Perspective on Diagnostics for Global Health

Fu, Elain; Yager, Paul; Floriano, Pierre N.; Christodoulides, Nicolaos; McDevitt, John T.

doi:10.1109/mpul.2011.942766

Cited by 52 publications

(45 citation statements)

References 92 publications

(118 reference statements)

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confidence: 99%

“…[1][2][3] Unfortunately, however, current methods for the detection of such markers are based on either multistep, wash-, or reagentintensive processes and require sophisticated, laboratorybased measurements (e.g., ELISA or Western blot assays) or are at best only semi-quantitative (e.g., immunochemical dipsticks). [4][5][6] These drawbacks limit the accessibility of quantitative molecular diagnostics, resulting in delayed treatment, reduced compliance, and poorer outcomes.…”

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A Modular, DNA‐Based Beacon for Single‐Step Fluorescence Detection of Antibodies and Other Proteins

et al. 2015

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A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformationswitching stem-loop DNA scaffold that presents a smallmolecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors respond rapidly (< 10 min) and selectively, enabling the facile detection of specific proteins even in complex samples, such as blood serum. The versatility of the platform was demonstrated by detecting five bivalent proteins (four antibodies and the chemokine platelet-derived growth factor) and two monovalent proteins (a Fab fragment and the transcription factor TBP) with low nanomolar detection limits and no detectable cross-reactivity.Recent years have seen a significant increase in the number of well-characterized biomarkers, proteins present in the blood or on cells that are diagnostic of disease. [1][2][3] Unfortunately, however, current methods for the detection of such markers are based on either multistep, wash-, or reagentintensive processes and require sophisticated, laboratorybased measurements (e.g., ELISA or Western blot assays) or are at best only semi-quantitative (e.g., immunochemical dipsticks).[4-6] These drawbacks limit the accessibility of quantitative molecular diagnostics, resulting in delayed treatment, reduced compliance, and poorer outcomes. [1,2, 7] In contrast to the cumbersome, multistep nature of current detection schemes, however, biomolecular receptors present in organisms respond to changes in the concentration of their targets in a quantitative fashion and without needing the addition of reagents or wash steps. [8,9] Indeed, these receptors detect thousands of distinct molecules in real time even in the complex in vivo environment.[10] Building artificial biosystems of similar simplicity, convenience, and selectivity represents a major bioengineering goal.One of the strategies used by naturally occurring "sensors" [11] is based on conformational switching in which a receptor undergoes a large-scale, binding-induced conformational change in the presence of its target. [8,9] As their signaling is linked to a specific, binding-induced event, such "switches" are highly selective and enable detection even in highly complex sample matrices.[10] Moreover, such conformational changes can also be harnessed in artificial systems, where they can be used to generate an optical or electrochemical signal without the addition of exogenous reagents or coupling to exogenous biochemical reactions. [12,13] Motivated by these considerations, we have developed a single-step method for the quantitative detection of specific proteins that is rapid, inexpensive, and highly selective. We drew inspiration from DNA molecular beacons, which are synthetic nucleic acid switches for t...

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A Modular, DNA‐Based Beacon for Single‐Step Fluorescence Detection of Antibodies and Other Proteins

et al. 2015

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“…In ongoing work, we are developing next-generation systems that may be suitable for portable testing in the field [i.e., low cost, user friendly, battery-powered, and compact (39 )]. These new designs will likely benefit from the development of low-cost device fabrication methods (29 ), simple instrumentation (30,31 ), and integrated electrochemical sensors (40,41 ).…”

Section: Digital Microfluidic Instrumentationmentioning

confidence: 99%

Digital Microfluidic Platform for the Detection of Rubella Infection and Immunity: A Proof of Concept

Lee

Choi

et al. 2015

Clinical Chemistry

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BACKGROUND:Whereas disease surveillance for infectious diseases such as rubella is important, it is critical to identify pregnant women at risk of passing rubella to their offspring, which can be fatal and can result in congenital rubella syndrome (CRS). The traditional centralized model for diagnosing rubella is cost-prohibitive in resource-limited settings, representing a major obstacle to the prevention of CRS. As a step toward decentralized diagnostic systems, we developed a proof-of-concept digital microfluidic (DMF) diagnostic platform that possesses the flexibility and performance of automated immunoassay platforms used in central facilities, but with a form factor the size of a shoebox.

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“…As the flow-control capabilities of paper microfluidic devices improve, more complex, multi-step assays can be conducted. There is dire need of such low-cost technologies for conducting diagnostic tests in limited resource settings 24 . Currently, automatic multistep tests can only be conducted in expensive instruments, usually only available in sophisticated laboratories.…”

Section: Introductionmentioning

confidence: 99%

A versatile valving toolkit for automating fluidic operations in paper microfluidic devices

et al. 2015

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Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically a) after a certain period of time, or b) after the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods – both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device.

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Perspective on Diagnostics for Global Health

Cited by 52 publications

References 92 publications

A Modular, DNA‐Based Beacon for Single‐Step Fluorescence Detection of Antibodies and Other Proteins

A Modular, DNA‐Based Beacon for Single‐Step Fluorescence Detection of Antibodies and Other Proteins

Digital Microfluidic Platform for the Detection of Rubella Infection and Immunity: A Proof of Concept

A versatile valving toolkit for automating fluidic operations in paper microfluidic devices

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