MEAM-ESE SENIOR DESIGN PROJECT - ADVISOR SUBMISSION FORM
1. Project Title: “An Instrument for On-Site Detection of Pathogens in Food”
2. Proposer's Name: Haim Bau (MEAM), Changchun Liu (MEAM), Shelley Rankin (Vet School),
and Ken Laker (ESE)
E-mail: laker@seas.upenn.edu, bau@seas.upenn.edu, srankin@vet.upenn.edu,
lchangc@seas.upenn.edu
3. Brief Project Description:
Foodborne diseases are common in developed and developing countries and cause human suffering,
death, and significant economic cost in terms of healthcare, lost productivity, food destruction, halts in
production, and recalls. Annually, foodborne pathogens cause over 48 million illnesses in the US
alone. Foodborne diseases can be prevented and the associated damage minimized with appropriate
food testing along the spectrum from farm to fork.
Our objective is to design, develop, and validate a portable, inexpensive, diagnostic instrument for onsite, molecular detection of pathogens in various food matrices. The project is interdisciplinary and
flexible. Based on team members interests, the project may involve (i) the development of a
microfluidic system for sample preparation and isothermal enzymatic amplification of nucleic acids
associated with target pathogens and/or a suitable sensor information acquisition system that will
interface with a smart phone. The smart phone will be used for (in the order of priority) (i) fluorescent
signal detection (with the phone camera) and data analysis; (ii) instrument control; (iii) transmission of
test results to a central location; and (iv) the collection of pertinent information to assist health officials
in identifying the source of contamination.
Expertise unavailable to the team will be provided by the participating laboratories. The technology
developed in this project can also be applied to detect pathogens in body fluids such as blood, saliva,
and urine to diagnose various diseases and cancer markers.
Reference:
C. Liu, E. Geva, M. Mauk, X. Qiu, W. R. Abrams, D. Malamud, K. Curtis, S. M. Owen, and H. H. Bau,
2011, An Isothermal Amplification Reactor with an Integrated Isolation Membrane for Point-of-Care
Detection of Infectious Diseases, Analyst 2011, 136, 2069-2076.
C. Liu, M. G. Mauk, R. Hart, M. Bonizzoni, G. Yan, and H. H. Bau, 2012, A Low-Cost Microfluidic Chip
for Rapid Genotyping of Malaria-Transmitting Mosquitoes, PloS One 7 (8), e42222.
Liu, C., Mauk, M., Hart, R., Qiu, X., and Bau, H., H., 2011, Self Heating Cartridge for Molecular
Diagnostics, Lab on Chip 11, 2686-2692.
4. Project Design Objectives:
The project includes a few components. The scope of the project depends on the team’s size,
expertise, and interests. Below, we describe the two main components of the project. Variants are
also possible. The two main components of the project are:
(a) The microfluidic cassette with a processor and
(b) The smart phone interface
a.
The microfluidic cassette
This part of the project will be carried out by individuals with a background in Mechanical
Engineering. The basic chip design for the isolation and amplification of nucleic acids is depicted in Fig.
1. The chip is milled in acrylic and contains amplification reaction chambers equipped with flow
through membranes for the isolation and purification of nucleic acids. The various reaction chambers
can be used for multi-target detection, calibration, and discrimination between wild types and drugresistant bugs. Although functional, the chip is not yet fully automated. Opportunities are available to
further develop the chip to accommodate sample preparation, reagent storage, pumping, and
exothermic reaction-based self-heating (as an alternative to electrical heating) and to devise fabrication
techniques consistent with low cost, mass production.
The chip can operate either as instrumented with electrical heater or uninstrumented with the
exothermic reaction-based heater. If an electrical heater is selected, the team will need to develop a
processor to thermally control the chip’s temperature. If an exothermic reaction-based heater is
selected, the team will need to develop appropriate thermal
control scheme to isolate the chip temperature from varying
ambinet conditions.
Smart Phone – Based Interface
The presence and quantity of target molecules is
determined based on the amount of product (amplicon)
generated by the enzymatic amplification process. Our
detection method is based on monitoring fluorescent emission.
We are, however, willing to consider other detection modalities
such the monitoring of solution pH. Below, we focus on
fluorescent emission.
The emission intensity from the various reactors will be
monitored with the cell phone camera either continuously (in
real time) during the nucleic acid amplification process or after
certain predetermined time (end-point detection). In a senior
design project last year (Fig. 2), the team designed illumination
to provide uniform excitation to the amplification reactors and
filters to minimize the overlap between excitation and emission
spectra. The work was not completed. It is necessary to debug
the system, verify its performance, and complete the software
to process the data and report test results.
The data will be displayed, for example, in a graphical form
as emission intensities (obtained from various reactors) as
functions of time. The program will determine the threshold
times needed for the emission intensities to exceed a
predetermined value and provide estimates of the numbers of
target molecules in the sample
If the team selects to focus only on the smartphone
interface, we will provide the team with the chip shown in Fig.
1 and with assays to generate the fluorescent signals to be
detected.
b.
Fig. 1: A plastic chip containing three
reactors for the isolation, purification,
and amplification of nucleic acids
associated with target pathogens. The
chips are currently milled. There is a
need to develop fabrication methods
consistent with large quantity
production.
A prototype smartphone-based
5. Prior Experience:
detection, processing, and
Individuals interested in part (a) of the project would benefit
communications. H, M, N, stand,
from MEAM 575- Micro and Nanofluidics (Fall 2014) and
respectively, for high, medium, and low
CFU concentrations of target bugs.
MEAM410/510 - Design of Mechatronic Systems or
equivalent. Machine shop experience is a plus.
Individuals interested in part (b) of the project would benefit from experience in smartphone (.e.,
android) programming, interest in applications development, and some knowledge of optics.