Point of Care(POC) Platform for Early Detection of Dengue

Bangladesh is currently reeling under an unprecedented Dengue endemic. Early detection (first week) is critical for its successful treatment and control. Current available rapid tests  cannot diagnose early stage infection while Hospital diagnosis is slow (takes 1-2 days) and resource intensive. The school going children are the most vulnerable population for Dengue.

We, collaborating with BUET ( Bangladesh University of Engineering & Technology),  propose to develop  a portable, fast (<20 minutes), accurate, simple and inexpensive Smart-Phone controlled platform, for reliable  early detection and screening of dengue fever. We propose on using this device to perform  screening  tests on school-children  in the Dengue  affected region.

Early  Dengue screening  with our device will substantially improve its treatment as well as  controlling its  spread . This would improve the general health of the Bangladeshi youth population, with considerably less financial strain on the Public Health Department.

Dengue, a mosquito borne viral disease, has affected 300 Million people world-wide, with about 96 million needing treatment and with 3000 fatalities.Widespread Dengue endemics are becoming alarmingly common in a number of countries including Bangladesh, which has been severely affected by Dengue in 2019 with Dhaka being the center of this epidemic. Till August 50,974  Dengue cases have been recorded by Bangladesh DGHS (60% from Dhaka). Surprisingly, this number is even more than the total number of Dengue cases recorded in Bangladesh from 2000 to 2018. In a 24 hour period  more than 7000 Dengue cases were reported. Sadly, 52 people, majority of them children,  have died from Dengue in Bangladesh in 2019. Currently, Dhaka  Hospitals have a total of 9000 beds and 1000 diagnostic centers, which is very inadequate to tackle this endemic.

·       Dengue has no vaccine or medication for treatment. Keeping the patient hydrated with enough rest is the only method for treating infected patients.

·       The severity of the infection increases substantially with the delay in treatment

·       Thus, early detection is the key for surviving and fighting this infection (only 1% mortality).

·       Current, rapid diagnosis methods mis-diagnose early stage infection.

Dengue disproportionately (80%) targets kids (15 or lower). Unfortunately, the kids are also more likely to die from Dengue. Since there is no medication or vaccination, early detection is the key for the patient to survive.

There are 4 types of Dengue virus: DenV-1, DenV-2, DenV-3 and DenV-4, of which Denv-4 is the has a 80% fatality rate. The first  infection is normally DenV-1, which has low fatality. However if the same patient is stung again, by Dengue carrying mosquitos, the virus mutates, and becomes DenV-2, which is significantly more potent . In this case the infection might lead to Dengue Hemorrhagic Fever which can turn fatal. Similarly, the patient gets exposed to DenV-3 and DenV-4 which are series infections. Ironically the DenV-3 and DenV-4 are very difficult to detect, particularly in the early stage.

We propose using our early Dengue detection platform to screen the  primary school students for DenV-1. If tested positive, they will be quarantined immediately , even before the symptoms of the illness have shown. So, this patient can recover without  the possibility of the virus mutating  to more potent forms. It would also control the spread of the endemic  to healthy population.

We have developed a novel POC Smart-Phone controlled quick Diagnostic platform/device.This patented device can quickly detect both bacterial and viral infection from biofluids (blood/saliva). The device uses Nanotechnology for quick detection, and Artificial Intelligence for in-situ data analysis.The tests are interfaced with an user-friendly Smart Phone App, which finally presents the results as one of 3 lights (Red–Positive, Green-Negative or Yellow-Repeat test) showing up on the phone screen.Thus the diagnostic test protocol is very simple and can be performed easily with minimal training. Since the test data is being acquired by a Smart-Phone, the non-personalized version of this data ( having qualifiers like age, sex and location details)  can be instantaneously uploaded in the cloud. The cloud data can be subsequently shared with the Department of Public Health as well as local Hospitals  so that adequate amount of resources can be targeted to the  infected region thus helping in controlling the endemic.

We currently  have a  working prototype of this device . The device has been tested on animals for early  detection of an animal virus of the Arterivirus family .The results have been validated with standard RT-PCR measurements. This is a single stranded RNA virus similar to the Flavivirus family which causes Dengue.  Since our device works on the principle of detecting DNA/RNA hybridization we expect that we would be able to detect Dengue (with only minor adjustments). Our device uses a “Razor & Blade” model.  It has a tiny controlling console (interfaced with the phone “Razor”) and each measurement is done with “use and throw” strips (“Blade”).

Having tested our device for detecting Denv-1 from blood samples, in collaboration  with BUET we propose the following

·       Run a Beta Dengue screening test at a primary/secondary school in the Dengue affected region of Bangladesh. Dengue has an incubation period of 7 days so the entire school  will be tested once every week. A student would be quarantined on testing positive and immediate medical care would start. Additional testing would be performed on the locality from where the positive tested patient comes

·       BUET would  simultaneously run a series of training modules to prepare the personnel for performing these tests. They will conduct conferences to make the Medical community aware of this disruptive technology and how to interpret results

·       Subsequently, our Bangladesh collaborators would develop upgrades for detecting Denv-2, Denv-3 and Denv-4

Molecular Biology based technologies have  currently revolutionized  medical diagnosis.The sample size and the speed of detection have been improved by using Nanotechnology. Different solutions are being proposed using these new technologies. Some of the current established molecular- diagnostic technologies  are RT-PCR ( Real-time Polymerase Chain Reaction), ELISA ( Enzyme Linked  Immunosorbent Assay), FISH ( Fluorescence In-Situ Hybridization), LAMP ( Loop-Mediated Isothermal Amplification)  . Majority of the current diagnostic innovations are  improvements on these methods but still using the old technology as base and so  these are  “incremental technology”

Our method is unique, novel and totally different from these incremental methods. It is Disruptive. The major  difference of our method is that we can detect hybridization of entire genomic DNA in one shot,  thus eliminating the need of sample amplification which is a necessary step  for all the  other methods. It quickens the process, and significantly  improves  the  sensitivity and specificity of our device .  Another unique feature of our platform,  is that it label-free and hence can be used for detection of viral-bacterial infection inclusive of mutations. Finally, our device  is a product of  Multidisciplinary team effort   including  both Nanotechnology ( for generating the signal)  AI (for analysis) and Integrated Knowledge Based Technology ( web-BOT)  (for quick dissemination of the information in the web , thus providing Public Health experts ammunition to fight fast spreading epidemics like Dengue). The technology  is also  protected by 2 approved  and 2 pending world/US patents

Dengue is currently a fast spreading endemic in Bangladesh stretching the ability of its Heath care Department . The lack of medication, makes early stage detection the key requirement for Dengue survival.  Majority of  current diagnosis methods cannot detect early stage infection. kids (under 15 year old)  are unfortunately the most susceptible population.

We have developed an unique and disruptive  POC Diagnosis platform/device that can detect early stage bacterial/viral infection in 20 minutes. The  data is analyzed using Machine Learning Algorithms using a simple user interface with a Smart Phone App.  Hence the device can be used with minimal training. Anonymized diagnosis data along with location information can also be shared with the Public Health personnel, real-time,  for efficient allocation of resources to stop the endemic.

We have a working prototype of this device, which has been tested for detecting  early stage Animal viral diseases and e-coli from water and food. The results have been validated with standardized RT-PCR. The sensitivity and specificity is significantly better than current methods. Numerous articles have been published on this technology on referred journals and conference proceedings.  The technology is also  protected by approved and pending  US/world patents.

After validating our technology for early stage Dengue virus  detection, with collaborators from BUET, we propose on performing once a week screening tests on primary & secondary school students during the 4-6 months Dengue season. A patient with positive results will be immediately quarantined and put under medical care.

Currently our device is not being used for diagnosis of people as it is still undergoing development.We have successfully performed animal tests.  We propose on having a system for performing Beta test by screening  primary school children in the Dhaka by the end of the first year.  

The population of Bangladesh is 150 million and 40% (~60M) is below the age of 15. Bangladesh is experiencing rapid urbanization and so the population of Dhaka is growing rapidly ( 20 Million in 2019) straining its infra-structure creating a large number of slums (~5000) around the city for the migrant population. Dengue endemic is spreading like wild-fire in these slums. Thus we plan to choose a primary school in one of these slum neighborhoods for beta testing. Each of these schools approximately have 5000 students and that would be the number of kids we plan to serve in the first year. Screening a kid directly impacts the family members and so assuming a 4 member family the first year impact would be about 20,000 people.

Dhaka  has 295 government and an equal number of private  primary schools graduating approximately 1 Million students every year. There are another 0.6 million secondary school students graduating every year. At the end of five years we anticipate screening all the Dhaka area primary and secondary school kids ( ~15 million). Assuming, once again the immediate  4 family members of the screened kid, our Dengue test would  impact 60 Million people in five years.

Work in collaboration with faculty  from the Department of Biomedical Engineering Department in BUET (Drs Ferdous, Arafat and Hasan). 

·       First year 

o   Validate  the diagnosis prototype with water-borne bacteria currently being cultured in Dr. Arafat’s lab

o   Develop extraction  protocol to make the device applicable for Denv-1 by Drs. Arafat and Ferdous . Denv-1 culture to be obtained from Dhaka Medical College (DMC)

o   Dr. Hasan develops the  preliminary Machine Learning (ML) model and Android App for the data analysis and the group validates it for blood samples from patients at DMC

o   Run Beta-test on the prototype by using it to screen kids at a Primary school in Dhaka

·       2nd year

o   Dr. Hasan improves the ML model with the new data from the beta-test. 

o   Drs. Ferdous and Arafat develop simplified protocol for extracting Denv2  RNA from blood samples and Dr. Taufiq develops new algorithm for Denv-2  

o  This leads to the new prototype

·       3rd year

o   R&D  continues for improving the prototype for  detecting Denv-3 and Denv-4 .

o   Training courses organized at BUET for teaching  the new screening tests all over Bangladesh. The screeners and the primary schools will be awarded incentives based on controlling the Dengue endemic. 

o   Establish manufacturing facility for testing strips in Bangladesh.

·       4th &  5th year

o   Start a  Bangladesh branch of 12-15MD.  This facility will perform R&D related to Dengue and develop better ML algorithms.

Our technology is unique, disruptive and different from the current method of Dengue diagnosis treatment and control.  Our platform is for screening the Dengue virus, for the most susceptible population – primary/secondary school students. Each and every kid needs to be tested periodically ( once a week) and quarantined as soon as found positive. The symptoms of the disease ( e.g. high fever, weakness etc.) may or may not show at this early stage. However, if the patient is quarantined and treatment is started at this early stage the mortality rates are extremely low (~ 1%) . Also it prevents the infection from spreading to others  and thus decrease the chances of it growing to an endemic.

Since our protocol is  different, both the health professionals and the general public needs to be made aware of this new protocol – particularly highlighting the benefits.  The health professionals and the public have to be willing partners for the success of this solution. We feel this is a barrier which needs to be overcome.

Another barrier would be the efficiency of the implementation of this  school student screening  protocol.  This is particularly challenging to a densely and heavily populated  resource strapped country like Bangladesh.

·       Reputable US  institutes  like University of Connecticut, University of New Haven as well as that of Bangladesh like BUET and Dhaka Medical College and Hospital are our partners in this solution.  They will validate our results and also present it  in Technical/Medical conferences and journals  .

·       We  propose,  organizing  periodic information sessions and  training modules  with the help of our partners initially in Dhaka and then all over Bangladesh.

·       We propose on having partnerships with large NGO’s like “BRAC” and “Save the Children”   for  using their resources for raising public awareness as well as implementing the screening tests nationwide.

·       Develop partnership with the Department of Public Health in accessing  their public service platforms for spreading awareness of this new method.

·       Use Social media platforms like Whatsapp , Facebook, Instagram , Tweeter etc.

·       We will develop “webBots” in our interface app which will help us in efficiently targeting  our solution,

·       Develop a reward/bonus policy used to incentivize the awareness. The screening of primary/secondary school kids would be benchmarked to the decrease in the incidence of Dengue in that region. The screeners will be rewarded if they can meet these benchmarks based on statistics from independent organizations like ( UNESCO, WHO etc)

·       We hope the efficient control  and gradual eradication of Dengue endemic in Bangladesh  will be the greatest advertisement of this solution.

The first 3 years will be consumed in developing the final product that can diagnose all four Dengue viruses .  In Bangladesh this development would be primarily done at BUET in collaboration with DMC.  We expect to start a production facility ( for Bangladesh market) in year 4 and have a branch office to handle the technical issues and product upgrades in Bangladesh by year 5. Both these facilities will generate low, mid and high level Engineering/technical jobs. This expansion plan is based on  our product having a large market opportunity in Bangladesh and at the end of the 5th year we anticipate in penetrating the South-Asian Dengue diagnostic market with Bangladesh as the base.

Our solution, the Diagnostic platform works on the “Razor-Blade” model. The console (in this case the Razor) can perform several measurements and has a life-time of 1.5 years. It interfaces with the Smart Phone App. It however needs to be upgraded periodically with the latest version of the apps. It is estimated that on an average  every participating school will require 4/5  ( one for each Grade) of these consoles.  There are approximately 10,000 primary schools and 7000 secondary schools in Bangladesh educating approximately 30 million children . Assuming a console price of $100 the total addressable console market is The total addressable market (TAM) in Bangladesh for the consoles will be $8.5M. Assuming $5 a strip ( lower than the current  Dengue test cost) the  conservative estimate of TAM for strips is $3Billion/year.

12-15 MD  has a multidisciplinary team consisting of Scientist, Engineers, Doctors and Business Professionals.

 It currently has 2 Full-time and 4 part-time employees in addition to the 7 manager/Advisors. During summer months we regularly hire 4 interns to assist us.  The minimum qualification of the staff is MS. All the Manager's/Advisors have Ph.Ds . We  also have 2 Medical doctors ( MBBS and MD) in our team . Our team consists of 2 very experienced Business professionals  who have personally founded Billion-dollar  high-tech companies. 

Dr. Saion Sinha ( CEO/President) :  20+ years experience in Nanotechnology & Biosensors   Has 50+ publications with 1000+ citations , 7 patents, $1M+ research grants. Nominated for Blavatnik award (NYAS) & Connecticut Medal of Science. Has Ph.D.in Physics from University of Kentucky, and BS  and MS from Indian Institute of Technology

Dr. Ewa Kirkor ( CTO) :  Is an inventor with expertise in  Nanotechnology . Has 30+ years experience at Dupont, Analytica, Univ. of Illinois-Urbana Champaign and University of Texas-Austin. Has Ph.D. from Polish Academy of Sciences

Dr. Ali Senejani ( CSO):  10 + years experience in Molecular Biology and Genetics from Yale University and University of New Haven  with 20+ publications .Has MS from University of Manheim and Ph.D. from University of Connecticut

Dr. Said Mikki ( CIO):  10 + years experience in Antenna Theory, Machine Learning and Artificial Intelligence from Royal Military Academy, Canada and University of New Haven .Has 50+ publications and 3 book chapters.  Has Ph.D. in Electrical Engineering from University of Mississippi

Dr. Santanu Das ( Chair of Board)   40+ years experience in leading Hightech companies.  Founder of TranSwitch Corporation ( $5Billion market value).

Dr. Yaw Adjepong ( Medical Expert)  30 + years experience as a Medical doctor specializing in Internal Medicine and Pediatrics  at Yale University College of Medicine. Has MD, MPH and a Ph.D.

Dr. Barun Kar ( Board Member)   20+ years experience in starting high-tech startup companies. Senior VP and founding member of Paloalto Networks (NYSE-PANW).  

We are collaborating with faculty members of the Department of Biomedical Engineering at Bangladesh University of Engineering and Technology (BUET). The members include Dr. Mohammad Tarik Arafat, Dr. Jahid Ferdous and Dr. Taufiq Hasan. BUET will coordinate the efforts on blood sample collection from Dhaka Medical College with the help of Dr. Mohammad Robed Amin, Department of Medicine, DMC.

• Year 1

• • Validate the diagnosis prototype with water-borne bacteria currently being cultured in Dr. Arafat’s lab
  • Develop extraction protocol to make the device applicable for Denv-1 by Drs. Arafat and Ferdous. Denv-1 culture to be obtained from  DMC
  • Dr. Hasan develops the preliminary Machine Learning (ML) model and Android App for the data analysis and the group validates it for blood samples from patients at DMC
• Year 2
  • Dr. Hasan improves the ML model with the new data from the beta-test. 
  • Drs. Arafat and Ferdous develop a simplified protocol for extracting Denv2 RNA from blood samples and Dr. Hasan develops a new algorithm for Denv-2. This leads to the new prototype
• Year 3
  • Drs. Arafat, Ferdous and Hasan develop the updated version of the device capable of screening for  Denv-1, Denv-2, Denv-3, and Denv-4 – all forms of Dengue.

Our Dengue screening platform/device is similar to the Razor-Blade model. The measurement is performed by a Smart Phone interfaced console.  To perform testing, specialized chips are required to be mounted on the console on which the sample (blood or saliva) loaded. They are disposed of after the completion of the test.

Thus we have two revenue-generating products – the console and the strips. The console revenue is negligible compared to the strip revenue.  The annual revenue for the total accessible Bangladesh market for the console is $5.67 Million and $3 Billion for the strips. Thus, as an incentive, we propose donating the console to the different school systems free of cost. Conservatively assuming a 10% market penetration by year 5 we would be earning $300 Million for the strips. This revenue is not expected to have big seasonal fluctuations. We can grow the revenue 4 times, by expanding the screening protocol to include the immediate family members of the students.

We plan on putting Bangladesh earned revenue back by building a strip manufacturing facility and a service center in Bangladesh. This will help us improve our customer relations, a definite requirement for the success of our business. It is expected that these facilities would generate high-paying responsible jobs.

Dengue is a big problem in a number of other South Asian countries like India, Myanmar, and Thailand. In the future, the Bangladesh service center can be central to this expansion.

12-15 MD is a US startup incorporated in Delaware in October 2016. In the US we have targeted the farm-animal market for our patented and prototyped diagnostic platform . The company has been funded by Angel Investors and some Government grants up-to this stage.

 We propose on modifying  our current animal- diagnosis  prototype and use it for screening and controlling Dengue fever in Bangladesh initially  and a number of other countries later. The initial funding from the Tiger IT foundation would be utilized in developing a  working prototype for  Dengue screening and running beta-screening at a Dhaka area primary school. Since this is a disruptive technology part of the initial funding would be used in incentivizing the population as well as making them aware of our solution. From third year onwards we would be able to market a screening device for Dengue in Bangladesh. This two part device, with a  permanent measurement console ( initially distributed free for poor schools)  and the consumable testing strip which would be manufactured in Bangladesh. The strips are planned to be marketed at $5 a pack which is lower than the cost of ($7)  government subsidized dengue diagnostic test . Since this is a screening device the strip market would be exceptionally large with a revenue of $ 150 Million ( assuming only 10% market penetration) . This revenue would self-finance the company . More revenue can be made by trying to capture the south Asian market.

Dengue is a currently a devastating endemic in Bangladesh. Our solution is to use a disruptive technology to screen people and thus create significant impact in the treatment and control of the endemic.

The funding will help in developing a commercial Dengue screening device from our existing  animal- diagnostic prototype

As described earlier there  are two major barriers for the successful implementation of this solution in Bangladesh.  Since our solution is disruptive it would require to raise awareness to the   the medical community and general public  about its advantages. In this case the Tiger Challenge funding will be used to run a beta-screening test at a Dhaka area primary school for the entire Dengue season.

The second barrier  to overcome is the issue of the logistics of running such a large screening program in a densely populated country like Bangladesh. The Tiger Challenge funding will be used to incentivize the people with a reward scheme which will be  benchmarked to the control of the Dengue endemic.  Tiger Challenge would also able to provide contacts with non-profits ( NGO) like BRAC and "Save the Children" who have considerable experience in running similar programs in Bangladesh.

Our solution involves significant amount of Information Technology (IT). The sharing/gathering  of non-personalized patient information efficiently across Bangladesh or other countries is a big IT project. Since Tiger-IT has expertise in implementing large IT  programs in Bangladesh we hope that we would be able to get help and advice from them .

BUET is our primary partner/collaborator in this project. We would also be collaborating with DMC through its MOU with BUET.

For accelerating the implementation of our solution we plan to partner with NGO’s like “Save the Children” and BRAC. These organizations are experienced in running   similar screening programs  like the “vaccination drive for children”.  The implementation of our solution --- the screening of primary School children for Dengue requires expertise in running similar programs . One of the plausible options is to outsource the implementation to these  NGOs.

We are solving a public health problem where the entire population will be impacted. Resources have to be  quickly allocated to nurse/treat the patients who tested positive in the screening test. They also need to the quarantined. The Department of Public Health has its expertise in this area . We plan on partnering with them so that we can complement their expertise and work together in controlling this deadly endemic.

A partnership with the Department of Primary Education is also being planned . This will help us in obtaining information about the timing and other manpower resources that will impact our solution.