Field-based patient trial for cell-free Zika testing delivers highly
accurate results

Date:
March 7, 2022
Source:
University of Toronto - Leslie Dan Faculty of Pharmacy
Summary:
Researchers have led one of the first field trials for a synthetic
biology-based diagnostic using patient samples. This work, conducted
on- site in Latin America, reveals the potential for cell-free
synthetic biology tools and companion hardware for providing rapid,
de-centralized, and low-cost patient testing for infectious diseases
like the Zika virus.



FULL STORY ==========================================================================
An international team of researchers, headed by experts from the
University of Toronto's Leslie Dan Faculty of Pharmacy, has led one of
the first field trials for a synthetic biology-based diagnostic using
patient samples. This work, conducted on-site in Latin America, reveals
the potential for cell-free synthetic biology tools and companion hardware
for providing rapid, de- centralized, and low-cost patient testing for infectious diseases like the Zika virus.


========================================================================== Study results, published today in Nature Biomedical Engineering,show
that the novel diagnostic platform has analytical specificity and
sensitivity equivalent to a US Centre for Disease Control PCR test for
Zika and a diagnostic accuracy of 98.5 per cent with 268 patient samples collected in Recife, Brazil. The platform is also programmable and can
be similarly applied to detect any pathogen sequence. In addition to
validating highly accurate diagnostic results for Zika, the team also
achieved similar diagnostic performance for chikungunya virus, another mosquito-borne arbovirus.

"We see emerging diagnostics, like the paper-based tests we've developed,
as having tremendous near-term potential to augment existing PCR capacity, improve equity in access to health care, and aid in the responses to
public health crises," said Keith Pardee, assistant professor in the
department of pharmaceutical sciences, Leslie Dan Faculty of Pharmacy, University of Toronto.

Prior to the current global COVID-19 pandemic, the 2015/2016 outbreak
of Zika virus in Latin America emphasized the urgent need for rapid and low-cost testing that can be deployed beyond the reach of centralized diagnostic labs, explains Pardee who has a Canada Research Chair in
Synthetic Biology and Human Health. "We were investigating and developing
this technology well before the COVID-19 pandemic brought these issues to
light at the global level. We've now been able to apply it and validate it
in a region of endemic disease, which is really promising because these
tools are meant to enable health systems to better respond to future
outbreaks of infectious disease, particularly in low- resource settings,"
he said.

The portable diagnostic platform is a combination of a cell-free,
paper-based test and a field-ready companion device that allows data
to be collected using image-based color analysis -- purple for positive
and yellow for negative.

Called "PLUM" (Portable, Low-cost, User-friendly, Multimode), the
toaster-size reader presents results from up to 384 samples and displays
them in a single image capture. The hardware and software that make up
PLUM were originally developed by co-authors Livia Guo and Seray C,ic,ek
as part of their graduate work in the Pardee lab. To keep production
costs low, Guo and C,ic,ek, co- founders of LSK Technologies, used
customizable software programs and off-the shelf electronics, enabling
PLUM to be built for approximately $500 USD per unit.

On the molecular side, the cell-free tests can be freeze-dried, allowing
for distribution without refrigeration and, significantly, all of the
molecular components of the test are independent of the PCR-supply
chain. "Here we have demonstrated that these two technologies combined
create a low-cost, highly accurate diagnostic tool," said study lead
author Margot Karlikow, a postdoctoral fellow in the Pardee lab from 2016
to 2021 and now co-founder of En Carta Diagnostics. "We also demonstrated
that it is feasible to transport the platform across a significant
distance and implement it effectively in another country. In many low-
and middle-income countries, there is no PCR testing available outside
of main cities, so the ultimate goal is that this platform be used as
a high-quality alternative to PCR in more regional settings," she said.

Dr. Lindomar Pena, department of virology, Oswaldo Cruz Foundation
(Fiocruz), led the Brazilian team that collaborated on the project. "This robust diagnostic platform displayed desirable features to be used in developing countries such as Brazil and in laboratories with basic infrastructure. We hope it can be further developed and deployed in
the Brazilian network of public health laboratories to diagnose Zika
patients, trace contacts and identify hot- spot areas with active
community transmission," he said.

Showing that the platform could be transported and accurately detect
Zika virus in patient samples is a significant step forward in creating
more accessible and de-centralized testing, says Pardee. However, the extraction of RNA from patient samples still requires liquid handling
by skilled technicians at this stage. "With performance on patient
samples now validated, we are tackling these next challenges, like sample preparation, so that the platform and PCR- like diagnostic capacity can
be distributed more broadly into the communities where they are needed." ========================================================================== Story Source: Materials provided by University_of_Toronto_-_Leslie_Dan_Faculty_of_Pharmacy.

Original written by Kate Richards. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Margot Karlikow, Severino Jefferson Ribeiro da Silva, Yuxiu Guo,
Seray
Cicek, Larissa Krokovsky, Paige Homme, Yilin Xiong, Talia Xu,
Maria- Angelica Caldero'n-Pela'ez, Sigrid Camacho-Ortega, Duo Ma,
Jurandy Ju'nior Ferraz de Magalha~es, Ba'rbara Nayane Rosa'rio
Fernandes Souza, Diego Guerra de Albuquerque Cabral, Katariina
Jaenes, Polina Sutyrina, Tom Ferrante, Andrea Denisse Benitez,
Victoria Nipaz, Patricio Ponce, Darius G. Rackus, James J. Collins,
Marcelo Paiva, Jaime E. Castellanos, Varsovia Cevallos, Alexander
A. Green, Consta^ncia Ayres, Lindomar Pena, Keith Pardee. Field
validation of the performance of paper-based tests for the detection
of the Zika and chikungunya viruses in serum samples.

Nature Biomedical Engineering, 2022; DOI: 10.1038/s41551-022-00850-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220307113007.htm

--- up 1 week, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)