Electrochemical Sensing of Urinary Chloride Ion Concentration for Near Real-Time Monitoring.

Urinary chloride concentration is a valuable health metric that can aid in the early detection of serious conditions, such as acid base disorders, acute heart failure, and incidences of acute renal failure in the intensive care unit. Physiologically, urinary chloride levels frequently change and are difficult to measure, involving time-consuming and inconvenient lab testing. Thus, near real-time simple sensors are needed to quickly provide actionable data to inform diagnostic and treatment decisions that affect health outcomes.

Dual-wavelength volumetric stereolithography of multilevel microfluidic devices.

Microfluidic devices are typically fabricated in an expensive, multistep process (e.g., photolithography, etching, and bonding).

A Variable Height Microfluidic Device for Multiplexed Immunoassay Analysis of Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is a leading cause of global morbidity and mortality, partially due to the lack of sensitive diagnostic methods and efficacious therapies. Panels of protein biomarkers have been proposed as a way of diagnosing and monitoring TBI. To measure multiple TBI biomarkers simultaneously, we present a variable height microfluidic device consisting of a single channel that varies in height between the inlet and outlet and can passively multiplex bead-based immunoassays by trapping assay beads at the point where their diameter matches the channel height.

The Current State of Traumatic Brain Injury Biomarker Measurement Methods.

Traumatic brain injury (TBI) is associated with high rates of morbidity and mortality partially due to the limited tools available for diagnosis and classification. Measuring panels of protein biomarkers released into the bloodstream after injury has been proposed to diagnose TBI, inform treatment decisions, and monitor the progression of the injury. Being able to measure these protein biomarkers at the point-of-care would enable assessment of TBIs from the point-of-injury to the patient's hospital bedside.

Co-cultivation of microbial sub-communities in microfluidic droplets facilitates high-resolution genomic dissection of microbial 'dark matter'.

While the 'unculturable' majority of the bacterial world is accessible with culture-independent tools, the inability to study these bacteria using culture-dependent approaches has severely limited our understanding of their ecological roles and interactions. To circumvent cultivation barriers, we utilize microfluidic droplets as localized, nanoliter-size bioreactors to co-cultivate subsets of microbial communities. This co-localization can support ecological interactions between a reduced number of encapsulated cells.

Variable-height channels for microparticle characterization and display.

Characterizing and isolating microparticles of different sizes is often desirable and essential for biological analysis. In this work, we present a new and straightforward technique to fabricate variable-height glass microchannels for size-based passive trapping of microparticles. The fabrication technique uses controlled non-uniform exposure to an etchant solution to create channels of arbitrary height that vary in a predetermined way from the inlet to the outlet.

A droplet-based microfluidic viscometer for the measurement of blood coagulation.

A continuous microfluidic viscometer is used to measure blood coagulation. The viscometer operates by flowing oil and blood into a cross section where droplets are generated. At a set pressure, the length of the droplets is inversely proportional to the viscosity of the blood sample being delivered.

Accuracy Evaluation of a Tetrabromophenolphthalein Ethyl Ester Colorimetric Assay for Urinary Albumin.

Background: The tetrabromophenolphthalein ethyl ester (TBPE) assay has been used to quantify urinary albumin in point-of-care devices. We assessed the accuracy of this TBPE assay for urinary albumin through comparison with an established immunoturbidimetric method (ADVIA 1800 Chemistry System, Siemens).

Methods: We developed a TBPE assay protocol to quantify albumin in the range associated with microalbuminuria (0-200 mg/L).

Volumetric Photopolymerization Confinement through Dual-Wavelength Photoinitiation and Photoinhibition.

Conventional photolithographic rapid prototyping approaches typically achieve reaction confinement in depth through patterned irradiation of a photopolymerizable resin at a wavelength where the resin strongly absorbs, such that only a very thin layer of material is solidified. Consequently, three-dimensional objects are fabricated by progressive, two-dimensional addition of material, curtailing fabrication rates and necessitating the incorporation of support structures to ensure the integrity of overhanging features. Here, we examine butyl nitrite as a UV-active photoinhibitor of blue light-induced photopolymerizations and explore its utilization to confine in depth the region polymerized in a volume of resin.

Rapid, continuous additive manufacturing by volumetric polymerization inhibition patterning.

Contemporary, layer-wise additive manufacturing approaches afford sluggish object fabrication rates and often yield parts with ridged surfaces; in contrast, continuous stereolithographic printing overcomes the layer-wise operation of conventional devices, greatly increasing achievable print speeds and generating objects with smooth surfaces. We demonstrate a novel method for rapid and continuous stereolithographic additive manufacturing by using two-color irradiation of (meth)acrylate resin formulations containing complementary photoinitiator and photoinhibitor species. In this approach, photopatterned polymerization inhibition volumes generated by irradiation at one wavelength spatially confine the region photopolymerized by a second concurrent irradiation wavelength.

Micro-Particle Operations Using Asymmetric Traps.

Micro-particle operations in many lab-on-a-chip devices require active-type techniques that are accompanied by complex fabrication and operation. The present study describes an alternative method using a passive microfluidic scheme that allows for simpler operation and, therefore, potentially less expensive devices. We present three practical micro-particle operations using our previously developed passive mechanical trap, the asymmetric trap, in a non-acoustic oscillatory flow field.

One-Way Particle Transport Using Oscillatory Flow in Asymmetric Traps.

One challenge of integrating of passive, microparticles manipulation techniques into multifunctional microfluidic devices is coupling the continuous-flow format of most systems with the often batch-type operation of particle separation systems. Here, a passive fluidic technique-one-way particle transport-that can conduct microparticle operations in a closed fluidic circuit is presented. Exploiting pass/capture interactions between microparticles and asymmetric traps, this technique accomplishes a net displacement of particles in an oscillatory flow field.

A Drinking Water Sensor for Lead and Other Heavy Metals.

Leakage of lead and other heavy metals into drinking water is a significant health risk and one that is not easily detected. We have developed simple sensors containing only platinum electrodes for the detection of heavy metal contamination in drinking water. The two-electrode sensor can identify the existence of a variety of heavy metals in drinking water, and the four-electrode sensor can distinguish lead from other heavy metals in solution.

Multifunctional Water Sensors for pH, ORP, and Conductivity Using Only Microfabricated Platinum Electrodes.

Monitoring of the pH, oxidation-reduction-potential (ORP), and conductivity of aqueous samples is typically performed using multiple sensors. To minimize the size and cost of these sensors for practical applications, we have investigated the use of a single sensor constructed with only bare platinum electrodes deposited on a glass substrate. The sensor can measure pH from 4 to 10 while simultaneously measuring ORP from 150 to 800 mV.

Bead mediated separation of microparticles in droplets.

Exchange of components such as particles and cells in droplets is important and highly desired in droplet microfluidic assays, and many current technologies use electrical or magnetic fields to accomplish this process. Bead-based microfluidic techniques offer an alternative approach that uses the bead's solid surface to immobilize targets like particles or biological material. In this paper, we demonstrate a bead-based technique for exchanging droplet content by separating fluorescent microparticles in a microfluidic device.

Viscosity Measurements Using Microfluidic Droplet Length.

Viscosity measurements have a wide range of applications from industrial chemical production to medical diagnosis. In this work, we have developed a simple droplet-based, water-in-oil continuous viscometer capable of measuring viscosity changes in 10 s or less and consuming a total sample volume of less than 1 μL/h. The viscometer employs a flow-focusing geometry and generates droplets under constant pressure.

Asynchronous Magnetic Bead Rotation (AMBR) Microviscometer for Label-Free DNA Analysis.

We have developed a label-free viscosity-based DNA detection system, using paramagnetic beads as an asynchronous magnetic bead rotation (AMBR) microviscometer. We have demonstrated experimentally that the bead rotation period is linearly proportional to the viscosity of a DNA solution surrounding the paramagnetic bead, as expected theoretically. Simple optical measurement of asynchronous microbead motion determines solution viscosity precisely in microscale volumes, thus allowing an estimate of DNA concentration or average fragment length.

Super-resolution imaging of PDMS nanochannels by single-molecule micelle-assisted blink microscopy.

Single-molecule super-resolution microscopy is an emerging technique for nanometer-scale fluorescence imaging, but in vitro single-molecule imaging protocols typically require a constant supply of reagents, and such transport is restricted in constrained geometries. In this article, we develop single-molecule micelle-assisted blink (MAB) microcopy to enable subdiffraction-limit imaging of nanochannels with better than 40 nm accuracy. The method, based on micelles and thiol-related photoswitching, is used to measure nanochannels formed in polydimethylsiloxane through tensile cracking.

Nanoliter droplet viscometer with additive-free operation.

Measurement of a solution's viscosity is an important analytic technique for a variety of applications including medical diagnosis, pharmaceutical development, and industrial processing. The use of droplet-based (e.g.

Asynchronous magnetic bead rotation microviscometer for rapid, sensitive, and label-free studies of bacterial growth and drug sensitivity.

The long turnaround time in antimicrobial susceptibility testing (AST) endangers patients and encourages the administration of wide spectrum antibiotics, thus resulting in alarming increases of multidrug resistant pathogens. A method for faster detection of bacterial proliferation presents one avenue toward addressing this global concern. We report on a label-free asynchronous magnetic bead rotation (AMBR) based viscometry method that rapidly detects bacterial growth and determines drug sensitivity by measuring changes in the suspension's viscosity.

Active control of nanolitre droplet contents with convective concentration gradients across permeable walls.

Nanolitre droplets in microfluidic devices can be used to perform thousands of independent chemical and biological experiments while minimizing reagents, cost and time. However, the absence of simple and versatile methods capable of controlling the contents of these nanolitre chemical systems limits their scientific potential. To address this, we have developed a method that is simple to fabricate and can continuously control nanolitre chemical systems by integrating a time-resolved convective flow signal across a permeable membrane wall.

Next-generation integrated microfluidic circuits.

This mini-review provides a brief overview of recent devices that use networks of elastomeric valves to minimize or eliminate the need for interconnections between microfluidic chips and external instruction lines that send flow control signals. Conventional microfluidic control mechanisms convey instruction signals in a parallel manner such that the number of instruction lines must increase as the number of independently operated valves increases. The devices described here circumvent this "tyranny of microfluidic interconnects" by the serial encoding of information to enable instruction of an arbitrary number of independent valves with a set number of control lines, or by the microfluidic circuit-embedded encoding of instructions to eliminate control lines altogether.

Asynchronous magnetic bead rotation (AMBR) biosensor in microfluidic droplets for rapid bacterial growth and susceptibility measurements.

Inappropriate antibiotic use is a major factor contributing to the emergence and spread of antimicrobial resistance. The long turnaround time (over 24 hours) required for clinical antimicrobial susceptibility testing (AST) often results in patients being prescribed empiric therapies, which may be inadequate, inappropriate, or overly broad-spectrum. A reduction in the AST time may enable more appropriate therapies to be prescribed earlier.

Push-pull perfusion sampling with segmented flow for high temporal and spatial resolution in vivo chemical monitoring.

Low-flow push-pull perfusion is a sampling method that yields better spatial resolution than competitive methods like microdialysis. Because of the low flow rates used (50 nL/min), it is challenging to use this technique at high temporal resolution which requires methods of collecting, manipulating, and analyzing nanoliter samples. High temporal resolution also requires control of Taylor dispersion during sampling.

Flexible casting of modular self-aligning microfluidic assembly blocks.

The recent shift among developers of microfluidic technologies toward modularized "plug and play" construction reflects the steadily increasing realization that, for many would-be users of microfluidic tools, traditional clean-room microfabrication is prohibitively complex and/or expensive. In this work, we present an advanced modular microfluidic construction scheme in which pre-fabricated microfluidic assembly blocks (MABs) can be quickly fashioned, without expertise or specialized facilities, into sophisticated microfluidic devices for a wide range of applications. Specifically, we describe three major advances to the MAB concept: (1) rapid production and extraction of MABs using flexible casting trays, (2) use of pre-coated substrates for simultaneous assembly and bonding, and (3) modification of block design to include automatic alignment and sealing structures.