We want to create new standards
for medical diagnosis by becoming major actors in the field of
health/medicine in order to bring down the empirical antibiotic
treatment era.
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Our work
The birth of DIANE was possible thanks to a motivated, close-knit and dynamic team of 10 hardworking students from different fields of study (i.e law (Paris Sud), biology (Sup ‘Biotech), chemistry (Chimie ParisTech, ENS Cachan), and physics (ESPCI)).
Our main asset was the diversity of knowledge distributed amongst the team members: but we’re only students, and as such, we lack expertise. Thus, we have involved experts from diverse fields to help us build our project : Ms. Sylvie Renard Dubois, Dr Marcel Hollenstein, Dr Lebeaux, Dr Clauteaux, Ms. Couture and others, in order to learn from their experience, test ideas and listen carefully to their advices. Our project relies on a strong bond between all the members of our team, and on mutual support. We have organized our working time by making sure we could all fully understand every aspect of the project, by reporting back to others during bi-weekly meetings. Those meetings helped us develop autonomous behaviors and increased efficiency in our work, by including the opinions of others on all the subjects.
Moreover, we have worked with short iterations, and by creating numerous milestones along the way. This working method, inspired by Agile methodology (lean start up method) helped us minimize the risk of failure by involving as much users, customers and experts in our domain, to help us find solutions and answers to hypotheses we claimed, and ensure that we can get maximum reactivity on any oncoming problem. We kept in touch with reality by making little steps forward every day. We wanted to make sure that we would create a product that would stand up to the expectations of our market. In order to enforce this method in our team, at the end of each development phase, we have reviewed our strengths and weaknesses and made sure that we would get better at each new phase. This working mindset has helped us consolidate our project, by compensating our flaws with new solutions.
Context
Sepsis is a major cause of death in the world, which
consists in a widespread infection of the circulatory system or the
severe infection of an organ. Today, sepsis affects more than 30
million people each year in the world. It causes 1 death every 5
seconds, which means that by the time you’ve read this section of
our wiki, sepsis has already claimed the life of ... people.
In order to treat sepsis, doctors widely use large
spectrum antibiotics, which aren’t specific; they are effective but
also costly and are our last weapon against the strongest bacteria.
The use of reserve antibiotics comes from the lack of effective
diagnosis in order to identify the strain and the resistances of the
bacteria causing the sepsis. Furthermore, actual methods require
more than 24 hours of analysis before yielding results or require
specialists in order to use cutting-edge technologies like mass
spectrometry or PCR. Therefore, it is crucial that we develop new
rapid diagnosis methods to help doctors adapt the antibiotic
treatment to the strain and the resistances of the bacteria, thus
preserving our reserve antibiotics, while waiting for new treatments
like gene or phage therapies.
The consumption of antibiotics has gotten out of
control, leading to the rise of new resistances and putting at risk
the sustainability of our treatments, as well as prolonging hospital
stays due to the lack of efficient diagnosis or adapted treatment.
Furthermore, with the recent progress of antibiotic resistance and
the appearance of multi resistant bacteria, those treatments are
becoming less effective for sepsis. Each year, more than 700 000
people die from resistant bacteria, and this number is not going to
drop down any time soon: in 2050, more than 10 million deaths will
be caused by this disease.
Our Solution
We have elaborated a new rapid diagnosis method, based
on previous work, used to precisely identify the strain causing an
infection as well as following the status of the infection by
measuring the concentration of bacteria in any biological sample.
This will allow for determination of the efficiency of the treatment
given to the patient, and adapt it to the situation if need be.
Our method relies on the electrochemical detection of
bacteria, using carbon nanotube electrodes functionalized with
aptamers. Aptamers are single-strand DNA or RNA sequences which
identify specific targets through binding properties. In presence of
bacteria, aptamers will change their conformational structure, thus
modifying the close environment of the electrode and enabling us to
detect a potential difference. This signal is linear with the
logarithm of the concentration of bacteria; this equilibrium between
the two conformational structures of the aptamers only takes a
minute to establish. We have integrated this technology in a new
portable diagnosis device, usable in both laboratories by
researchers, doctors or practitioners; or even in harsh environments
like in a humanitarian context.
A refined design and advanced features allow for a very
simple use by any caregiver or doctor, without any expertise in
synthetic biology. For example, an automated measurement and washing
system will allow the physician to focus on the patient after
inserting the biological sample into the machine. In only a few
minutes, the result will be available and the doctor will be able to
make an effective diagnosis and treat the patient with the
appropriate antibiotic for the detected strain.
DIANE has the
ambition to become a great weapon against bacterial infections by
establishing the next generation of rapid diagnosis device for the
detection of infection-inducing pathogens, in both bedside medicine
and humanitarian context.
Our Business
DIANE has the ambition to
become the next generation of rapid diagnosis device for the
detection of infection-inducing pathogens in both bedside medicine
and humanitarian context.
Key partners
Key partners
A major part of our project was the designing step of our
product. To do so, we have worked with customers and partners
in this major step. We’ve been building long lasting
partnerships with doctors, (Ministère de la santé) and
researchers to make sure that our product could stand up to
their expectations. Co-designing the product with our
customers has helped us tailor its properties and how it
functions in order to solve all of the problems our customers
encounter daily. It also helped us establish a list of all the
materials we would need to use in our device for it to follow
the regulation about medical devices.
For example, today’s time consuming methods of bacterial
diagnosis is detrimental to the rapid treatment of bacterial
infections. Thus, designing a real fast diagnosis device will
considerably help doctors for the administration of the right
treatment to the patient.
The lack of portability for a lot of diagnosis devices is also
detrimental to the accessibility to those methods in a
humanitarian context. Thanks to Dr Pedro Clauteaux, we have
designed our device based on his advices and his experience
from his field work in South America (Amazon rainforest for
example). His interview taught us that doctors in such context
usually only bring the bare minimum for on place diagnosis,
including a centrifuge, a microscope... In such context, we
knew that we had to make our device as small as possible, and
to make the sample processing as simple as possible. Thus, our
work with SMC has made the automation step possible with the
use of their engineered pumps and valves for
milli/microfluidics systems.
Working with Dr Lebeaux has brought us a lot of knowledge
about the needs of hospitals concerning diagnostics :
distinguishing bacteria, from viruses or parasites is the
first step necessary today. Moreover, determining the strain
of the bacteria is a real added value for the treatment of the
patient, even more when a follow-up analysis is possible in
order to check the efficiency of the treatment, and thus
Furthermore, he also told us that clinical trials could be
done on non medical subjects in the first time in order to
test the viability of our device, and then prove that it could
be used in medicine and in human health diagnostics.
For the future, we will continue the partnership with SMC to
produce the parts necessary for our product, including parts
related to the micro-fluidic system. As for the beginnings of
our business, we will assemble the devices ourselves, but we
might consider using SMC’s expertise in assembly to outsource
this aspect of our work. Furthermore, as SMC is already our
main supplier in terms of electrical devices, we might
establish a preferential contract with them. Furthermore,
working with diverse research laboratories will allow us to
expand our aptamer database more rapidly, and thus provide
real solutions for our customers as soon as new discoveries
are made in this field.
Key activities
Key activities
Research
One of the main activities of our business will be research,
with a dedicated scientific team whose goal will be to
develop new aptamers for diverse bacteria strains, either
for already known bacteria that have mutated, or for new
strains that have not yet been studied. This will enable us
to detect a wider variety of strains, in particular for the
strains with new antibiotic-fighting mechanisms. This
activity will make it possible for us to deliver a
cutting-edge technology adapted to the evolution of our
environment, in a refined and easy-to-use product.
Maintenance
DIANE’s ergonomy will facilitate the use of our device, in
particular for the case of the replacement of the
electrodes. By selling a wide variety of electrodes, we make
sure that DIANE is able to detect an impressive amount of
pathogens. Thus, we propose to caretakers and doctors a real
maintenance of their purchase with a follow-up of the
development of new electrodes as they are created by our
research team. Moreover, those electrodes can last up to a
few months, thereby requiring regular replacement, even more
so in the context of repetitive use of our device in
hospitals.
Assembly
and Distribution
Another key activity will be the assembly of our device. We
will create custom devices for each client, with a specific
set of electrodes that our customers can decide upon. The
main parts of our device will be manufactured by different
furnishers and then delivered to our base of operation,
waiting to be assembled for each order. Our main key
activity linked to the assembly is still the sales and
distribution aspect of our device : DIANE. When the number
of sales is significant enough, we will subcontract this
assembly task. It will be introduced as a leading technology
in the new era of rapid diagnosis devices.
Key ressources
Key resources
Intellectual property
In the context of this project it’s important not to
minimize the legal aspect. A patent is a protective tool of
an invention and provides a temporary monopoly of
exploitation, thus constituting an exception to the
operating rules of the liberal economy. In France, article
L. 611-10 of the Intellectual Property Code comes back on
the European Patentability conditions and states that "new
inventions involving an inventive step and capable of
industrial application" are patentable. Before starting the
development of the DIANE project, we first checked the
existing patents and then ensured that the protectable
elements of our product were kept secret. We evaluate the
possibility of filing a patent by analysing precisely the
inventive step, i.e. for a skilled person, the invention
does not clearly result from the state of the art. In these
processes, we are supported by the Patents and Inventions
Department of the Institut Pasteur. Beyond protection on
French territory, we are considering protection on a
European scale with filing a patent to the EPO.
Human resources
Our human resources will be composed of experts in the
domain of biochemistry, biodetection, and aptamers. They
will develop new aptamers in order to respond to new needs.
Our business cannot exist without its research activity.
Aptamers are in constant development, but we need to develop
our own sequences thanks to our dedicated scientific team.
Value propositions
Value
proposition
Specificity
Our new diagnostic method enables faster patient care with a
diagnosis time reduced to only a few minutes; leading to the
administration of suitable antibiotics, in a context where
empirical large spectrum antibiotic therapies jeopardizes our
reserve treatments, as presented in the new AWaRe campaign
released by the WHO (click here to learn more). The bacteria
we are focusing on are : S. aureus, E. coli, S. pneumoniae, E.
faecium, S. enterica, P. aeruginosa and A. baumanii. This list
is composed of the bacteria put in the watchlist of the WHO in
this report.
Cost
efficient
Moreover, we will reduce the economic impact of bacterial
infections by fostering the use of more available antibiotics
because more specific of the strain detected. Today, a bad
treatment leads to a prolonged stay in hospital, additional
costs in diagnostics and patient handling, in working hours
for hospital staff… Enhancing diagnostic time will thus reduce
considerably the time of stay for every infected patient with
the help of an adapted early-on treatment.
Portability
and ergonomy
The simplicity of use of our diagnosis device is a real
added-value for our users. Beyond the rapidity of our method,
it also distinguishes from competitors with its portability.
Its total volume will not exceed 9 liters (20x15x30cm3) We
have decided to focus on a miniaturisation and automation
strategy for our analysis system to let doctors focus on the
real problem : the health of their patient. Once the sample is
inserted in the device, a pump will take mechanically push the
system and make sure the sample can reach the electrodes, and
then automatically wash the analysis system. All waste is then
collected in a cartridge for easier waste treatment. We also
give access to an easy to implement bacterial diagnosis in
developing countries, by bringing a new, simple, portable and
efficient method on the market. We give NGOs the opportunity
to bring diagnostics to remote populations in hard-to-reach
areas.
Customer relationships
Customer
relationships
We want to stay close to our customers in order to best meet
his needs. That is why the existence of a relationship of
trust based on interaction is essential for us. Indeed, as
part of our research and development activity, we will be
able to meet the requests of our various customers who wish
to have new aptamers adapted to new strains that we will be
fixed on electrodes. This will allow us to increase our
catalog by doing a medical surveillance. We will provide
training in the use of the device both to hospitals and to
personnel working in humanitarian areas. In addition, in the
event of technical problems with the device, we will take
into account customer complaints and we can lend a device
for the duration of the maintenance or replacement of the
device.
Channels
Channels
To start off, we wish to work with a restricted number of
customers and partners to obtain the first results with our
device. We want to get all their feedback to help us design
our device in a better way, and answer the needs of the
targeted market.
Afterwards, selling our device through medical catalogs will
enable us to reach towards more customers, mainly in
hospitals. The price of our device will allow health
providers to buy several devices to accomodate the need for
fast and rapid processing of samples in a hospital
laboratory, and enable them to begin saving money on extra
charges due to antibiotic resistance.
Finally, for both nursing homes (EHPAD) and humanitarian
organizations, we have investigated on direct sales through
a technical-sales engineer. We have also investigated the
possibility of selling our device as a service: we would
lend our device to such organizations, and then make a trade
for each diagnosis analyzed with our device. This method
makes our device more affordable for organizations that have
few resources and for which our device could be crucial.
In order to promote our products, we would like to go
further than selling our device to hospitals and
organizations around us. We would launch a communication
campaign around our device and will participate in several
professional conferences to create attractiveness around
DIANE. We will focus this campaign on the results and the
feedback we get from our Key Opinion Leaders, and from
famous experts on the subject, like Marcel Hollenstein from
the Institut Pasteur in the domain of aptamers, in order to
promote our device and its potential in bedside medicine.
We would like to keep a close-knit relationship with all our
customers, in order to give them the best service possible.
This relationship is the key to a sustainable business, to
develop our future products with the help of our customers,
and give solutions to their needs. This will be done through
recurrent communication with customers, and easily
accessible maintenance for all the devices out on the
market.
Customer segments
Customer
segments
For our business, we have found that we have a three way
segmented market: hospitals, NGOs and nursing homes.
Hospitals
Our first customer segment is represented by hospitals that
use bacterial diagnosis as a recurrent method. The main
challenge hospitals are going to face in the near future is
the need to reduce the costs and times of patient stays due to
infectious diseases. Our device is a real asset for our
customers to facilitate patient care as well as the speed of
diagnosis. Hospitals are prone to large expenses towards
patient care, with an average of 1200$ per hospital stay due
to resistant bacterial infection. In this context, our device
could facilitate the financial management of those structures
by bringing new diagnostics solutions to reduce the risk of
treatment failure. Furthermore, the detection of bacteria
nowadays requires 4 blood cultures that each cost up to 21
euros in France, whereas our device could bring down the
detection of pathogens down to … euros per analysis.
Humanitarian
organization
The second customer segment corresponds to NGOs working in
conditions where it isn’t always possible to get access to
laboratory equipment and analysis. Our device brings a simple
solution for those organisations with a portable and resistant
product, using a cutting-edge technology and a deeply thought
choice of materials. We have worked around a very specific
channel in order to bring our device to NGOs with very little
budgets, with a location system described more precisely in
the channels part of the canvas. (lien hypertexte)
Nursing homes
The interview with Ms. Sylvie Renard Dubois, member of the
DGOS and doctor in the infectious diseases of the Bejin
hospital, has brought to our attention that nursing homes are
another customer segment quite different from the other two.
The main problem of nursing homes is the fact that each
patient comes with their own personal primary care physician.
Facilitating the sampling and analysis of biological samples
in such homes will reduce the risk of severe infections. A
major concern remains the staining of the sample due to
bacteria found on the skin or in the environment of the
patient, which needs a thorough clean handled by the
caretaker.
Analysis
laboratory
The last customer segment that doesn’t take part in our
three-way segmented market are private laboratories. We have
interviewed a doctor from such structure in order to assess
the needs and expectations of this potential customer for our
device. Thanks to the answers of Dr. … we have concluded that
our device will not be useful for this context. Today,
analysis time is not a real problem for laboratories, in fact,
administration tasks require more time to perform than the
analysis itself; thus providing more rapid diagnosis won’t
help doctors in their work, as the results can’t be given to
the patients (often suffering from light infections from the
urinary tract or in a blood sample) until the administrative
work is done. We have thus discarded laboratories from our
potential customer segments due to this problem.
Cost structure
Cost
structure
In order to carry out our business successfully, we have listed the various costs, both material
and human, that we must plan. First of all, there are the costs associated with the production of a
machine, which would have a unit cost in materials of €2,927.78. The implementation of such a
project also requires the provision of rent for a laboratory. In addition, it is necessary to plan the wages
of 3 employees; knowing that we take into account the fact that this figure will be revised upwards as
the company prospers. Other costs are to be expected, particularly with regard to the protection of our
product with the filing of a patent and a brand name. These are significant costs at the start of a
project, but they are essential to stand out from the competition and ensure that our value is protected.
It is also essential to provide for CE marking in order to allow the product to be marketed in the
European Union. Finally, for the first year, the expenses related to the company's registration must be
taken into account. Thus, if we take all these elements into account, the company's operating costs will
be €791719, 42.
We have planned not to sell any machines in the first year in order to carry out the various
tests necessary to obtain marketing authorizations. As a result, we will have a deficit of €795,000 at
the beginning of our second year. This deficit can be offset by raising funds or selling 5 devices for
167,000 euros.
Revenue streams
Revenue
streams
In the case of bacterial infection treatments, the most important cost for hospitals is the added
length of stay since it represents two thirds to three quarters of the overall extra charges. In fact,
"patients infected with multi-resistant enterococcus have a three and a half day longer intensive care
stay than patients infected with normal sensitivity enterococcus"[1].
Our device allows a faster diagnosis, and therefore a more adapted and faster treatment, thus limiting the
length of stay. The adaptation of treatment is part of the fight against antibiotic resistance, which causes
significant additional costs for hospitals. The extra charges of resistant bacterial infections averages
€1100 per hospital stay.[1] The treatment of sepsis costs 3000 euros per day of hospitalisation, which is a
significant cost and could be avoided with faster treatment. Finally, a 2015 report "All together, let's
save antibiotics" notes that "France spends between 71 and 441 million euros more than its neighbours
on antibiotic therapy in the city". Based on this data, we evaluated the price of our device to enable
hospitals to reduce the costs associated with bacterial infections, more precisely when they are
resistant. According to several sources, when looking at averages, the treatment for bacterial infections
costs 2000€ per patient per day[1]. Our device reduces the diagnosis from 4 to one day because
currently it is necessary to perform 4 blood cultures within 24 hours. Sometimes 2 blood cultures are
sufficient but to assess the accuracy and reliability of this method, 4 cultures are often required. Thus,
these 3 days of difference represent a cost of 6000 euros for hospitals. We took as an example the
CHU of Caen, which over 6 months, admits 1513 patients who are treated for a bacterial infection.
Therefore, over a year, and for 3026 patients, our device saves the hospital 18 155 000 euros, not to
mention the fact that the hospital stay will be reduced thanks to a faster treatment.
The presumption is that the price of our diagnosis will be 15€, which is lower than the price of a blood
culture. The diagnosis is faster, however, it allows a greater saving since the patient's stay time will be
less than 2 or 3 days. In order to determine the amount of our device, we used the following formula:
((Consumables lots per year / Number of tests with this lot) + (Price of the device / number of tests performed over the lifetime
of the device)) = price of the diagnosis
In order to determine the batch of consumables per year, we presume that the electrodes had to be
changed every 100 measurements, which corresponds to one change every 3 days, i.e. 120 changes.
We then divided this figure by the number of tests performed with these batches, i.e. 12,000 tests
(3026 times 4 (number of blood cultures per patient currently)). We then added the price of the
machine that corresponds to our unknown that we divided by the number of tests performed over the
lifetime, i.e. 12,000. The total amount must be equal to the price of our diagnosis, which is 15€
according to our hypothesis.
After solving this equation, we can ay that our machine will be sold 167 880 € i.e. 187437,85 $.
The first year we will not sell machines because we have to obtain the CE marking beforehand, so we will not receive any of this sales
revenue. However, we will be able to collect grants and raise funds. From the second year onwards, we will market the product and be
profitable from 5 machines sold.
Subsequently, we plan to integrate the rental of equipment into our business model,
particularly for humanitarian organizations with lower resources. Before that, we would like to enable
market entry in order to have enough income and a stable situation.
Thus, the diagnosis will have a reduced cost, but the hospital will mainly benefit from reducing the
patient's time of stay.
We have elaborated a new rapid diagnostic method,
used to precisely identify the strain causing an infection as well
as to follow the status of the infection by measuring the
concentration of bacteria in the sample. This will allow for the
determination of the efficiency of the treatment given to the
patient, and adapt it if need be.
Our method relies on the electrochemical detection of
bacteria, using carbon nanotube electrodes functionalized with
aptamers. Aptamers are single-strand DNA or RNA sequences,
allowing for the identification of specific targets through
binding properties. In presence of bacteria, aptamers will change
their conformational structure, thus modifying the close
environment of the electrode and enabling us to detect a potential
difference. This signal is linear with the logarithm of the
concentration of the bacteria, and this equilibrium between the
two conformational structures of the aptamers only takes a minute
to establish. We have integrated this technology in a new portable
diagnosis device, usable in both laboratories by research, doctors
or practicians, or even in harsh environment like in a
humanitarian context.
A refined design and advanced features allow for a
very simple use by any caregiver or doctor, without any expertise
in synthetic biology. For example, an automated measurement and
washing system will allow the physician to focus on the patient
after inserting the biological sample into the machine. After only
a few minutes, the result will be available and will allow the
doctor to make an effective diagnosis and treat the patient with
the appropriate antibiotic for the detected strain.
Market analysis
Medical diagnostic market
Our
study of the medical diagnosis market has given us insight on how
the legal aspect of diagnosis pricing is important. In France, a
typical diagnosis is composed of several minor acts that are
precisely described in the nomenclature of the Assurance Maladie
(main actor of health insurance in France). Thus, we have concluded
that today, the typical blood sampling and analysis for a suspected
infection can cost around 242.5 B, which corresponds to
approximately 65 € or 71 dollars. We have to make sure that our
device is able to answer all the characteristics of the detailed
procedures in order to reduce the cost of such diagnosis for
laboratories and hospitals.
Benchmark
Our
Several observations emerge from this inventory. First, we see that research is dense and diverse in the field of infectious diseases diagnosis. The identification of pathogens and their resistance to current antibiotics is as important as their treatment. A rapid analysis of patents citing “Antibiotic Resistance” and “Detection Bacteria” does not deny this trend.
Counts of patents granted and in application citing "antibiotic resistance" AND "detection bacteria", based on their publication date and jurisdiction. Graphs extracted from Lens.org
Secondly, it is important to note that the techniques that are currently in research or development phases use state-of-the-art technologies. These methods tend to be increasingly reliable and replicable but require a large package of scientific expertise. The devices developed are expensive and imposing but yet allow the analysis of a large mass of samples at a time.
The trend is obviously towards speed. Our observation shows that all the new techniques fall below the 10-hour waiting time for a result. This is therefore a necessary but not sufficient criterion for our proposition of value.
Finally, most of the devices described above are intended for use in hospitals or analytical laboratories. The development of these state-of-the-art techniques leads to machines that are imposing in size and therefore not transportable on less practicable terrain. Our proposal must highlight the fact that we want to adapt our device so that it can be used in humanitarian missions, with a minimum of consumables and as simple as possible to use. It means a lightweight device transportable by hand which fits in a shoe box, obviously robust, waterproof and with autonomous capacities when it comes to electricity.
