Biophysical Pathogen Identification: a New Paradigm in Diagnosis - - PowerPoint PPT Presentation
Biophysical Pathogen Identification: a New Paradigm in Diagnosis Mark A. Hayes Arizona State University 2015 Image: P . V . Jones Early Pathogen Identification: Impact How do we correctly identify pathogens and their susceptibility early
Mark A. Hayes Arizona State University 2015
Image: P . V . Jones
Wellness Time How do we correctly identify pathogens and their susceptibility early and accurately? Why does it take so long now? What is the best way to move this line from here… …to here …and gain this ‘wellness’?
Fast : allow meaningful action Cheap : cost effective (<$1 per test) Available : widely distributed, low power use, simple operation and readout, etc. Accurate & Precise : sensitive and selective
Symptoms & Sample Culture/Metabolic
CORRECT Identification including susceptibility
Time
Bias Loss No actionable result Culture Negative Phenotype DNA/RNA Susceptibility test Susceptibility test Vetting / Confirmatory
Symptoms & Sample Culture/Metabolic
CORRECT Identification including susceptibility
Time
Bias Loss No actionable result Culture Negative Phenotype DNA/RNA Susceptibility test Lacking DNA/RNA sequence or Immuno Reagent for pathogen Failure to thrive in artificial environment Susceptibility test Vetting / Confirmatory
Symptoms & Sample Culture/Metabolic
CORRECT Identification including susceptibility
Time
Bias Loss No actionable result Culture Negative Phenotype DNA/RNA Susceptibility test Susceptibility test Hyperfine Isolation Vetting / Confirmatory
Symptoms & Sample Culture/Metabolic
CORRECT Identification including susceptibility
Time
Bias Loss No actionable result Culture Negative Phenotype DNA/RNA Susceptibility test Susceptibility test Hyperfine Isolation Confirmatory / Vetting Vetting / Confirmatory
capture of E. coli surface plot
Microfluidic device of simple design and fabrication. Juxtaposes two electric properties of cells & bioparticles: electrophoresis & dielectrophoresis It isolates and concentrates selectively with very high fidelity
http://imgc.allpostersimages.com/images/P-473-488-90/67/6779/W21I100Z/posters/green-light-collection-aerial-view-of-a-harbor-lake-michigan-chicago- cook-county-illinois-usa.jpg
Each slip represents a unique strain and susceptibility There is a possibility of generating millions of biophysically unique ‘slips’
Thanks to Dr. Mclaren for analogy idea
http://imgc.allpostersimages.com/images/P-473-488-90/67/6779/W21I100Z/posters/green-light-collection-aerial-view-of-a-harbor-lake-michigan-chicago- cook-county-illinois-usa.jpg Thanks to Dr. Mclaren for analogy idea : to his credit, he did not stretch it this far!
Anything in the harbor : infection Specific dock : species/strain Specific slip: susceptibility
Traditional techniques usually go: harbor, dock, slip. We can directly address the slip and then compare to known pathogens.
The reason our approach works is hyperfine resolution provided by the high electric fields and gradients afforded in a microdevice.
We operate with extremely intense fields and gradients to maximize the difference in forces on each strain of pathogen.
Desirable Features
& selective)
Aspects to be avoided or minimized
Good
Less Good
Proven Multiple targets Cost Prior molecular knowledge Cold chain Unknown target Costly reagents Culture negative Time
Many categories numerically plotted in easy to see plot. Many other categories could be imagined, these are reasonably representative.
Proven Multiple targets Cost Prior molecular… Cold chain Unknown target Costly reagents Culture negative Time Proven Multiple targets Cost Prior molecular knowledge Cold chain Unknown target Costly reagents Culture negative Time Culture / metabolic DNA/RNA Phenotype
Our Strategy: Current Techniques:
We are in the technology development phase. Red blood cells, viruses, proteins, etc. have been evaluated and published. We have shown extraordinary proof of principle by separating Staphylococcus epidermidis gentamicin resistant and susceptible strains (one enzyme present/absent).
Inlet Outlet
Our theory is completed and published (March 2015) and new high efficiency designs have been modeled and are being fabricated.
storage
current is minimal)
with the fast-evolving smart phone friendly systems
distribution for possible surveillance, within all general practitioners, surgical theaters, and to low resource settings and remote areas.
A new paradigm for identifying pathogens, including susceptibility Based on biophysics and a break-through technology advance in bioparticle separations Compares very favorably to current techniques: faster, cheaper, no bias, compatible with all existing strategies Early in the development cycle– core capabilities theoretical described, seminal data obtained. Looking to make maximum impact on healthcare – for specific patients, reduce disease spread, and reduce healthcare costs.
Continue to develop partnerships with those in the health care business. Identify and pursue funding sources for clinical application, while continuing fundamental studies at ASU.
Katelyn Hayes Paige Davis Shannon Huey Claire Crowther Jie Ding Paul Jones
Funding: “Isolation of Pathogenic Listeria” NIH 2015-2017 “Pathogen Isolation and Concentration for Phenotypic Subtyping” NIH 2012-2014 “Isolating Viral Particles from Whole Blood” NIH 2012-2014