Passive Microfluidic System Research Articles

Self-Sustaining Water Microdroplet Resonators Using 3D-Printed Microfluidics.

Microdroplet resonators provide an excellent tool for optical studies of water, but water microdroplets are difficult to maintain outside a carefully controlled environment. We present a method for maintaining a water microdroplet resonator on a 3D-printed hydrophobic surface in an ambient environment. The droplet is maintained through a passive microfluidic system that supplies water to the droplet through a vertical channel at a rate equivalent to its evaporation. In this manner, we are able to create and passively maintain water microdroplet resonators with quality factors as high as 3×108.

Rheotaxis of sperm: Hydrodynamics behavior of human sperm in a passive microfluidic system

Rheotaxis of sperm: Hydrodynamics behavior of human sperm in a passive microfluidic system

Inkjet Electrodes for Developing Wearable Sensors for the Detection of Peptides and Neurotransmitters in Sweat Using Flexible Materials

In recent years, there has been an increased interest in the research and development of 2D materials for use and application in different fields, such as new technologies, medicine, health care, flexible biosensors, and wearable devices. Our goal is based on developing a flexible wearable biosensor for the skin to detect in real-time neurotransmitters and neuropeptides in human sweat. The development of flexible biosensors for detecting molecules in sweat has been of great interest. However, the problem is that most research has focused on a limited number of molecules such as lactate, chloride and potassium ions, glucose, and pH, and there is a great need to develop flexible biosensors that can monitor real-time molecules that are not yet studied in sweat. One of our molecules of great interest is neuropeptide Y (NPY). NPY has an essential role in the energy balance and is related to different diseases and conditions such as diabetes, obesity, depression, anxiety, and sleep problems and has recently been found to be associated with cardiovascular problems.Our biosensor consists of flexible, low-cost materials that do not require much manufacturing time. The proposed flexible sensor system consists of paper-based microfluidics that serve as our system's passive flow method and silver inkjet electrodes printed on the PET surface. Microfluidic systems can be characterized as active or passive, depending on the force applied to the sample or flow. We can perform minimal flow or particles in a minimum amount of liquid or a sample flow with paper-based microfluidics systems. Among the passive microfluidic systems, paper-based microfluidics, also known as micro-pads, are among the most promising methods because they are easy to manufacture, inexpensive, and have low sample volume. One of the most popular techniques to develop electrochemical wearable biosensors is the fabrication of microelectrode arrays through inkjet printing. To fabricate our electrode arrays, we first created the design in AutoCAD and then printed it using silver conductive ink and a commercial inkjet printer. Since sweat is a complex fluid, it is necessary to modify the working electrode's surface to give the electrode's selectivity towards the molecule to be analyzed or detected. To achieve the detection of NPY, we first add carboxyl groups to the surface of the working electrode, which will serve as an anchor for the specific aptamer for NPY. We use different buffer solutions like artificial cerebrospinal fluid, phosphate buffer solutions, and artificial sweat to perform electrochemical characterization on our silver inkjet electrodes through cyclic voltammetry and electrochemical impedance spectroscopy (EIS). We decreased the oxidation of the surface of our electrodes by changing the buffer and modifying the surface for greater selectivity towards NPY. Using 2D materials, we managed to manufacture and electrochemically characterize our flexible biosensor system prototypes to detect neuropeptides and neurotransmitters in sweat, applying the use of paper-based microfluidics and silver inkjet electrodes printed on PET and paper surfaces.

High precision, high throughput generation of droplets containing single cells.

The Poisson limit is a major problem for the isolation of single cells in different single-cell technologies and applications. In droplet-based single-cell assays, a scheme that is increasingly popular, the intrinsic randomness during single-cell encapsulation in droplets requires most of the created droplets to be empty, which has a profound impact on the efficiency and throughput of such techniques, and on the predictability of the combinatory droplet assays. Here we present a simple passive microfluidic system overcoming this limitation with unprecedented efficacy, allowing the generation of single-cell droplets for a wide range of operating conditions, with extremely high throughput (more than 22 000 single-cell loaded droplets per minute) and with an extremely low fault ratio (doublets or empty droplets), applicable to any cells and deformable particles. This versatile technique will shift the paradigm of single-cell encapsulation and will impact single-cell sequencing, rare cell isolation, multicellular/bead studies in immunology or cancer biology, etc.

Direct Infusion ICP-qMS of Lined-up Single-Cell Using an Oil-Free Passive Microfluidic System.

When coupled online with mass spectrometry (MS), widely applied water-in-oil droplet-based microfluidics for single cell analysis met problems. For example, the oil phase rumpled the stability, efficiency, and accuracy of MS, the conventional interface between MS and the microfluidic chip suffered the low sample introduction efficiency, and the transportation rates sometimes unmatched the readout dwell times for transient signal acquisition. Considering cells are already "droplets" with hydrophilic surface and elastic hydrophobic membrane, we developed an oil-free passive microfluidic system (OFPMS) that consists of alternating straight-curved-straight microchannels and a direct infusion (dI) micronebulizer for inductively coupled plasma quadrupole-based mass spectrometry (ICP-qMS) of lined-up single-cell. OFPMS guarantees exact single cell isolation one by one just using a thermo-decomposable NH4HCO3 buffer, eliminating the use of any oil and incompatible polymer carriers. It is more flexible and facile to adapt to the dwell time of ICP-qMS owing to the adjustable throughput of 400 to 25000 cells/min and the controllable interval time of at least 20 ms between the lined-up adjacent single cells. Quantitative single-cell transportation and high detection efficiency of more than 70% was realized using OFPMS-dI-ICP-qMS exemplified here. Thus, cell-to-cell heterogeneity can be simply uncovered via the determination of metals in the individual cells.

Improving the longevity of passive microfluidic systems through plasma polymer films with a vertical chemical gradient

Capillary driven microfluidic devices rely on hydrophilic surfaces to facilitate and control the fluid flow inside microchannels. This can be accomplished through the deposition of a highly functional plasma polymer film (PPF) on the surface of the device. Highly functional plasma polymer films exhibit ageing effects characterized by oxidation, degradation, swelling, dissolution, and restructuring at the surface to minimize the surface energy. The application of plasma polymer films in microfluidics is, therefore, limited by this instability. To overcome this limitation, plasma polymer films in the form of a vertical chemical gradient structure were deposited on the surface of microfluidic devices designed to perform immunodiagnostics for use during space missions. The vertical chemical gradient PPFs were composed of a highly cross-linked base layer with gradually less cross-linked and more functional surface layers. The highly cross-linked base layer of the gradient structure effectively hindered restructuring at the surface of the film, resulting in a more stable surface composition and surface wettability than that of the more traditional non-gradient structure. In addition, the microfluidics prepared using a gradient structure showed more stable chip runtimes. The stability of the gradient plasma polymer films will allow for their implementation in microfluidics, as well as a diverse range of biomedical applications such as drug delivery and the generation of antibacterial coatings.

A Passive Microfluidic Device for Chemotaxis Studies.

This work presents a disposable passive microfluidic system, allowing chemotaxis studies, through the generation of a concentration gradient. The device can handle liquid flows without an external supply of pressure or electric gradients, but simply using gravity force. It is able to ensure flow rates of 10 µL/h decreasing linearly with 2.5% in 24 h. The device is made of poly(methylmethacrylate) (PMMA), a biocompatible material, and it is fabricated by micro-milling and solvent assisted bonding. It is assembled into a mini incubator, designed properly for cell biology studies in passive microfluidic devices, which provides control of temperature and humidity levels, a contamination-free environment for cells with air and 5% of CO2. Furthermore, the mini incubator can be mounted on standard inverted optical microscopes. By using our microfluidic device integrated into the mini incubator, we are able to evaluate and follow in real-time the migration of any cell line to a chemotactic agent. The device is validated by showing cell migration at a rate of 0.36 µm/min, comparable with the rates present in scientific literature.

Passive and parallel microfluidic formation of droplet interface bilayers (DIBs) for measurement of leakage of small molecules through artificial phospholipid membranes

We present a passive microfluidic system for easy and rapid generation of Droplet Interface Bilayer pairs, each formed with two aqueous nanoliter droplets comprising controlled chemical composition. The system allows for rapid screening to quantify leakage of small molecules through artificial phospholipid bilayers. The droplets are generated, diluted and stored in-situ on the microfluidic chip. Our device comprises microfluidic Meter&Store (M&S) modules – hydrodynamic traps, which enable hard-wired operations on small – ca. 9 nL in volume – aqueous droplets including splitting, merging and derailing the droplets to side storage wells. Consequently, the droplets are locked and positioned next to each other and form bilayers at the point of contact between the nanoliter aqueous compartments. Additionally, a set of trap modules provides the possibility for in situ preparation of dilutions of a sample. We demonstrated the basic capacity of the trap-based system for formation of an array of 12 (controllably different) lipid bilayers in less than 5 min. Thanks to the small volumes of the droplets, the system is capable for monitoring the transport across the artificial membrane within a relatively short interval – opening the possibility to use dyes and alleviating the difficulty of parallel electrophysiological measurements. We use this functionality to prepare on-chip dilutions of small molecules and determine their permeation rates through the bilayer. Finally, we used the M&S system and calcium sensitive dyes to quantify the ion flux through the model α-hemolysin (αHL) nanopores.

A passive microfluidic system based on step emulsification allows the generation of libraries of nanoliter-sized droplets from microliter droplets of varying and known concentrations of a sample.

We present a novel geometry of microfluidic channels that allows us to passively generate monodisperse emulsions of hundreds of droplets smaller than 1 nL from collections of larger (ca. 0.4 μL) mother droplets. We introduce a new microfluidic module for the generation of droplets via passive break-up at a step. The module alleviates a common problem in step emulsification with efficient removal of the droplets from the vicinity of the step. In our solution, the droplets are pushed away from the step by a continuous liquid that bypasses the mother droplets via specially engineered bypasses that lead to the step around the main channel. We show that the bypasses tighten the distribution of volume of daughter droplets and eliminate subpopulations of daughter droplets. Clearing away the just produced droplets from the vicinity of the step provides for similar conditions of break-up for every subsequent droplet and, consequently, leads to superior monodispersity of the generated emulsions. Importantly, this function is realized autonomously (passively) in a protocol in which only a sequence of large mother droplets is forced through the module. Our system features the advantage of step emulsification systems in that the volumes of the generated droplets depend very weakly on the rate of flow through the module - an increase in the flow rate by 300% causes only a slight increase of the average diameter of generated droplets by less than 5%. We combined our geometry with a simple T-junction and a simple trap-based microdroplet dilutor to produce a collection of libraries of droplets of gradually changing and known concentrations of a sample. The microfluidic system can be operated with only two syringe pumps set at constant rates of flow during the experiment.

Advances in ion beam micromachining for complex 3D microfluidics

In this paper, the authors present microfluidic mixers containing complex curvilinear and several tens of microns deep three-dimensional (3D) geometries used to decrease mixing lengths in passive microfluidic systems. In order to create these 3D geometries, the authors use ion beam micromachining (IBμM) and address redeposition and exposure strategy effects that follow this type of fabrication. Results of this work clearly demonstrate that fabrication of 3D microfluidic mixers using IBμM is achievable for real practical applications. In order to scale up to the tens of microns width and depth, and hundreds of microns in length fabrication, high current is required. This raises unique challenges of redeposition handling. This was achieved by realizing that redeposited silicon can be removed with an extended buffered oxide etch. In addition, data management and writing strategies not encountered in electron beam lithography have to be considered when designing the solid to be milled. Both designs, straight 3D and serpentine 3D mixers, were significantly faster mixers than the standard focusing mixer with no 3D texturing. This demonstrates that adding programmed depth variations to existing microfluidic devices can open new opportunities in microfluidic research and IBμM.

Three-dimensional microfluidic mixers using ion beam lithography and micromachining

In this article, the authors present microfluidic mixers containing three-dimensional (3D) geometries used to decrease mixing lengths in passive microfluidic systems. In order to create these 3D geometries, the authors use ion beam lithography and micromachining and address charging, redeposition, and stitching error effects that follow this type of fabrication. Prior to mixer fabrication, simulations were run and results were compared between a common straight mixer and two other mixers designed by the authors. The simulation results have shown that 3D geometries can generate lateral velocities and lower mixing lengths down to approximately 70 μm.

Valves for autonomous capillary systems

Autonomous capillary systems (CSs) are microfluidic systems inside which liquids move owing to capillary forces. CSs can in principle bring the high-performances of microfluidic-based analytical devices to near patient and environmental testing applications. In this paper, we show how wettable capillary valves can enhance CSs with novel functionalities, such as delaying and stopping liquids in microchannels. The valves employ an abruptly changing geometry of the flow path to delay a moving liquid filling front in a wettable microchannel. We show how to combine delay valves with capillary pumps, prevent shortcuts of liquid along the corners of microfluidic channels, stop liquids filling microchannels from a few seconds to over 30 min, trigger valves using two liquid fronts merging, and time a liquid using parallel microfluidic paths converging to a trigger valve. All together, these concepts should add functionality to passive microfluidic systems without departing from their initial simplicity of use.

Interface motion of capillary-driven flow in rectangular microchannel.

In microchannel flow, gas-liquid interface behavior is important for developing a wide range of microfluidic applications, especially in passive microfluidic systems. This paper presents a discussion of interface motion driven by capillary action in a microchannel. We have extended the theory beyond the previous theory of capillary rise problem for a circular tube, to a rectangular microchannel. The same formula for the relation between nondimensional time and interface position is obtained as for a circular tube. We examined rectangular microchannels with several sizes (about 50 to 100 microm square) of glass capillaries and 85 x 68 microm and 75 x 45 microm polydimethylsiloxane (PDMS) microchannels fabricated by photolithography technique, respectively. We observed movement of the gas-liquid interface position and compared it to the dimensionless relation. We obtained the value of a dimensionless variable of driving force that is related to dynamic contact angles for glass-water, glass-ethanol, and PDMS-ethanol. Using this variable, interface motion can be predicted for any size of rectangular channels.

Disposable Smart Lab on a Chip for Point-of-Care Clinical Diagnostics

This paper presents the development of a disposable plastic biochip incorporating smart passive microfluidics with embedded on-chip power sources and integrated biosensor array for applications in clinical diagnostics and point-of-care testing. The fully integrated disposable biochip is capable of precise volume control with smart microfluidic manipulation without costly on-chip microfluidic components. The biochip has a unique power source using on-chip pressurized air reservoirs, for microfluidic manipulation, avoiding the need for complex microfluidic pumps. In addition, the disposable plastic biochip has successfully been tested for the measurements of partial oxygen concentration, glucose, and lactate level in human blood using an integrated biosensor array. This paper presents details of the smart passive microfluidic system, the on-chip power source, and the biosensor array together with a detailed discussion of the plastic micromachining techniques used for chip fabrication. A handheld analyzer capable of multiparameter detection of clinically relevant parameters has also been developed to detect the signals from the cartridge type disposable biochip. The handheld analyzer developed in this work is currently the smallest analyzer capable of multiparameter detection for point-of-care testing.