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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 45 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

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

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 500 mL (15x10x5 cm3). 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 patients. Once the sample is inserted into the device, a pump will mechanically push the fluids 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 diagnosis to remote populations in hard-to-reach areas.

Customer relationships

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

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 field of infectious diseases, 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. Agnès Durand 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

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.

¹ http://www.infectiologie.com/UserFiles/File/medias/enseignement/gericco/2015/2015-Gericco-Hemocultures-Dargere.pdf

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.