Diagnosing malaria using magneto-optic sensors
Submitting InstitutionUniversity of Exeter
Unit of AssessmentGeneral Engineering
Summary Impact TypeTechnological
Research Subject Area(s)
Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Medical Microbiology
Summary of the impact
Malaria is endemic in more than 100 countries but its rapid and accurate
diagnosis in locations remote from clinical laboratory facilities remains
challenging yet desperately needed. This case study describes how
scientific discoveries made in the field of digital data storage have been
developed and applied to deliver a rapid, reliable and low cost malaria
diagnosis sensor suitable for field application. Diagnostic devices have
been both laboratory-tested and clinically trialled on over 900 patients
under adverse field conditions in malaria endemic countries with very
promising results. The health impact includes not only
significantly reducing unnecessary treatments but potentially saving
millions of lives.
For many years, Professor David Newman studied the magneto-optic
spectroscopy of materials to optimise their performance as digital data
storage media (1). This was based on the premise that the magnetic state
of a material produces changes in many of its physically measurable
parameters including its optical properties. After joining Exeter
Engineering in 2003, and now based in the Functional Materials Group,
Newman realised that this must also apply to organic molecules in
biological systems. So, in principle, any disease which modifies the
biochemistry of physiological systems dependent on iron should be
detectable through magneto-optic measurements.
The basis of the detection approach is exploitation of a magneto-optic
mechanism observable in liquids and gases called the Cotton-Mouton effect.
In most fluids this is very small, but interestingly many biological
fluids when subjected to an applied field generate a much larger effect,
the Extraordinary Cotton-Mouton Effect (ECME). So, if the pathology of a
particular disease modifies the biochemistry of a physiological system to
produce a change in the ECME of some testable fluidic component of the
system, for example blood, then the disease ought to be detectable through
It was decided to test this idea on the highly significant disease of
malaria. The pathological action of the infecting parasite is known to
produce substantial structural impact on the haemoglobin within red blood
cells. The toxic haem component of the blood is rendered harmless to the
parasite by its conversion to haemozoin in the form of rod shopped
nano-crystals. These structures were expected to generate a detectable
ECME signal that would correlate with disease progression.
The foundational research required to test this hypothesis was carried
out by a consortium of seven academic and industrial partners led by
Newman and funded by an EC 6th Framework grant [i]. Undertaken between
2005 and 2009, this involved developing new magneto-optic instrumentation
to handle liquid samples and establishing the sensitivity required to
detect and quantify the changes wrought by the malaria parasite on the
haemoglobin in red blood cells (2, 3). By artificially creating calibrated
samples typical of the blood taken from malaria patients it was determined
that the Cotton-Mouton effect is, under laboratory conditions, a rapid and
sensitive (≈5pgm/µl) volumetric assay for haemeozoin. Formal blind
laboratory studies using real patient blood samples collected in malarial
endemic regions were then carried out and confirmed the potential of the
technique (4). An even more exciting discovery was that the principle is
also realisable in non-invasive format (5) by accessing the blood supply
below the fingernail. This could significantly minimise cross infection
risks to health-workers although significant challenges remain in
To ensure maximum impact, reliability and effectiveness a series of
clinical field trials was conducted in the most adverse environments. This
was needed since the sensitivity of the diagnosis depends on the amount of
haemozoin present in a patient's blood, which in turn is related to the
different stages of the parasites life cycle as indicated by blood
parasite count. These are described in section 4.
References to the research
1. Carey R, Newman DM & Thomas BWJ. (1995) Magneto-Optic Recording, Journal
of Physics D: Applied Physics, 28, 2207-2227. **
2. Newman DM, Heptinstall J, Matelon RJ, Savage L, Wears ML, Beddow J,
Cox M, Schallig HD, Mens PF. (2008) A
magneto-optic route toward the in vivo diagnosis of malaria:
preliminary results and preclinical trial data, Biophysics
Journal, 95,. 2, 994-1000. **
** Papers that best indicate quality of underpinning research.
i. Newman, D. (PI) Novel magneto-optical sensors for malaria
diagnosis, EC 6th Framework Programme. Priority: IST-NMP-2
Bio-Sensors for Diagnosis and Healthcare, FP6-016494, €1,450,000,
ii. Newman, D. (PI) Novel magneto-optical biosensors for malaria
diagnosis. Bill & Melinda Gates Foundation Grand Challenges
Explorations Initiative, Grant Number 53086, $100,000, 2009-2010.
iii. Newman, D. (PI) Novel magneto-optical biosensors for malaria
diagnosis. Bill & Melinda Gates Foundation Grand Challenges
Explorations Initiative, Global Health Grant Number OPP1024428, $996,171,
2011 - present.
Details of the impact
Malaria diagnosis is challenging and is currently either carried out
symptomatically or by the use of antigen detecting rapid diagnostic test
(RDT) sticks. However, studies by the World Health Organisation [a] found
detection rates reduced to less than 75% for more than half the RDT
devices tested with some products returning values as low as 25%.
Consequently in many regions where malaria is endemic there is a tendency
to treat patients automatically (and particularly children under five)
presenting with fever for malaria. Often this is incorrect and such
over-prescribing is one of the major factors driving development of drug
resistance in the malarial parasite.
The laboratory trials had proven to be highly successful and promising to
the point that the global medical industry recognised the fledgling device
as one of the top ten medical devices of 2010 [b]. The clinical
field trials were therefore important to confirm this promise and were
focused particularly on the issue of over-prescribing, but also on
accurate and timely diagnosis. In addition, the device needed to be
impervious to environmental effects and able to return a reliable
diagnosis in less than two minutes under the most adverse field conditions
irrespective of the operator.
Field trials were held in Kenya in 2008 [c] based on 682 patients
showing clinical signs of uncomplicated malaria. The original prototype
instrument was evaluated under blind clinical conditions against expert
microscopy. It returned initial sensitivity and specificity values of 85%
and 64.5% respectively although it was noted that several cases of high
level infection (parasitaemia) were missed. This prototype was the size of
a small filing cabinet but its performance was promising enough [d, e] to
secure prestigious funding from the Bill and Melinda Gates Foundation
(ii, iii) for its miniaturisation and continued development.
A radical redesign realised the diagnostic platform in a portable
hand-held format about the size and weight of a credit card reader.
Several such devices have subsequently been manufactured in-house at
Exeter. It is estimated that each device could be mass produced for less
than $200 with tests costing 25 cents each, much lower than current RDTs.
Devices in this format were field trialled over the summer months of 2012
in collaboration with Prof. Francois Nosten and Dr Stephane Proux at the
Shokolo Malaria Research Unit (SMRU) in Thailand [6, f]. This was a study
of a population of 155 patients composed primarily of migrants from across
the Burmese border and yielded what at first seemed disappointing results;
sensitivity 41% to 56% — specificity 96% to 100%. However the false
positive count was essentially zero, indicating the haemozoin
concentration in these samples was at or below the device detection limit.
This finding was reinforced by expert diagnostic microscopy that reported
that infection was at the very early stages in all samples tested. Thus
these suppressed results are likely a consequence of the atypical study
population but nevertheless they do indicate it is essential to further
boost instrument sensitivity at the bottom end of its range to pick up
very early infection. This is possible as design of the portable devices
was based on the data obtained in Kenya. Despite this, results clearly
indicate that these instruments are the most sensitive of all means of
detecting haemozoin in blood and that they will function under conditions
where microscopy is completely impractical and RDT's environmentally
The technique as patented [g] compared very favourably with other
existing and developing diagnostic technologies in UNITAID's 2011
review [h] of the malaria diagnostic landscape for the World Health
Organisation. When commercialised and following further development, the
sensor is well placed to reach the Global Health Diagnostic Forum's goal
[i] for malaria diagnosis. This is to substantially reduce the more than
400 million unnecessary treatments administered each year but also to save
upwards of 1.8 million adjusted lives per year.
Finally and significantly,
it has become clear that the technology is immediately applicable to the
diagnosis or other classes of disease and also realisable as a generic
multi-spectrum point-of-care device. It is potentially able to sensitively
diagnose any disease or condition for which a biomarker and biomarker
receptor have been identified and even diagnose several diseases
simultaneously from a single fluid sample. Both these advances have been
protected by patent applications filed in 2011 [j].
Sources to corroborate the impact
a. Malaria Rapid Diagnostic Test Performance: Results of WHO product
testing of malaria RDTs: Round 1 (2008): ISBN 978 92 4 159807 1. PDF
b. Report by the Medical Device Developments editor lists our
magnetic-optical device as one of ten technologies that have caused the
most excitement in 2010 in terms of how they will alter patient care in
the years ahead. http://www.medicaldevice-network.com/features/feature106579/
c. Netherlands Trial Register (2008). Clinical evaluation of a
magnetic device for the diagnosis of malaria. NTR Number NTR1532:
d. Press announcement of Gates Foundation award (2011) http://www.bbc.co.uk/news/uk-england-devon-1413854
e. Lead, Discovery & Translational Sciences team, Bill and Melinda
Gates Foundation, 440 5th Ave N., Seattle, WA 98109, USA.
f. The trial was registered and the protocol approved under the Oxford
Tropical Research Ethics Committee (Oxford University). Reference: 22-12.
PDF approval letter supplied
Newman DM. Hemtinstall, J. Devices and Methods for Detecting
03b2-haematin and haemozoin. This is the primary patent protecting
the diagnosis of malaria by magneto-optics. International Patent
Application Number PCT/GB2007/004300 filed 10/ 11/2006. US Patent granted
3/07/2012 No 8,214,006. Currently undergoing examination in the EU, China
and India. http://www.google.com/patents/WO2008056171A2
h. UNITAID (2011). Malaria Diagnostic Technology Landscape, see
pages 55-59 and appendix pages 85 and 86, UNITAID Secretariat, World
Health Organisation, Ave Appia 20, CH-1211 Geneva 27, Switzerland. http://www.unitaid.eu/en/marketdynamics/malaria-diagnostics-landscape
i. Urdea M, Penny LA, Olmsted SS, Giovanni MY, Kaspar P, Shepherd A,
Wilson P, Dahl CA, Buchsbaum S, Moeller G & Hay Burgess, DC. (2006).
Requirements for high impact diagnostics in the developing world,
Nature, 73-79 doi:10.1038/nature05448.
Newman DM. Detection of Neurodegenerative Disease. This
patent protects the extension of the primary patent to the diagnosis of a
raft of neurodegenerative diseases. UK Patent Application Filed
26/08/2011, Number 1114733.7. PDF supplied.
Newman DM. Method and Device for Detecting an Analyte. This
patent protects the IP associated with a whole class of techniques with
the potential to enhance magneto-optic detection and signalling to allow
the development of multi-spectrum volumetric assay in a point-of-care
diagnostic device. UK Patent Application Filed 01/09/2011, Number
1115120.6. PDF supplied.