Paul Yager Research Group
Bioengineering Department, Box 355061, University of Washington, Seattle, WA 98195, USA
Current Research Projects

Note that the following projects were funded as of the date on which this page was updated (see last line of page). This does not guarantee that any of them is funded and active as of the date you read this page, or that if it is still funded, there are extra funds to support you. If you are interested in working on one of these projects, please contact PY's assistant (see Yager's home page). Also, there are projects ongoing at the time that have no external funding, but are progressing nonetheless....

Current Project Title Funding Source
Dates
A high-sensitivity low-cost multiplexed immunoassay platform based on 2-dimensional paper network; demonstration using influenza NIH NIAID

7/11 – 6/16 + NCE

Multiplexable Autonomous Disposables for Nucleic Acid Amplification Tests for Limited Resource Settings (MAD NAAT) DARPA DSO/BTO
9/11 – 11/16

Extending cell phone capabilities for sensitive detection in lateral flow assays

NSF EAGER

9/14 – 8/16 + NCE

EbolaBox

DTRA
4/16-3/18

Return to Yager's Home Page


A high-sensitivity low-cost multiplexed immunoassay platform based on 2-dimensional paper network; demonstration using influenza

A Seattle-based consortium led by the Yager group was awarded $5.7 million in 2011 by the NIAID (an NIH institute). The aim of the 5-year project was to develop a portable device that would increase the sensitivity of protein immunoassays with a combination of using 2DPNs and novel protein binders, with the specific goal of producing a more sensitive assay for influenza.

 

The dual goals of the project were:

1) to increase the sensitivity of the conventional influenza A/B nucleoprotein immunoassay t through chemical amplification of the detection binding event using the HRP-DAB system as implemented by a 2DPN, and

2) to develop novel high-affinity stable protein binders (as an alternative for antibodies) for the HA protein that allow implementation of an HRP-DAB amplified sandwich assay for HA or intact virus on a 2DPN.

A test of a nucleoprotein assay prototype device (see image) for assay of nasal swabs from patients at an ER was carried out at Seattle Children's hospital during the 2015-2016 flu season. The consortium coinvestigators included David Baker of UW's Department of Biochemistry, David Moore of the GE Global Research Center, Elain Fu of UW (now of Oregon State University), Gonzalo Domingo of PATH, and Janet Englund of Seattle Children's.

Top of Page


Multiplexable Autonomous Disposables for Nucleic Acid Amplification Tests for Limited Resource Settings (MAD NAAT)

A Seattle-based consortium led by the Yager group was awarded $19.7 million in 2011 by the DARPA Defense Sciences Office (DSO, later transferred to BTO). The aim of the 5-year project is to develop an instrument-free fully-disposable paper-based diagnostic platform capable of detecting multiple pathogens by their DNA or RNA from a patient sample.

Performance goals for the MAD NAAT device included storage for 1 year at ambient conditions (up to 45°C), incorporation of all reagents on the stored device, and sample-to-result operation within 1 hour.
The readout on the 2015 prototype (shown at left) was on lateral flow strips so that image capture and analysis was possible with a conventional smart phone.

The initial test was to identify MRSA from a nasal swab sample (using DNA), then RSV (using RNA). In the last year of the project the target pathogens were expanded to include Chlamydia trachomatis and Neisseria gonorrhoeae (DNA) in urine and the Zika virus in blood.

The device was to go from sample-to-result anywhere, be simple enough for untrained users, and low enough cost to enable wider use of sophisticated medical tests. Potential high-impact applications are those in which there is a need for significantly improved detection sensitivity to enable earlier diagnosis (and treatment) than is possible with current protein-based tests. These include multiplexed testing for the full range of infectious agents in human and environmental samples.

The consortium coinvestigators includes Barry Lutz of UW Bioengineering, Walt Mahoney of Epoch Biosciences (later the ELITech Group), David Moore of the GE Global Research Center, Bernhard Weigl of PATH, Ferric Fang of UW Laboratory Medicine, and Janet Englund of Seattle Children's.

Top of Page


Extending cell phone capabilities for sensitive detection in lateral flow assays

This is a 2-year NSF EAGER project (a NCE) aimed at utilizing the full potential of current and future smart phones for medical applications, particularly those involving optical detection of biochemical assays. The principal aim was to determine what optical capabilities should be incorporated into the next generation of smart phones to be useful in medical diagnostics tests.

The initial work in the project aimed at determinng if photoacoustic detection of absorbance by gold nanoparticles was a way to increase the sensitivity of lateral flow-based tests for detection of proteins and nucleic acids. The required the use of time-varying light sources of high intensity, and acoustic detectors adjacent to or mechanically coupled to the lateral flow strips, complicating the lateral flow disposable. Ultimately, it was concluded that the light sources would have to be unreasonably bright and expensive to accomplish this goal.

The subsequent work has been aimed at developing methods of combining inexpensive light sources that can be powered by today's smart phones to enhance the sensitivity of lateral flow assays beyond those possible with conventional imaging detection. Initial experiments with quantum dot detection of protein-based bioassays with cell phones have been extremely promising.

Top of Page

 


EbolaBox

In collaboration with the David Baker group, we were awarded $4.3 million in 2016 by the Defense Threat Reduction Agency (DTRA). The aim of the initial 2-year contract is to develop an instrument-free fully-disposable paper-based diagnostic platform capable of extremely sensitive detection of Ebola viral glycoproteins from blood.

{TEM of EBOV, Oct. 13, 1976, by, Frederick A. Murphy of the CDC}

There are three primary goals of this project.

1) Develop a hyper-sensitive protein assay and embody it in a rapid POC disposable format using the 2DPN technology.

2) Develop the molecular tools (novel binding proteins) for capturing and detecting glycoproteins from  Ebolavirus in a sandwich assay on paper.

3) Integrate both technologies into an  disposable that detects EBOV.

If this phase is successful, the goal is to validate the test against DTRA criteria, commercialize and deploy the EbolaBox in an optional follow-on project beginning in year 3 years

 

Top of Page


Return to Yager's Home Page

Return to Research Page

revised 7/03/16