Disposable sensors are low-cost and easy-to-use sensing devices intended for short-term or rapid single-point measurements. The growing demand for fast, accessible, and reliable information in a vastly connected world makes disposable sensors increasingly important. The areas of application for such devices are numerous, ranging from pharmaceutical, agricultural, environmental, forensic, and food sciences to wearables and clinical diagnostics, especially in resource-limited settings. The capabilities of disposable sensors can extend beyond measuring traditional physical quantities (for example, temperature or pressure); they can provide critical chemical and biological information (chemo- and biosensors) that can be digitized and made available to users and centralized/decentralized facilities for data storage, remotely. These features could pave the way for new classes of low-cost systems for health, food, and environmental monitoring that can democratize sensing across the globe. Here, a brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis. Finally, views on how the field of disposable sensing devices will continue its evolution are discussed, including the future trends, challenges, and opportunities.

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Disposable Sensors in Diagnostics, Food, and Environmental Monitoring.

Multiplexed Point-of-Care Testing – xPOCT

Almost all pneumatic and hydraulic actuators useful for mesoscale functions rely on hard valves for control. This article describes a soft, elastomeric valve that contains a bistable membrane, which acts as a mechanical “switch” to control air flow. A structural instability—often called “snap-through”—enables rapid transition between two stable states of the membrane. The snap-upward pressure, Δ P 1 (kilopascals), of the membrane differs from the snap-downward pressure, Δ P 2 (kilopascals). The values Δ P 1 and Δ P 2 can be designed by changing the geometry and the material of the membrane. The valve does not require power to remain in either “open” or “closed” states (although switching does require energy), can be designed to be bistable, and can remain in either state without further applied pressure. When integrated in a feedback pneumatic circuit, the valve functions as a pneumatic oscillator (between the pressures Δ P 1 and Δ P 2 ), generating periodic motion using air from a single source of constant pressure. The valve, as a component of pneumatic circuits, enables (i) a gripper to grasp a ball autonomously and (ii) autonomous earthworm-like locomotion using an air source of constant pressure. These valves are fabricated using straightforward molding and offer a way of integrating simple control and logic functions directly into soft actuators and robots.

A soft, bistable valve for autonomous control of soft actuators

The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or “three-dimensional (3D) printing” technologies – predominantly stereolithography – as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) – a layer-by-layer, multi-material inkjetting process – for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community.

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3D printed microfluidic circuitry via multijet-based additive manufacturing

It has been more than 20 years since the first micro total analysis systems (μTAS) papers were published. Initial reports of these devices, which are also commonly referred to as Labs-on-a-Chip (LOC), LabChips, microchips or microfluidic devices, generally focused on separations and the development of a variety of functional elements for sample manipulation and handling. One of the greatest potentials of μTAS, however, has always been in the integration of multiple functional elements to produce truly sample-in/answer-out systems. In the last decade, the march toward developing such integrated devices has accelerated significantly. Many μTAS reported now are quite sophisticated with multiple sample handling and processing steps that are highly integrated and often automated. While most of these devices are not yet strictly sample-in/answer-out several come quite close. There are, however, some significant hurdles still facing the development of true sample-in/answer-out systems especially in the areas of sample preparation, chip-to-real-world interfacing and detection. Additionally, further progress is needed in the miniaturization or elimination of external fluidic control elements.

μTAS have found a major niche in the areas of biological and biomedical analyses, especially cellular and nucleic acid analysis. This focus on biological applications reflects the capabilities of these devices to precisely and accurately handle picoliter volumes of materials and to integrate cell transport, culturing or trapping with reagent delivery, and on-chip detection. Significant progress has been made in the development of a variety of cellular analysis systems; this field, however, is still rapidly growing and many papers focused on the expansion of such capabilities continue to be seen. Areas of focus remain the development of substrate materials and culturing conditions that do not unnaturally perturb or stress cells and that allow for extended culturing so that changes in cell physiology over time can be monitored. In addition, a significant amount of work has been directed to developing cell co-cultures on μTAS to mimic tissues, organs, and organ systems. μTAS can create unique, controlled environments to study cell-cell interactions that can not be replicated in any other way. For cellular assays substantial increases in throughput are also a focus. While significant development toward completely integrated cell assays has occurred and even some clinical demonstrations of such assays have been reported, the availability of commercial, fully integrated devices, however, has lagged.

In addition to biological assays, the creative expansion of the basic μTAS toolkit with centrifugal platforms, digital microfluidics, and paper-based devices has substantially expanded its potential application base. Interest in these devices is generally more clinical in nature and again focused on generating sample-in/answer-out analyses. Significant work, however, is still needed for most of these platforms in terms of substrate materials, fluid control, sample handling, integration and throughput. Finally, the development of label-free detection technologies remains of interest.

This review focuses on recent advances in μTAS technology in the areas of integrated biological assays and diagnostics with an analytical focus. We have also tried to highlight some material, fabrication, coating, separation, and detection advances with more general applicability. We have not included, for the most part, papers on synthesis, biosensors, theory, simulations or reviews. The papers included in this review were published between September 2012 and September 2013. The material was compiled using several strategies including extensive searches using Scifinder, Web of Science, PubMed, and Google Scholar. The contents of high impact journals were also scanned, including Analytical Chemistry, Lab-on-a-Chip, Nature, PNS, Appl. Phys., Letters, and Langmuir. Almost 2000 papers relating in some way to microfluidics were examined. We have done our best to try to identify some of the most interesting and promising papers and to report on them in this review. Without a doubt we have missed a few excellent papers and had to eliminate others based on space constraints and readability. For those papers that we have failed to include, we apologize in advance and welcome comments regarding any oversight that we have made.

Micro total analysis systems: fundamental advances and biological applications.

The scaling of integrated circuits to smaller dimensions is critical for achieving increased system complexity and speed. Digital logic circuits composed of pneumatic microfluidic components have to this point been limited to a circuit density of 2–4 gates cm−2, constraining the complexity of the digital systems that can be achieved. We explored the use of precision machining techniques to reduce the size of pneumatic valves and resistors, and to achieve more accurate and efficient placement of ports and vias. In this way, we attained an order of magnitude increase in circuit density, reaching as high as 36 gates cm−2. A 12-bit binary counter circuit composed of 96 gates was realized in an area of 360 mm2. The reduction in size also brought an order of magnitude increase in speed. The frequency of a 13-stage ring oscillator increased from 2.6 Hz to 22.1 Hz, and the maximum clock frequency of a binary counter increased from 1/3 Hz to 6 Hz.

Scaling of pneumatic digital logic circuits

This report presents a liquid-handling chip capable of executing metering, mixing, incubation, and wash procedures largely under the control of on-board pneumatic circuitry. The only required inputs are four static selection lines to choose between the four machine states, and one additional line for power. State selection is simple: constant application of vacuum to an input causes the device to execute one of its four liquid handling operations. Programmed control of 31 valves, including fast coordinated cycling for peristaltic pumping, is accomplished by pneumatic digital logic circuits built out of microfluidic valves and channels rather than electronics, eliminating the need for the off-chip control machinery that is typically required for integrated microfluidics.

Semi-autonomous liquid handling via on-chip pneumatic digital logic

Serial dilution is a fundamental procedure that is common to a large number of laboratory protocols. Automation of serial dilution is thus a valuable component for lab-on-a-chip systems. While a handful of different microfluidic strategies for serial dilution have been reported, approaches based on continuous flow mixing inherently consume larger amounts of sample volume and chip real estate. We employ valve-driven circulatory mixing to address these issues and also introduce a novel device structure to store each stage of the dilution process. The dilution strategy is based on sequentially mixing the rungs of a ladder structure. We demonstrate a 7-stage series of 1 : 1 dilutions with R2 equal to 0.995 in an active device area of 1 cm2.

Microfluidic serial dilution ladder

Previously described selective plane illumination microscopy techniques typically offset ease of use and sample handling for maximum imaging performance or vice versa. Also, to reduce cost and complexity while maximizing flexibility, it is highly desirable to implement light sheet microscopy such that it can be added to a standard research microscope instead of setting up a dedicated system. We devised a new approach termed sideSPIM that provides uncompromised imaging performance and easy sample handling while, at the same time, offering new applications of plane illumination towards fluidics and high throughput 3D imaging of multiple specimen. Based on an inverted epifluorescence microscope, all of the previous functionality is maintained and modifications to the existing system are kept to a minimum. At the same time, our implementation is able to take full advantage of the speed of the employed sCMOS camera and piezo stage to record data at rates of up to 5 stacks/s. Additionally, sample handling is compatible with established methods and switching magnification to change the field of view from single cells to whole organisms does not require labor intensive adjustments of the system.

sideSPIM - selective plane illumination based on a conventional inverted microscope.

Pseudomonas aeruginosa is an opportunistic, multidrug-resistant, human pathogen that forms biofilms in environments with fluid flow, such as the lungs of cystic fibrosis patients, industrial pipelines, and medical devices. P. aeruginosa twitches upstream on surfaces by the cyclic extension and retraction of its mechanoresponsive type IV pili motility appendages. The prevention of upstream motility, host invasion, and infectious biofilm formation in fluid flow systems remains an unmet challenge. Here, we describe the design and application of scalable nanopillared surface structures fabricated using nanoimprint lithography that reduce upstream motility and colonization by P. aeruginosa. We used flow channels to induce shear stress typically found in catheter tubes and microscopy analysis to investigate the impact of nanopillared surfaces with different packing fractions on upstream motility trajectory, displacement, velocity, and surface attachment. We found that densely packed, subcellular nanopillared surfaces, with pillar periodicities ranging from 200 to 600 nm and widths ranging from 70 to 215 nm, inhibit the mechanoresponsive upstream motility and surface attachment. This bacteria-nanostructured surface interface effect allows us to tailor surfaces with specific nanopillared geometries for disrupting cell motility and attachment in fluid flow systems.

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Siavash Ahrar

Papers

Scaling of pneumatic digital logic circuits

Semi-autonomous liquid handling via on-chip pneumatic digital logic

Microfluidic serial dilution ladder

sideSPIM - selective plane illumination based on a conventional inverted microscope.

Nanopillared Surfaces Disrupt Pseudomonas aeruginosa Mechanoresponsive Upstream Motility.