BUSINESS NEWS
Testing times
Quicker diagnostic tests are needed for Covid-19 but
the challenges in making them are considerable
13 April 2020 / www.theengineer.co.uk
The message from the World
Health Organisation’s
director general could
not have been more
unequivocal when he
declared Covid-19 ‘the
defining global health crisis of our
time’.
On March 16, 2020 Dr Tedros
Adhanom Ghebreyesus said, “We
cannot stop this pandemic if we
don’t know who is infected. We
have a simple message for all
countries: test, test, test.”
Public Health England has
developed what it describes as
a highly sensitive test to detect
the virus, with results returned
in 24 hours. The need for more
tests that produce quicker results
is, however, a matter of global
urgency to halt the inexorable
spread of the virus.
One company on the front line
of this UK effort is Bedfordshirebased
rapid diagnostic specialist
Mologic, which has been
warded around £1m from a £46m
governemnt fund set up to help
efforts aimed at controlling
Covid-19.
On announcing the award,
Mologic’s medical director, Dr
Joe Fitchett, said rapid detection
of the virus is important to stop
its spread and to this end the
company will develop a point-ofneed
diagnostic test device.
The complexity of the task
cannot be underestimated. Dan
Haworth, head of diagnostics
and partner at Cambridge
Design Partnership, told The
Engineer that diagnostic device
developers typically design
point-of-care systems that consist
of a consumable part, and a
reusable reader that controls
the test process, provides the
user interface, stores the results
and connects to hospital/lab
networks to provide real time
epidemiological monitoring.
“The consumable needs to
carry out complex processing
of the sample and reagents. For
example, sample introduction,
sample preparation, nucleic acid
amplification and detection,” he
said. “The amplification process
generates billions of copies
of ‘amplicon’ amplified DNA
strands so the whole process
must be sealed, otherwise leakage
could cause false positives for a
prolonged period of time.”
Dominic Lloyd-Lucas, head
of engineering technology
at 42 Technology, a product
development and engineering
consultancy, explained that
the Covid-19 virus comprises a
protein and the genome sequence
is known from data released by
Chinese scientists.
“The key in developing a
rapid, handheld diagnostic device
is being able to detect small
quantities in samples of saliva
or sweat as the assay needs to be
both sensitive and specific to this
target,” he said. “PCR polymerase
chain reaction is slow as the
amplification stage takes time, and
although direct detection offers
a potential shortcut there will be
issues in getting a representative
sample into the device: biosamples
can be hugely variable and
with small samples the risk of
contamination or another artefact
may be higher.”
Indeed, sample preparation is
a complex process that includes
breaking open the virus to
extract the RNA (ribonucleic
acid), washing away inhibitors,
concentrating the RNA and mixing
it with freeze dried reagents to
initiate amplification. According to
Haworth, key technical challenges
involve implementing these
complex functions in an easy-to-
IF THE ASSAY IS TOO EASILY TRIGGERED THEN
HEALTHCARE WORKERS COULD BE OVERWHELMED WITH
THOSE WHO DO NOT NEED TREATMENT
use device.
“The reader system needs
to provide valving, timing and
actuation of fluids and reagents
to control the test process – but
making this reliable and low
cost is a challenge,” he said.
Also, special attention needs to
be given to ensure the device
architecture is suitable for high
volume manufacture, such as
multi-cavity injection moulding
and test performance is robust
to manufacturing and assembly
tolerances, he added.
“There are a lot of technical
risks and challenges to consider
when designing these systems,”
he said.
Diagnostic device developers
and drug makers are being aided
by regulatory bodies such as the
US Food and Drug Administration
(FDA), which is fast-tacking device
deployment under ‘emergency use’
conditions, a scenario applicable
to Roche which has been
authorised ‘emergency use’ to run
a Covid-19 test on Cobas 6800 and
8800 lab analysers.
“In a pandemic situation,
the regulators will be under
intense pressure to permit fast
development,” said Lloyd-Lucas.
“But this has to be balanced
against the possible negative
outcomes if the assay fails to
detect infection and gives the
all-clear wrongly, meaning that
an infected person goes back into
the community and unwittingly
infects others.
“Conversely, if the assay is too
easily triggered... then healthcare
providers could be overwhelmed
with disproportionate numbers of
those who do not need treatment.
Sufficient evidence of specificity
and sensitivity needs to be
demonstrated and the relevant
clinical scientist teams will have
to make a judgement of this,
and to persuade the regulators
accordingly.”
News analysis
WRITTEN BY JASON FORD
/www.theengineer.co.uk