Paper Diagnostic Devices for Electrochemical Detection of Biological Weapons

Richard M. Crooks, PhD, Department of Chemistry, UT Austin
November 20, 2014 6 pm (Food starting at 5:30 pm)
Blum Hall B100

Detection of toxins is of particular importance because near real-time detection is essential in cases of imminent threat and because toxins can be modified or otherwise disguised while remaining active. The objective of this project is the creation of new, low-cost, appropriately sensitive paper diagnostic devices for the electrochemical detection of biological weapons. To satisfy this objective, we initiated development of a quantitative ricin sensor using a magnetic microbead supported silver nanoparticle (AgNP) metalloimmunoassay to probe the ricin A chain protein. The sensor integrates picomolar affinity antibodies with our easily handled, but sophisticated, electrochemical detection platform: the oSlip. The oSlip incorporates two simple, but effective, preconcentration steps. The first involves magnetic preconcentration of AgNP labels at a working electrode, followed by the spontaneous oxidation of these labels in the presence of a chemical oxidant stored on the device. Importantly, this oxidizing agent is delivered into the channel at a specific time and location by simply slipping a moveable piece of paper. The resulting Ag ions are then electrodeposited onto the working electrode (the second preconcentration step). Oxidation of this Ag layer leads to detection of the AgNP-labeled target. We have demonstrated quantitative electrochemical detection of ricn A chain at a LOD of 78 pM by means of fast (3.5 minutes) and non-enzymatic signal amplification. Importantly, the custom antibodies can bind to both glycosylated and recombinant ricin, allowing for the detection of genetically modified toxins. This project is sponsored by the Defense Threat Reduction Agency (Contract Number HDTRA-1-13-1-0031). 

Students Addressing Global Health Challenges: Lessons Learned

Maria Oden, Ph.D., Department of Bioengineering, Rice University
September 25, 2014 6 pm (Food starting at 5:30 pm)
Blum Hall B100

Through 8 years of experience with the Beyond Traditional Borders program at Rice University, we have developed, evaluated and, in some cases, implemented medical technologies in 16 countries around the world. This talk will focus on the lessons learned as we have become more successful at taking technologies from the undergraduate and graduate labs to implementation and, in some cases, to commercial distribution. Examples such as a bubble CPAP system, dosing clip, hemoglobinometer, phototherapy system and others will be highlighted.

Integration of paper microfluidic methods for detection of infectious diseases in low resource settings

Paul Yager, Ph.D., Professor, Department of Bioengineering, University of Washington
May 1, 2014 6 pm (Food starting at 5:30 pm)
Blum Hall B100

Major improvements in human health in the developing world (and significant reductions in the cost of healthcare in the developed world) could be achieved if we could decentralize the testing of pathogens from human samples, and do so at very low cost. One enabling technology that we have been exploring for 5 years is the use of porous matrices as a replacement for pumps in microfluidics. Under support of NIH NIAID, our lab leads a team developing a low-cost method for high-sensitivity protein-binding assays for point-of-care detection of infectious disease (initial target: influenza). The team consists of UW, Seattle Children’s Hospital, PATH, and GE Global Research. Under support of DARPA DSO, we are developing a multiplexable autonomous disposable nucleic acid amplification test system for the same purpose (initial targets Staphylococcus aureus and influenza). The team is the same, plus Gaetano Borriello, Ferric Fang, and Epoch Biosciences. Both systems are based on novel uses of inexpensive paper and paper-like membranes. Both are designed to be instrument-free fully-disposable diagnostic platforms capable of sensitive detection of multiple pathogens from biological samples. The designs allow sample-to-result testing anywhere, and will be simple enough for untrained users. Output will be an image capable of being captured (and transmitted for interpretation) by a smart phone, which would be an optional instrument to help analyze test results. 

Both prototypes are designed to detect pathogens from a nasal swab, and share the use of a number of novel paper-fluidic tools. Recent progress on the protein binding assay includes development of de-novo proteins for viral protein capture by the David Baker laboratory, methods for analyzing their association in paper, and their controlled release from the substrates. In the nucleic acid assay, we have demonstrated the detection of a few Staphylococcus aureus bacteria using an isothermal amplification of characteristic bacterial DNA sequences. The prototype integrates 1) lysis of the nasal swab sample in a tube, 2) isothermal amplification of the DNA obtained, and 3) detection of the amplified target using colored labels on a lateral flow strip. 

Point-of-Care Testing in At-Risk Patient Populations: Experiences from a Regional Burn Center

Nam Tran, MD, UC Davis
April 17, 2014 6 pm (Meet and greet with food at 5:30 pm)
Blum Hall B100

    Burn injury results in profound alterations to homeostasis. For instance, significant fluid loss occurs immediately following burn injury as the result of systemic inflammation and evaporative water loss. This so-called “burn shock” phase requires massive fluid resuscitation to maintain adequate blood pressure and tissue perfusion.  Infections are also common in burn patients. Studies have observed up 97% of patients with >20% total body surface area burns experiencing sepsis over the course of their hospital stay, and about 75% of burn-related deaths being associated with wound infections.
    Early recognition of inadequate burn shock resuscitation and sepsis are instrumental to patient survival. Unfortunately central laboratory-based tests are not suitable for rapid-response testing during burn critical care. To this end, burn patients stand to benefit from point-of-care testing (POCT). Defined as “medical testing at or near the site of patient care”, POCT improves patient outcomes by reducing the therapeutic turnaround time (i.e., time from test order to treatment) and facilitating evidence-based practices. Innovative biomarkers of organ dysfunction and molecular pathogen detection methods, when used at the point of care, could accelerate clinical decision-making and improve outcomes in high-risk critically ill burn patients.  

Information in your fingertips, at your fingertips

Octavian Florescu, PhD, President at Silicon BioDevices
April 3, 2014 6 pm (Meet and greet with food at 5:30 pm)
Blum Hall B100

The human body consists of approximately 100 trillion cells all communicating with each other by tranmittting various analytes. Silicon BioDevices has developed the next generation point-of-care testing (POCT) technology: a small disposable device with integrated display that measures multiple analytes directly from a finger stick of blood and instantly transfers the results to a mobile device or wireless server accessed electronic medical record (EMR) system. This breakthrough innovation will help integrate in vitro diagnostic test information into patient care workflow and allow many more blood tests to be performed in non-medical settings. This disruptive approach raises the bar on body fluid testing at the point of specimen collection by delivering performance equal to the clinical laboratory. This technology will put the information in your fingertips, at your fingertips.

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Dr. Octavian Florescu, PhD, is the inventor of the CMOS biosensor technology at the core of the Silicon BioDevices platform. He has over 10 years of experience in the semiconductor/IT space working with DEC, GE, Nokia, Quake Technologies and Qualcomm, where he developed control systems for nuclear reactors, software for network management, high speed digital blocks for 10Gb/s and 40Gb/s Ethernet, baseband PLLs for digital timing and RF front-ends for cellular communication. He received his B.S. in Computer Engineering from the University of Waterloo, Canada in 2004, and his PhD in Electrical Engineering from UC Berkeley (Boser lab), with a minor in Molecular and Cell Biology in 2010. Outside of IC design and biotechnology research, his interests include economics, surfing and downhill skiing.

Biomarker tests for tuberculosis: Point-of-residence diagnostics
Lee W. Riley, MD, School of Public Health, UC Berkeley
March 13, 2014 6 pm (Meet and greet with food at 5:30 pm)
Blum Hall B100

Globally, tuberculosis (TB) is the most common cause of adult death due to an infectious disease. The diagnosis of TB is complicated. Simply diagnosing the disease will not contribute to the control of this problem. TB control requires application of diagnostic tests at multiple levels. Most importantly, TB diagnostic tests need to be designed to facilitate transmission interruption. This is because by the time an individual with TB reaches a point-of-care (POC) facility, such a person would have infected at least 10 other close contacts. From these close contacts, new cases of TB will arise and such cases will infect 10 others before the diagnosis can be made. Thus, TB diagnostics must include the following performance characteristics: 1) predict who among those with latent TB infection (LTBI) will progress to active disease, 2) monitor response to treatment, once the treatment is initiated; 3) predict relapse TB; and 4) differentiate drug-resistant from drug-susceptible TB. We are analyzing host biomarkers that have these performance characteristics. In particular, we are examining host responses to Mycobacterium tuberculosis phospholipid molecules predictive of these stages of TB infection. Once these biomarkers are identified, we plan to adapt an immunochromatographic platform to use the tests at the places where people live. In this way, we will be able to target high-risk populations with chemotherapy and greatly reduce the chances of new transmissions.

Childhood pneumonia: identifying shortcomings and developing solutions for low-resource settings
Anoop Muniyappa, UC Berkeley-UCSF Joint Medical Program
February 27, 2014 6 pm (Meet and greet with food at 5:30 pm)
Blum Hall B100

Pneumonia is the leading cause of mortality in children under five worldwide, accounting for over 1.3 million deaths annually. The greatest burden of disease is seen in developing countries, where pneumonia disproportionately affects children in the poorest segments of the population. While a number of risk factors such as poor hygiene, nutrition, and environmental conditions significantly increase a child’s risk for developing pneumonia, the high rates of mortality result from a lack of adequate treatment in resource-poor settings. Our discussion will focus on current standards of care and the shortcomings in terms of care-seeking, diagnostics, and treatment in these areas.

Microarrays and unbiased next-generation sequencing — moving towards clinically actionable diagnostic assays for pathogens
Charles Chiu, Assistant Professor UCSF School of Medicine
February 13, 2014 6 pm (Meet and greet with food at 5:30 pm)
Blum Hall B100

Microarrays and unbiased next-generation sequencing (NGS) technology enables the detection of novel or uncommon pathogens directly from clinical samples, but its routine implementation in clinical and public health settings has been hindered by issues of cost, turnaround time, and bioinformatics analysis of complex datasets. Here we will describe the use of the technology in the clinical laboratory to validate novel, ultra-sensitive assays that have the potential to transform infectious diseases. This talk will focus on the development and validationof a broad-based microarray assay for the detection of tickborne pathogens (TickChip), and on the implementation of an unbiased NGS approach for diagnosis of infectious diseases. In particular, actionable diagnoses were obtained using NGS for recent cases of fulminant meningoencephalitis in two critically ill patients.

D-Rev: A non-profit that acts like a for profit to deliver world-class medical devices in underserved markets
Samuel Hamner, Ph.D., Design Engineer at D-Rev
Blum Hall B100
5:30PM dinner, 6:00PM seminar

D-Rev is a nonprofit product company that designs, and works with local partners, to deliver products that improve the lives and increase the incomes of people living on less than $4 per day. We are focused on developing products that alleviate poverty by delivering world-class, user-centric devices to base-of-the pyramid users who are often overlooked because of immature markets, complicated entrance strategies, and unique distribution challenges.

D-Rev follows three core principles in developing and delivering products: (1) Our products are world-class, meaning they perform on par or better than the best products on the market. (2) We take a market-driven approach, meaning that our business models are designed with profit margins built in to integrate into local markets and sell through the private sector. (3) We take a user-centric approach, working closely with end-users, field experts, key opinion leaders and all stakeholders in the customer value chain.

In this talk, I’ll give an overview of D-Rev, and then briefly discuss our two main products: Brilliance, a phototherapy device to treat neonatal jaundice, and the ReMotion Knee, a low-cost prosthetic knee for above-knee amputees.

YOU MAY REGISTER FOR THE DIAGNOSTICS BY DESIGN WORKSHOP HERE!

The Diagnostics by Design workshop is an interdisciplinary forum for discussing the challenges and lessons learned in developing and implementing global health technologies, specifically at the point of care. Through interactive talks, a panel discussion with experts from industry and academia, and a hands-on build session, we will explore the challenges associated with translating technologies beyond the lab. This workshop will draw on the expertise and experience of individuals from across disciplines to explore collaborative solutions to global health issues. The workshop will feature Columbia Professor and mChip inventor Samuel Sia as the keynote speaker. See our eventbrite page for registration. The tentative agenda for the day is shown below:

Agenda


8:30-9:30 Registration with breakfast
9:30-10:30 Session 1 – Kickoff with keynote by Sam Sia, Associate Professor, Columbia University
10:30-10:45 Coffee break
10:45-11:45 Session 2 – Jim Gallarda, Senior Program Officer, Diagnostics at Bill & Melinda Gates Foundation
11:45-1:00 Lunch
1:00-2:00 Session 3 – Amy Lockwood, UCSF Global Health Sciences
2:00-2:15 Coffee break
2:15-3:45 Session 4 – “The Value Chain for Diagnostics: Concept to Product to Impact” – Panel discussion with opening talk and moderation by Madhu Pai, Associate Professor, McGill University
        Panelists:
            Shashi Buluswar, Executive Director, LIGTT
            Eva Harris, Professor, UC Berkeley
            Daniel Fletcher, Professor, UC Berkeley
            Glenn Johns, Director of Global Health Diagnostics, Alere
            Daniel Laser, CEO, Wave80 Biosciences
            David Persing, Executive Vice President, Cepheid
3:45-4:00 Coffee break
4:00-5:30 Session 5 –  ”Build a Device” hosted by Tekla Labs
5:30-5:45 Closing remarks
5:45-6:45  Reception with drinks