Shawn Mulvaney | U.S. Naval Research Laboratory (original) (raw)
Papers by Shawn Mulvaney
Sensors and Bio-Sensing Research, 2018
Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide... more Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide. Since fevers can arise from a wide range of diseases, identifying the causative pathogen is essential not only for effective personal treatment but also for early detection of outbreaks. The Defense Threat Reduction Agency (DTRA) tasked a coalition of commercial, academic, and government researchers with moving diagnostic technology concepts from ideation to field use as rapidly as possible using scientifically sound evaluations. DTRA’s 24 Month Challenge program examined more than 30 technologies before fielding four technologies on four continents. More than 10,000 in field test results were recorded. Here we discuss our tiered evaluation system to assess candidate technologies developed by commercial partners and the process of field testing those technologies at various front-line clinics in Sierra Leone, Thailand, Peru, and Australia. We discuss successes and challenges for introducing two multiplexed lateral flow immunoassay (LFI) tests that detect malaria, dengue fever, melioidosis, and the plague. Additionally we discuss the use of a LFI reader that assisted the interpretation of the assay, communicated results to a data cloud, and greatly facilitated reach-back support. Lastly, we discuss the concurrent field testing of a multiplexed PCR assay on the FilmArray platform, which had an assay pouch specially designed for the 24 Month Challenge. Either standard-of-care or gold-standard testing were run alongside our fielded technologies to benchmark their performance.
BioTechniques, 2004
Microbeads that are both paramagnetic and fluorescently labeled are commercially available in col... more Microbeads that are both paramagnetic and fluorescently labeled are commercially available in colors spanning the visible spectrum. Although these commercial beads can be bright, polydispersity in both size and fluorescent intensity limit their use in quantitative assays. Very recently, more monodisperse beads have become available, but their large size and surface properties make them less than ideal for some bioassay applications. Here we describe methods to customize commercial nonfluorescent magnetic microparticles with fluorescent dyes and quantum dots (QDs) without affecting their magnetic or surface chemical properties. Fluorescent dyes and 3.3-nm diameter CdSe/ZnS QDs were sequestered within 0.8-micron diameter magnetic beads by swelling the polystyrene matrix of the bead in organic solvent, letting the chromophores partition, and then collapsing the matrix in polar solvents. Chromophore incorporation has been characterized using both UV-visible absorption spectroscopy and f...
Nature Nanotechnology, 2011
Langmuir, Apr 11, 2003
... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . De... more ... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and Nanoplex Technologies Inc ...
This document details the microscope configuration, data analysis calculations and derivations, f... more This document details the microscope configuration, data analysis calculations and derivations, finite element simulations, dipole approximation modeling and control studies.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2009
Amongst the plethora of affinity biosensor systems based on biomolecular recognition and labeling... more Amongst the plethora of affinity biosensor systems based on biomolecular recognition and labeling assays, magnetic labeling and detection has emerged as a promising approach. Magnetic labels can be detected by a wide range of non-invasive methods, are physically and chemically stable, relatively inexpensive to produce, and can be easily made biocompatible. Over a decade ago, the U. S. Naval Research Laboratory pioneered the use of giant magnetoresistive (GMR) sensors to detect biomolecules labeled with paramagnetic microbeads. Since then, our various investigations and engineering efforts have resulted in significant improvements in both the magnetoelectronic instrumentation and the assays associated with these magnetic labels. This paper and subsequent presentation provides a synopsis of the development of our technology which has evolved into a highly sensitive detection method.
Frontiers in Pathogen Detection: From Nanosensors to Systems, 2009
Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and s... more Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and shellfish harvesting, crop irrigation, and human consumption. The need for water monitoring becomes more pronounced when industrial, agricultural, and residential lands are found in close proximity. Fecal contamination is particularly problematic and identification of the pollution source essential to remediation efforts. Standard monitoring for fecal contamination
Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and s... more Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and shellfish harvesting, crop irrigation, and human consumption. The need for water monitoring becomes more pronounced when industrial, agricultural, and residential lands are found in close proximity. Fecal contamination is particularly problematic and identification of the pollution source essential to remediation efforts. Standard monitoring for fecal contamination
ACS Nano, 2014
The world is filled with widely varying chemical, physical, and biological stimuli. Over millenni... more The world is filled with widely varying chemical, physical, and biological stimuli. Over millennia, organisms have refined their senses to cope with these diverse stimuli, becoming virtuosos in differentiating closely related antigens, handling extremes in concentration, resetting the spent sensing mechanisms, and processing the multiple data streams being generated. Nature successfully deals with both repeating and new stimuli, demonstrating great adaptability when confronted with the latter. Interestingly, nature accomplishes these feats using a fairly simple toolbox. The sensors community continues to draw inspiration from nature's example: just look at the antibodies used as biosensor capture agents or the neural networks that process multivariate data streams. Indeed, many successful sensors have been built by simply mimicking natural systems. However, some of the most exciting breakthroughs occur when the community moves beyond mimicking nature and learns to use nature's tools in innovative ways.
Carbon, 2015
ABSTRACT Graphene (Gr)–polystyrene (PS) and graphene (Gr)–ultra-high molecular weight polyethylen... more ABSTRACT Graphene (Gr)–polystyrene (PS) and graphene (Gr)–ultra-high molecular weight polyethylene (UHMW PE) laminates were fabricated using a transfer print approach that relies on differential adhesion to remove graphene from Cu foil without chemical etching. The polymer surfaces were prepared using plasma functionalization followed by N-ethylamino-4-azidotetrafluorobenzoate (TFPA) deposition. Then, the graphene on Cu foil and the TFPA coated polymers were pressed at elevated temperature and mild pressure. Finally, they were separated by mechanical peeling. No additional processing was applied. Detailed chemical, structural, and morphological characterization of PS and UHMW PE before and after graphene transfer print was performed using a suite of complementary surface analysis techniques including X-ray Photoelectron Spectroscopy (XPS), Near Edge X-ray Absorption Fine Structure Spectroscopy (NEXAFS), Raman Spectroscopy, and Atomic Force Microscopy (AFM). The charge carrier density and charge carrier mobility of the transferred graphene were determined using Hall effect measurements. We found that graphene’s electrical properties were preserved and comparable to those of graphene on SiO2/Si. Furthermore, modulation of TFPA attachment to PS and UHMW PE led to different TFPA-layer microstructure and therefore to a different amount of functional azide groups available to form carbene bonds with graphene causing changes in graphene’s compressive strain, doping and mobility.
ACS Symposium Series, 2000
Surface enhanced Raman scattering (SERS) has the potential to be an ultrasensitive technique for ... more Surface enhanced Raman scattering (SERS) has the potential to be an ultrasensitive technique for environmental analysis. Highly enhancing SERS substrates assembled by evaporation of a thin Ag film over a Ag-coated, colloidal Au submonolayer have been ...
BioTechniques, 2014
Thin spun-coat films (~4 nm thick) of graphene oxide (GO) constitute a versatile surface chemistr... more Thin spun-coat films (~4 nm thick) of graphene oxide (GO) constitute a versatile surface chemistry compatible with a broad range of technologically important sensor materials. Countless publications are dedicated to the nuances of surface chemistries that have been developed for sensors, with almost every material having unique characteristics. There would be enormous value in a surface chemistry that could be applied generally with functionalization and passivation already optimized regardless of the sensor material it covered. Such a film would need to be thin, conformal, and allow for multiple routes toward covalent linkages. It is also vital that the film permit the underlying sensor to transduce. Here we show that GO films can be applied over a diverse set of sensor surfaces, can link biomolecules through multiple reaction pathways, and can support cell growth. Application of a graphene veil atop a magnetic sensor array is demonstrated with an immunoassay. We also present biose...
Analytical Chemistry, 1998
Nano Letters, 2012
In this paper we demonstrate high-quality, uniform dry transfer of graphene grown by chemical vap... more In this paper we demonstrate high-quality, uniform dry transfer of graphene grown by chemical vapor deposition on copper foil to polystyrene. The dry transfer exploits an azide linker molecule to establish a covalent bond to graphene and to generate greater graphene-polymer adhesion compared to that of the graphene-metal foil. Thus, this transfer approach provides a novel alternative route for graphene transfer, which allows for the metal foils to be reused.
Marine Drugs, 2010
Tetrodotoxin (TTX) is a low molecular weight (~319 Da) neurotoxin found in a number of animal spe... more Tetrodotoxin (TTX) is a low molecular weight (~319 Da) neurotoxin found in a number of animal species, including pufferfish. Protection from toxin tainted food stuffs requires rapid, sensitive, and specific diagnostic tests. An emerging technique for the detection of both proteins and nucleic acids is Fluidic Force Discrimination (FFD) assays. This simple and rapid method typically uses a sandwich immunoassay format labeled with micrometer-diameter beads and has the novel capability of removing nonspecifically attached beads under controlled, fluidic conditions. This technique allows for near realtime, multiplexed analysis at levels of detection that exceed many of the conventional transduction methods (e.g., ELISAs). In addition, the large linear dynamic range afforded by FFD should decrease the need to perform multiple sample dilutions, a common challenge for food testing. By applying FFD assays to an inhibition immunoassay platform specific for TTX and transduction via low magnification microscopy, levels of detection of ~15 ng/mL and linear dynamic ranges of 4 to 5 orders of magnitude were achieved. The results from these studies on the first small molecule FFD assay, along with the impact to detection of seafood toxins, will be discussed in this manuscript.
Langmuir, 2007
Silicon nitride is the most commonly used passivation layer in biosensor applications where elect... more Silicon nitride is the most commonly used passivation layer in biosensor applications where electronic components must be interfaced with ionic solutions. Unfortunately, the predominant method for functionalizing silicon nitride surfaces, silane chemistry, suffers from a lack of reproducibility. As an alternative, we have developed a silane-free pathway that allows for the direct functionalization of silicon nitride through the creation of primary amines formed by exposure to a radio frequency glow discharge plasma fed with humidified air. The aminated surfaces can then be further functionalized by a variety of methods; here we demonstrate using glutaraldehyde as a bifunctional linker to attach a robust NeutrAvidin (NA) protein layer. Optimal amine formation, based on plasma exposure time, was determined by labeling treated surfaces with an amine-specific fluorinated probe and characterizing the coverage using X-ray photoelectron spectroscopy (XPS). XPS and radiolabeling studies also reveal that plasma-modified surfaces, as compared with silane-modified surfaces, result in similar NA surface coverage, but notably better reproducibility.
Langmuir, 2003
... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . De... more ... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and Nanoplex Technologies Inc ...
Lab on a Chip, 2009
We have developed a universal structure and mechanism for the repeatable, rapid-attachment of a f... more We have developed a universal structure and mechanism for the repeatable, rapid-attachment of a fluid cell to a planar substrate. The fluid cell and all fluidic connections are completely contained in a plastic body such that attachment requires neither adhesives nor modification of the substrate. The geometry of the fluid cell is defined by the active area of the planar substrate (e.g. a sensor array). All required components have been quickly prototyped using Computer Numerical Control (CNC) machining. It is also straight-forward to create an array of fluid cells to attach to a single substrate (e.g. a standard microscope slide). All components are easy to assemble and can be cleaned and reused, making this flexible approach applicable for a wide range of lab-on-a-chip applications.
Sensors and Bio-Sensing Research, 2018
Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide... more Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide. Since fevers can arise from a wide range of diseases, identifying the causative pathogen is essential not only for effective personal treatment but also for early detection of outbreaks. The Defense Threat Reduction Agency (DTRA) tasked a coalition of commercial, academic, and government researchers with moving diagnostic technology concepts from ideation to field use as rapidly as possible using scientifically sound evaluations. DTRA’s 24 Month Challenge program examined more than 30 technologies before fielding four technologies on four continents. More than 10,000 in field test results were recorded. Here we discuss our tiered evaluation system to assess candidate technologies developed by commercial partners and the process of field testing those technologies at various front-line clinics in Sierra Leone, Thailand, Peru, and Australia. We discuss successes and challenges for introducing two multiplexed lateral flow immunoassay (LFI) tests that detect malaria, dengue fever, melioidosis, and the plague. Additionally we discuss the use of a LFI reader that assisted the interpretation of the assay, communicated results to a data cloud, and greatly facilitated reach-back support. Lastly, we discuss the concurrent field testing of a multiplexed PCR assay on the FilmArray platform, which had an assay pouch specially designed for the 24 Month Challenge. Either standard-of-care or gold-standard testing were run alongside our fielded technologies to benchmark their performance.
BioTechniques, 2004
Microbeads that are both paramagnetic and fluorescently labeled are commercially available in col... more Microbeads that are both paramagnetic and fluorescently labeled are commercially available in colors spanning the visible spectrum. Although these commercial beads can be bright, polydispersity in both size and fluorescent intensity limit their use in quantitative assays. Very recently, more monodisperse beads have become available, but their large size and surface properties make them less than ideal for some bioassay applications. Here we describe methods to customize commercial nonfluorescent magnetic microparticles with fluorescent dyes and quantum dots (QDs) without affecting their magnetic or surface chemical properties. Fluorescent dyes and 3.3-nm diameter CdSe/ZnS QDs were sequestered within 0.8-micron diameter magnetic beads by swelling the polystyrene matrix of the bead in organic solvent, letting the chromophores partition, and then collapsing the matrix in polar solvents. Chromophore incorporation has been characterized using both UV-visible absorption spectroscopy and f...
Nature Nanotechnology, 2011
Langmuir, Apr 11, 2003
... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . De... more ... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and Nanoplex Technologies Inc ...
This document details the microscope configuration, data analysis calculations and derivations, f... more This document details the microscope configuration, data analysis calculations and derivations, finite element simulations, dipole approximation modeling and control studies.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2009
Amongst the plethora of affinity biosensor systems based on biomolecular recognition and labeling... more Amongst the plethora of affinity biosensor systems based on biomolecular recognition and labeling assays, magnetic labeling and detection has emerged as a promising approach. Magnetic labels can be detected by a wide range of non-invasive methods, are physically and chemically stable, relatively inexpensive to produce, and can be easily made biocompatible. Over a decade ago, the U. S. Naval Research Laboratory pioneered the use of giant magnetoresistive (GMR) sensors to detect biomolecules labeled with paramagnetic microbeads. Since then, our various investigations and engineering efforts have resulted in significant improvements in both the magnetoelectronic instrumentation and the assays associated with these magnetic labels. This paper and subsequent presentation provides a synopsis of the development of our technology which has evolved into a highly sensitive detection method.
Frontiers in Pathogen Detection: From Nanosensors to Systems, 2009
Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and s... more Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and shellfish harvesting, crop irrigation, and human consumption. The need for water monitoring becomes more pronounced when industrial, agricultural, and residential lands are found in close proximity. Fecal contamination is particularly problematic and identification of the pollution source essential to remediation efforts. Standard monitoring for fecal contamination
Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and s... more Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and shellfish harvesting, crop irrigation, and human consumption. The need for water monitoring becomes more pronounced when industrial, agricultural, and residential lands are found in close proximity. Fecal contamination is particularly problematic and identification of the pollution source essential to remediation efforts. Standard monitoring for fecal contamination
ACS Nano, 2014
The world is filled with widely varying chemical, physical, and biological stimuli. Over millenni... more The world is filled with widely varying chemical, physical, and biological stimuli. Over millennia, organisms have refined their senses to cope with these diverse stimuli, becoming virtuosos in differentiating closely related antigens, handling extremes in concentration, resetting the spent sensing mechanisms, and processing the multiple data streams being generated. Nature successfully deals with both repeating and new stimuli, demonstrating great adaptability when confronted with the latter. Interestingly, nature accomplishes these feats using a fairly simple toolbox. The sensors community continues to draw inspiration from nature's example: just look at the antibodies used as biosensor capture agents or the neural networks that process multivariate data streams. Indeed, many successful sensors have been built by simply mimicking natural systems. However, some of the most exciting breakthroughs occur when the community moves beyond mimicking nature and learns to use nature's tools in innovative ways.
Carbon, 2015
ABSTRACT Graphene (Gr)–polystyrene (PS) and graphene (Gr)–ultra-high molecular weight polyethylen... more ABSTRACT Graphene (Gr)–polystyrene (PS) and graphene (Gr)–ultra-high molecular weight polyethylene (UHMW PE) laminates were fabricated using a transfer print approach that relies on differential adhesion to remove graphene from Cu foil without chemical etching. The polymer surfaces were prepared using plasma functionalization followed by N-ethylamino-4-azidotetrafluorobenzoate (TFPA) deposition. Then, the graphene on Cu foil and the TFPA coated polymers were pressed at elevated temperature and mild pressure. Finally, they were separated by mechanical peeling. No additional processing was applied. Detailed chemical, structural, and morphological characterization of PS and UHMW PE before and after graphene transfer print was performed using a suite of complementary surface analysis techniques including X-ray Photoelectron Spectroscopy (XPS), Near Edge X-ray Absorption Fine Structure Spectroscopy (NEXAFS), Raman Spectroscopy, and Atomic Force Microscopy (AFM). The charge carrier density and charge carrier mobility of the transferred graphene were determined using Hall effect measurements. We found that graphene’s electrical properties were preserved and comparable to those of graphene on SiO2/Si. Furthermore, modulation of TFPA attachment to PS and UHMW PE led to different TFPA-layer microstructure and therefore to a different amount of functional azide groups available to form carbene bonds with graphene causing changes in graphene’s compressive strain, doping and mobility.
ACS Symposium Series, 2000
Surface enhanced Raman scattering (SERS) has the potential to be an ultrasensitive technique for ... more Surface enhanced Raman scattering (SERS) has the potential to be an ultrasensitive technique for environmental analysis. Highly enhancing SERS substrates assembled by evaporation of a thin Ag film over a Ag-coated, colloidal Au submonolayer have been ...
BioTechniques, 2014
Thin spun-coat films (~4 nm thick) of graphene oxide (GO) constitute a versatile surface chemistr... more Thin spun-coat films (~4 nm thick) of graphene oxide (GO) constitute a versatile surface chemistry compatible with a broad range of technologically important sensor materials. Countless publications are dedicated to the nuances of surface chemistries that have been developed for sensors, with almost every material having unique characteristics. There would be enormous value in a surface chemistry that could be applied generally with functionalization and passivation already optimized regardless of the sensor material it covered. Such a film would need to be thin, conformal, and allow for multiple routes toward covalent linkages. It is also vital that the film permit the underlying sensor to transduce. Here we show that GO films can be applied over a diverse set of sensor surfaces, can link biomolecules through multiple reaction pathways, and can support cell growth. Application of a graphene veil atop a magnetic sensor array is demonstrated with an immunoassay. We also present biose...
Analytical Chemistry, 1998
Nano Letters, 2012
In this paper we demonstrate high-quality, uniform dry transfer of graphene grown by chemical vap... more In this paper we demonstrate high-quality, uniform dry transfer of graphene grown by chemical vapor deposition on copper foil to polystyrene. The dry transfer exploits an azide linker molecule to establish a covalent bond to graphene and to generate greater graphene-polymer adhesion compared to that of the graphene-metal foil. Thus, this transfer approach provides a novel alternative route for graphene transfer, which allows for the metal foils to be reused.
Marine Drugs, 2010
Tetrodotoxin (TTX) is a low molecular weight (~319 Da) neurotoxin found in a number of animal spe... more Tetrodotoxin (TTX) is a low molecular weight (~319 Da) neurotoxin found in a number of animal species, including pufferfish. Protection from toxin tainted food stuffs requires rapid, sensitive, and specific diagnostic tests. An emerging technique for the detection of both proteins and nucleic acids is Fluidic Force Discrimination (FFD) assays. This simple and rapid method typically uses a sandwich immunoassay format labeled with micrometer-diameter beads and has the novel capability of removing nonspecifically attached beads under controlled, fluidic conditions. This technique allows for near realtime, multiplexed analysis at levels of detection that exceed many of the conventional transduction methods (e.g., ELISAs). In addition, the large linear dynamic range afforded by FFD should decrease the need to perform multiple sample dilutions, a common challenge for food testing. By applying FFD assays to an inhibition immunoassay platform specific for TTX and transduction via low magnification microscopy, levels of detection of ~15 ng/mL and linear dynamic ranges of 4 to 5 orders of magnitude were achieved. The results from these studies on the first small molecule FFD assay, along with the impact to detection of seafood toxins, will be discussed in this manuscript.
Langmuir, 2007
Silicon nitride is the most commonly used passivation layer in biosensor applications where elect... more Silicon nitride is the most commonly used passivation layer in biosensor applications where electronic components must be interfaced with ionic solutions. Unfortunately, the predominant method for functionalizing silicon nitride surfaces, silane chemistry, suffers from a lack of reproducibility. As an alternative, we have developed a silane-free pathway that allows for the direct functionalization of silicon nitride through the creation of primary amines formed by exposure to a radio frequency glow discharge plasma fed with humidified air. The aminated surfaces can then be further functionalized by a variety of methods; here we demonstrate using glutaraldehyde as a bifunctional linker to attach a robust NeutrAvidin (NA) protein layer. Optimal amine formation, based on plasma exposure time, was determined by labeling treated surfaces with an amine-specific fluorinated probe and characterizing the coverage using X-ray photoelectron spectroscopy (XPS). XPS and radiolabeling studies also reveal that plasma-modified surfaces, as compared with silane-modified surfaces, result in similar NA surface coverage, but notably better reproducibility.
Langmuir, 2003
... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . De... more ... Shawn P. Mulvaney,* Michael D. Musick, Christine D. Keating, and Michael J. Natan . Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and Nanoplex Technologies Inc ...
Lab on a Chip, 2009
We have developed a universal structure and mechanism for the repeatable, rapid-attachment of a f... more We have developed a universal structure and mechanism for the repeatable, rapid-attachment of a fluid cell to a planar substrate. The fluid cell and all fluidic connections are completely contained in a plastic body such that attachment requires neither adhesives nor modification of the substrate. The geometry of the fluid cell is defined by the active area of the planar substrate (e.g. a sensor array). All required components have been quickly prototyped using Computer Numerical Control (CNC) machining. It is also straight-forward to create an array of fluid cells to attach to a single substrate (e.g. a standard microscope slide). All components are easy to assemble and can be cleaned and reused, making this flexible approach applicable for a wide range of lab-on-a-chip applications.