Paul Yager

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Papers by Paul Yager

A rapid, instrument-free, sample-to-result nucleic acid amplification test

Lab on a Chip, 2016

This diagnostic system prototype is the first demonstration of a fully integrated, simple-to-use ... more

A low cost point-of-care viscous sample preparation device for molecular diagnosis in the developing world; an example of microfluidic origami

Lab Chip, 2012

The lab-on-a-chip concept has led to several point-of-care (POC) diagnostic microfluidic platform... more The lab-on-a-chip concept has led to several point-of-care (POC) diagnostic microfluidic platforms. However, few of these can process raw samples for molecular diagnosis and fewer yet are suited for use in a resource-limited setting without permanent electrical infrastructure. We present here a very low cost paper microfluidic device for POC extraction of bacterial DNA from raw viscous samples--a challenge for conventional microfluidic platforms. This is an example of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;microfluidic origami&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; in that the system is activated by folding; demonstrated here is room temperature cell lysis and DNA extraction from pig mucin (simulating sputum) spiked with E. coli without the use of external power. The microfluidic origami device features dry reagent storage and rehydration of the lysis buffer. We demonstrate DNA extraction from samples with a bacterial load as low as 33 CFU ml(-1). Extraction times, starting from the raw sample, have been optimized to about 1.5 h without the use of external power, or to within 1 h using an oven or a heater block. The fabrication of this paper microfluidic device can be translated into high volume production in the developing world without the need for a semiconductor clean room or a microfabrication facility. The sample preparation can be performed with the addition of just the sample, water, ethanol and elute buffer to the device, thus reducing chemical hazards during transport and handling.

Point-Of-Care Immunoassay Cards for Sample-To-Result Differential Diagnosis of Acute Fever

We present air-driven microfluidic cards that perform sample processing and parallel immunoassays... more We present air-driven microfluidic cards that perform sample processing and parallel immunoassays for antigens and IgM antibodies. The disposable cards are based on a flow-through membrane immunoassay carried out on porous nitrocellulose, which provides rapid diffusion for short assay times and a high surface area for visual detection. Malarial antigen, Plasmodium falciparum HRPII antigen, showed a limit of detection of 20-30 ng/mL spiked into fetal bovine serum. Detection of IgM antibodies to Salmonella Typhi, from clinical plasma samples, correlated closely with bench-top tests. All reagents were stored dried on card; only sample and buffer were required to run the test.

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Patterned Sol-Gel Structures by Micro Molding in Capillaries

MRS Proceedings, 1996

The development of a variety of micro-optical chemical sensor and biosensor devices will rely on ... more The development of a variety of micro-optical chemical sensor and biosensor devices will rely on an ability to fabricate and effectively pattern physically and chemically sensitive materials. Toward this end, organically modified sol-gel materials are patterned onto a substrate using a benign technique called micro molding in capillaries (MIMIC). Closely spaced, organically modified silica ridges containing organic dyes are demonstrated. The mold consists of a micro channel-filled elastomeric master in contact with a glass substrate. Liquid sols fill the mold as a result of capillary action. A reservoir-channel system in the mold allows simultaneous casting of sols with different chemical compositions. After gelation, the elastomeric master is removed and sol-gel structures are left on the substrate. Cross-sectional dimensions of the ridges range from one to tens of micrometers, and can be centimeters in length. Because of the mild processing conditions, the method is especially att...

Enabling lateral transport of genomic DNA through porous membranes for point-of-care applications

Anal. Methods, 2017

Simultaneous cell lysis and DNA fragmentation to allow for controllable lateral transport of DNA ... more

Transverse Transport in Microsystems

Separation Methods In Microanalytical Systems, 2005

A novel method of fluorescence detection and spectroscopy

Electric Field Manipulation of Phospholipid Tubules: Optical Birefringence Measurements

Molecular Crystals and Liquid Crystals Incorporating Nonlinear Optics, 1989

Abstract The polymerizable phospholipid DC23PC forms straight, hollow cylinders in water. Using a... more Abstract The polymerizable phospholipid DC23PC forms straight, hollow cylinders in water. Using ac electric fields it is possible to achieve significant orientation of these structures. A birefringence method was used to obtain the effective electric susceptibility anisotropy ΔχE, the value of which is in good agreement with that obtained earlier from light scattering measurements.

<title>Fiber optic sensor for general anesthetics based on Raman spectroscopy</title>

Biomedical Fiber Optic Instrumentation, 1994

Vibrational spectroscopy and chemometrics together can be used to identify and quantify low conce... more Vibrational spectroscopy and chemometrics together can be used to identify and quantify low concentrations of small molecules, but the Raman effect has been considered too weak to be employed for remote fiber optic sensing of such gases. Preliminary data are presented suggesting that it is possible to enhance Raman signals of gases from a small probe. Polymers that have large partition coefficients for small nonpolar molecules such as general anesthetics can be used as selective absorbents for these gases. As long as the polymers do not luminesce or Raman scatter at interfering frequencies, they increase the signal-to-noise ratio of signals from absorbed molecules. Multipass cells are often used to enhance Raman scattering from gases. Forming an absorbent polymer into a ring with one or more optical `taps' allows recirculation of the excitation light, and extraction of the contrarotating Raman scattered light. Such a ring could be the basis of a small probe to be connected to a compact Raman instrument by optical fibers. These two methods of amplification improve signal-to-noise ratio, extend sensing range, and reduce both instrumental complexity and cost of sensors.

On-chip detection of myoglobin based on fluorescence

Biosensors and Bioelectronics, 2009

A disposable immunosensor cartridge was developed that allows antibodies to be immobilized on the... more A disposable immunosensor cartridge was developed that allows antibodies to be immobilized on the surface for the detection of myoglobin, a marker for the early assessment of acute myocardial infarction (AMI) using fluorescence techniques. The anti-myoglobin antibody was immobilized on a polystyrene substrate based on covalent bonding via silanization. The immunosensor chip layers were fabricated from sheets by CO(2)-laser ablation. The functionalized polystyrene surfaces were characterized by contact angle measurement, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). After the antigen-antibody reaction as a sandwich enzyme-linked immunosorbent assay (ELISA) with a horseradish peroxidase-conjugated secondary antibody (HRP-anti-myoglobin), addition of fluorogenic substrate produced a fluorescent dye which was quantified on-chip using fluorescent technique. The immunosensor response was linear for myoglobin concentrations between 20 and 230 ng/ml (r=0.991, n=3). The detection limit was found to be 16 ng/ml, which is lower than the clinical cut-off value for myoglobin in healthy patients. This protocol could be extended to the detection of other important cardiac markers simultaneously in microchannels.

Biotechnology at low Reynolds numbers

Biophysical Journal, 1996

The shrinking of liquid handling systems to the micron and submicron size range entails moving in... more The shrinking of liquid handling systems to the micron and submicron size range entails moving into the area of small Reynolds numbers. The fluid dynamics in this regime are very different from the macroscale. We present an intuitive explanation of how the different physics of small Reynolds numbers flow, along with microscopic sizes, can influence device design, and give examples from our own work using fluid flow in microfabricated devices designed for biological processing.

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Order in Diacetylenic Microstructures

Molecular Crystals and Liquid Crystals Incorporating Nonlinear Optics, 1987

ABSTRACT

Medical Biosensors

Biomaterials Science, 2013

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Imaging of Surfaces by Concurrent Surface Plasmon Resonance and Surface Plasmon Resonance-Enhanced Fluorescence

PLoS ONE, 2010

Surface plasmon resonance imaging and surface plasmon induced fluorescent are sensitive tools for... more Surface plasmon resonance imaging and surface plasmon induced fluorescent are sensitive tools for surface analysis. However, existing instruments in this area have provided limited capability for concurrent detection, and may be large and expensive. We demonstrate a highly cost-effective system capable of concurrent surface plasmon resonance microscopy (SPRM) and surface plasmon resonance-enhanced fluorescence (SPRF) imaging, allowing for simultaneous monitoring of reflectivity and fluorescence from discrete spatial regions. The instrument allows for high performance imaging and quantitative measurements with surface plasmon resonance, and surface plasmon induced fluorescence, with inexpensive off-the-shelf components.

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The evolution of nitrocellulose as a material for bioassays

MRS Bulletin, 2013

The Photovoltaic Materials and Manufacturing Issues III Workshop (PVIII), the third in a series o... more The Photovoltaic Materials and Manufacturing Issues III Workshop (PVIII), the third in a series organized by MRS, is the premier forum on new challenges in PV materials and manufacturing. The three-day workshop will discuss major issues pertaining to current and emerging materials for PV, low-cost production of solar cells and modules, and next-generation solar cells capable of reaching even higher efficiencies. The workshop will feature a combination of oral and review presentations by invited speakers, poster sessions, and discussion sessons. WORKSHOP TOPICS INCLUDE All research aspects related to current materials and solar cells, including single-crystal and multicrystalline silicon, amorphous/ microcrystalline silicon, CdTe, and CIGS. In particular: material and device properties; device modeling; deposition techniques; defects and impurities and their influence on the device performance; relevant materials and process modifications to improve device quality (efficiency and stability) Approaches for commercial production, with focus on precursor and feedstock materials, module design and processing, advances in innovative device fabrication methods New materials for PV applications such as organic, quantum dots, thin-film Si New module designs, materials, technologies, and module reliability issues Advanced measurement/characterization methods, and instrumentation for in-situ measurements, defect monitoring and process control; performance, reliability testing and standards

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Zero-order interfacial enzymatic degradation of phospholipid tubules

Biophysical Journal, 1997

The first study of enzymatic hydrolysis of phospholipid tubules is reported. Phosphatidylcholines... more The first study of enzymatic hydrolysis of phospholipid tubules is reported. Phosphatidylcholines with acyl chains containing diacetylene groups are known to form tubular microstructures in which the lipids are tightly packed and crystalline. These tubules can be used to probe the role of microstructural form in the mechanics of interfacial enzymatic degradation by such enzymes as phospholipase A2 (PLA2). Hydrolysis by PLA2 may occur most rapidly in regions having the greatest number of bilayer packing defects, such as those that must be found at tubule ends. A microstructure that degrades primarily from its ends should exhibit zero-order kinetics, because the area of the degrading tubule end remains constant as the length of the microstructure decreases. Free fatty acid concentration was measured to follow the generation of PLA2 hydrolysis products in suspensions of diacetylenic phospholipid tubules. The kinetics of tubule hydrolysis were essentially zero-order until conversion was complete, as predicted. However, microscopy of partially hydrolyzed tubules revealed the formation of multiple discrete anionic product domains along the length of degrading tubules as well as in insoluble reaction product microstructures. Furthermore, the rate of tubule hydrolysis was only moderately enhanced by increasing the number of tubule ends, which is consistent with the conclusion that tubule ends are not the only sites of hydrolysis. A model that reconciles the overall kinetics with the morphological evidence is proposed.

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A method for characterizing adsorption of flowing solutes to microfluidic device surfaces

Lab Chip, 2007

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Enabling the Development and Deployment of Next Generation Point-of-Care Diagnostics

PLOS Neglected Tropical Diseases, 2015

Plasma separation on chip Shu (Heriot-Watt) Sample preparation Multiwell plates Carrilho (U. Sao ... more

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Automated Analysis of Paper-Based Immunoassay Tests on Mobile Devices

Disease detection in rural areas of low-resource settings is often hampered by a lack of accurate... more Disease detection in rural areas of low-resource settings is often hampered by a lack of accurate, convenient and affordable diagnostic tests. This paper presents research focused on the design and analysis of software used to diagnose immunoassay tests on a mobile device. The tests are paper-based and therefore cheap and appropriate for use in developing regions. Further, the software is simple and intuitive to use and would not require a health worker to have prior training. The developed Android application allows a user to first take a photo of an immunoassay test. The image of the test results is then processed using computer vision algorithms run on the mobile device. The mobile application then produces an objective and automated diagnosis of the immunoassay test at the point of care.

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A Two-Dimensional Paper Network for Comprehesive Dengue Detection at the Point of Care

The two-dimensional paper network (2DPN) is an inexpensive technology based on the strengths of o... more The two-dimensional paper network (2DPN) is an inexpensive technology based on the strengths of one-dimensional lateral flow rapid diagnostic tests. The 2DPN allows complex (bio)chemical processing to be performed without the need for external instrumentation, which is ideally suited to point-of-care testing for infectious disease in low resource settings. We have been exploring the use of 2DPNs for sensitive multiplexed immunoassays. We present progress in the development of 2DPN modules to be used in a multiplexed amplified test for dengue virus proteins and two types of antibodies against them.

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