameter less than 300μm, red blood cells (RBCs) which are smaller in size and more deformable than leukocytes, migrate to the axial centre of the vessel due to flow velocity gradient within the vessels. This phenomenon displaces the leukocytes to the vessel wall and is aptly termed as margination. Here, we demonstrate using microfluidics that stiffer malaria-infected RBCs (iRBCs) behave similar to leukocytes and undergo margination towards the sidewalls. This provides better understanding of the hemodynamic effects of iRBCs in microcirculation and its contribution to pathophysiological outcome relating to cytoadherence to endothelium. In this work, cell margination is mimicked for the separation of iRBCs from whole blood based on their reduced deformability. The malaria infected sample was tested in a simple long straight channel microfluidic device fabricated in polydimethylsiloxane. In this microchannel, cell margination was directed along the channel width with the iRBCs aligning near each sidewall and then subsequently removed using a 3-outlet system, thus achieving separation. Tests were conducted using ring stage and late trophozoite/schizont stage iRBCs. Device performance was quantified by analyzing the distribution of these iRBCs across the microchannel width at the outlet and also conducting flow cytometry analysis. Results indicate recovery of ∼75% for early stage iRBCs and >90% for late stage iRBCs at the side outlets. The simple and passive system operation makes this technique ideal for on-site iRBCs enrichment in resource-limited settings, and can be applied to other blood cell diseases, e.g. sickle cell anemia and leukemia, characterized by changes in cell stiffness.

Journal ArticleDOI
Feng Shen1, Wenbin Du1, Jason E. Kreutz1, Alice Fok1, Rustem F. Ismagilov1 
TL;DR: The SlipChip provides a simple strategy to count nucleic acids by using PCR that may find applications in research applications such as single cell analysis, prenatal diagnostics, and point-of-care diagnostics and would become valuable for diagnostics after integration with isothermal nucleic acid amplification technologies and visual readout.
Abstract: This paper describes a SlipChip to perform digital PCR in a very simple and inexpensive format. The fluidic path for introducing the sample combined with the PCR mixture was formed using elongated wells in the two plates of the SlipChip designed to overlap during sample loading. This fluidic path was broken up by simple slipping of the two plates that removed the overlap among wells and brought each well in contact with a reservoir preloaded with oil to generate 1280 reaction compartments (2.6 nL each) simultaneously. After thermal cycling, end-point fluorescence intensity was used to detect the presence of nucleic acid. Digital PCR on the SlipChip was tested quantitatively by using Staphylococcus aureus genomic DNA. As the concentration of the template DNA in the reaction mixture was diluted, the fraction of positive wells decreased as expected from the statistical analysis. No cross-contamination was observed during the experiments. At the extremes of the dynamic range of digital PCR the standard confidence interval determined using a normal approximation of the binomial distribution is not satisfactory. Therefore, statistical analysis based on the score method was used to establish these confidence intervals. The SlipChip provides a simple strategy to count nucleic acids by using PCR. It may find applications in research applications such as single cell analysis, prenatal diagnostics, and point-of-care diagnostics. SlipChip would become valuable for diagnostics, including applications in resource-limited areas after integration with isothermal nucleic acid amplification technologies and visual readout.

Journal ArticleDOI
TL;DR: The critical review of the state of Lab-on-a-Foil applications with a special focus on nucleic acid analysis, immunoassays, cell-based assays and home care testing concludes that the Lab- on-a -Foil approach is very versatile and significantly expands the toolbox for the development of Lab -on- a-Chip solutions.
Abstract: This critical review is motivated by an increasing interest of the microfluidics community in developing complete Lab-on-a-Chip solutions based on thin and flexible films (Lab-on-a-Foil). Those implementations benefit from a broad range of fabrication methods that are partly adopted from well-established macroscale processes or are completely new and promising. In addition, thin and flexible foils enable various features like low thermal resistance for efficient thermocycling or integration of easily deformable chambers paving the way for new means of on-chip reagent storage or fluid transport. From an economical perspective, Lab-on-a-Foil systems are characterised by low material consumption and often low-cost materials which are attractive for cost-effective high-volume fabrication of self-contained disposable chips. The first part of this review focuses on available materials, fabrication processes and approaches for integration of microfluidic functions including liquid control and transport as well as storage and release of reagents. In the second part, an analysis of the state of Lab-on-a-Foil applications is provided with a special focus on nucleic acid analysis, immunoassays, cell-based assays and home care testing. We conclude that the Lab-on-a-Foil approach is very versatile and significantly expands the toolbox for the development of Lab-on-a-Chip solutions.

Journal ArticleDOI
TL;DR: Two microfluidic devices capable of selectively isolating live human leukemia cells from dead cells utilizing their electrical signatures are presented, achieving greater than 95% removal efficiency and 100% selectivity between live and dead cells.
Abstract: Contactless dielectrophoresis (cDEP) is a recently developed method of cell manipulation in which the electrodes are physically isolated from the sample. Here we present two microfluidic devices capable of selectively isolating live human leukemia cells from dead cells utilizing their electrical signatures. The effect of different voltages and frequencies on the gradient of the electric field and device performance was investigated numerically and validated experimentally. With these prototype devices we were able to achieve greater than 95% removal efficiency at 0.2–0.5 mm s−1 with 100% selectivity between live and dead cells. In conjunction with enrichment, cDEP could be integrated with other technologies to yield fully automated lab-on-a-chip systems capable of sensing, sorting, and identifying rare cells.

Journal ArticleDOI
TL;DR: An overview of recent developments in artificial bacterial flagella (ABFs) is presented and discusses challenges and opportunities in pursuing applications, including the manipulation of small objects within liquid.
Abstract: This article presents an overview of recent developments in artificial bacterial flagella (ABFs) and discusses challenges and opportunities in pursuing applications. These helical swimmers possess several advantageous characteristics, such as high swimming velocity and precise motion control indicating their potential for diverse applications. One application is the manipulation of small objects within liquid, which is the focus of this review. Preliminary results have shown that ABFs are capable of performing microobject manipulation either directly by mechanical contact or indirectly by generating a localized fluid flow. The latter approach can be used for batch manipulation without direct contact, also implying possibilities for flow control in lab-on-a-chip systems. Miniaturized helical swimmers are also promising for biomedical applications, such as targeted drug delivery and implantation or removal of tissues and other objects.

Journal ArticleDOI
TL;DR: The design, fabrication, and characterisation of an array of optical slot-waveguide ring resonator sensors, integrated with microfluidic sample handling in a compact cartridge, for multiplexed real-time label-free biosensing is presented.
Abstract: We present the design, fabrication, and characterisation of an array of optical slot-waveguide ring resonator sensors, integrated with microfluidic sample handling in a compact cartridge, for multiplexed real-time label-free biosensing. Multiplexing not only enables high throughput, but also provides reference channels for drift compensation and control experiments. Our use of alignment tolerant surface gratings to couple light into the optical chip enables quick replacement of cartridges in the read-out instrument. Furthermore, our novel use of a dual surface-energy adhesive film to bond a hard plastic shell directly to the PDMS microfluidic network allows for fast and leak-tight assembly of compact cartridges with tightly spaced fluidic interconnects. The high sensitivity of the slot-waveguide resonators, combined with on-chip referencing and physical modelling, yields a volume refractive index detection limit of 5 × 10−6 refractive index units (RIUs) and a surface mass density detection limit of 0.9 pg mm−2, to our knowledge the best reported values for integrated planar ring resonators.

Journal ArticleDOI
TL;DR: The different biological single-cell assays that have been performed to date are described and how each individual application requires a particular device design are described, e.g. well-, trap-, pattern-, and droplet-based structures.
Abstract: Numerous microdevices developed for single-cell analyses have been presented in the last decades. Practical usefulness in biological and clinical settings has become an important focus during the development and implementation of new structures and assays. Single-cell analysis has been applied in intracellular research, gene- and protein content and expression, PCR, cell culture and division, clone formation, differentiation, morphology, lysis, separation, sorting, cytotoxicity and fluorescence screens, antibody secretion, etc. as discussed here along with brief descriptions of the technical devices used for the studies, e.g. well-, trap-, pattern-, and droplet-based structures. This review aims to serve as an overview of available techniques for single-cell analysis by describing the different biological single-cell assays that have been performed to date and how each individual application requires a particular device design.

Journal ArticleDOI
TL;DR: The first lab-on-a-chip platform for complete mammalian cell culture powered by digital microfluidics (DMF), a technique in which nanolitre-sized droplets are manipulated on an open surface of an array of electrodes, is introduced.
Abstract: We introduce the first lab-on-a-chip platform for complete mammalian cell culture. The new method is powered by digital microfluidics (DMF), a technique in which nanolitre-sized droplets are manipulated on an open surface of an array of electrodes. This is the first application of DMF to adherent cell culture and analysis, and more importantly, represents the first microfluidic platform capable of implementing all of the steps required for mammalian cell culture—cell seeding, growth, detachment, and re-seeding on a fresh surface. Three key innovations were required to implement complete cell culture on a microfluidic device: (1) a technique for growing cells on patterned islands (or “adhesion pads”) positioned on an array of DMF actuation electrodes; (2) a method for rapidly and efficiently exchanging media and other reagents on cells grown on adhesion pads; and (3) a system capable of detachment and collection of cells from an (old) origin site and delivery to a (new) destination site for subculture. The new technique was applied to cells from several different lines which were seeded and repeatedly subcultured for weeks at a time in 150 nL droplets. Cells handled in this manner exhibited growth characteristics and morphology comparable to those cultured in standard tissue culture vessels. To illustrate an application for this system, a microfluidic method was developed to implement transient transfection—we propose that the combination of this technique with multigenerational culture allows for “on-demand” generation of transiently transfected cells. Broadly, we anticipate that the automated cell microculture technique presented here will be useful in myriad applications that would benefit from automated mammalian cell culture.

Journal ArticleDOI
TL;DR: This paper performs plastic-PDMS bonding at room temperature, mediated by the formation of a chemically robust amine-epoxy bond at the interfaces, and investigates the potential of surface amine and epoxy functionalities as durable chemical adhesives by observing their storage-time-dependent bonding performances.
Abstract: Plastic materials do not generally form irreversible bonds with poly(dimethylsiloxane) (PDMS) regardless of oxygen plasma treatment and a subsequent thermal process. In this paper, we perform plastic-PDMS bonding at room temperature, mediated by the formation of a chemically robust amine–epoxy bond at the interfaces. Various plastic materials, such as poly(methylmethacrylate) (PMMA), polycarbonate (PC), polyimide (PI), and poly(ethylene terephthalate) (PET) were adopted as choices for plastic materials. Irrespective of the plastic materials used, the surfaces were successfully modified with amine and epoxy functionalities, confirmed by the surface characterizations such as water contact angle measurements and X-ray photoelectron spectroscopy (XPS), and chemically robust and irreversible bonding was successfully achieved within 1 h at room temperature. The bonding strengths of PDMS with PMMA and PC sheets were measured to be 180 and 178 kPa, respectively, and their assemblies containing microchannel structures endured up to 74 and 84 psi (510 and 579 kPa) of introduced compressed air, respectively, without destroying the microdevices, representing a robust and highly stable interfacial bonding. In addition to microchannel-molded PDMS bonded with flat plastic substrates, microchannel-embossed plastics were also bonded with a flat PDMS sheet, and both types of bonded assemblies displayed sufficiently robust bonding, tolerating an intense influx of liquid whose per-minute injection volume was nearly 1000 to 2000 times higher than the total internal volume of the microchannel used. In addition to observing the bonding performance, we also investigated the potential of surface amine and epoxy functionalities as durable chemical adhesives by observing their storage-time-dependent bonding performances.

Journal ArticleDOI
TL;DR: A new method is reported on how to measure the local pressure amplitude and the Q factor of ultrasound resonances in microfluidic chips designed for acoustophoresis of particle suspensions.
Abstract: A new method is reported on how to measure the local pressure amplitude and the Q factor of ultrasound resonances in microfluidic chips designed for acoustophoresis of particle suspensions. The method relies on tracking individual polystyrene tracer microbeads in straight water-filled silicon/glass microchannels. The system is actuated by a PZT piezo transducer attached beneath the chip and driven by an applied ac voltage near its eigenfrequency of 2 MHz. For a given frequency a number of particle tracks are recorded by a CCD camera and fitted to a theoretical expression for the acoustophoretic motion of the microbeads. From the curve fits we obtain the acoustic energy density, and hence the pressure amplitude as well as the acoustophoretic force. By plotting the obtained energy densities as a function of applied frequency, we obtain Lorentzian line shapes, from which the resonance frequency and the Q factor for each resonance peak are derived. Typical measurements yield acoustic energy densities of the order of 10 J/m3, pressure amplitudes of 0.2 MPa, and Q factors around 500. The observed half wavelength of the transverse acoustic pressure wave is equal within 2% to the measured width w = 377 μm of the channel.

Journal ArticleDOI
TL;DR: This rapid prototyping method can consistently achieve microchannels as thin as 200 microm in width and can be used to fabricate three-dimensional microfluidic devices using only double-sided pressure sensitive adhesive (PSA) tape and laser printer transparency film.
Abstract: Low-cost and straight forward rapid prototyping of flexible microfluidic devices using a desktop digital craft cutter is presented. This rapid prototyping method can consistently achieve microchannels as thin as 200 µm in width and can be used to fabricate three-dimensional (3D) microfluidic devices using only double-sided pressure sensitive adhesive (PSA) tape and laser printer transparency film. Various functional microfluidic devices are demonstrated with this rapid prototyping method. The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment.