COVID 19 Fast Self-Test & Tracing Option

Contagion control is essential to limiting impact of COVID 19 (SARS-CoV-2) continuing pandemic. Fast and simple self-test with BioNanosensorTM  from 12-15 Molecular Diagnostics  enables low-cost diagnostics and  spatiotemporal virus tracking  option to user-authorized  decision makers anywhere.  BNS gives clear-cut, yes, no,  or rarely 'repeat test' report on presence of COVID19 genetic signature in saliva. Our novel use of nanocarbons for signal generation integrated with machine learning and information technology forms the platform for point-of-contact detection of sensitive and specific molecular genetic signatures of organisms of interest in a wide range of fields. The prototypes were validated  on a related virus. Order of sensitivity for E. coli  is about 2 bacteria per 10  micro-liter sample. Our platform is poised for field detection of SARS-COV-2 and other microbes in  minutes.

The global scale-up of BioNanosensor  has potential for solving  the unmet need for containment of infectious human and animal diseases.  

Globally the numbers of COVID-19 cases grow in millions in spite of containment efforts. The US remains the epicenter and  all are affected by work disruption, school and business closures and severe limitation on all gatherings. There is potential for overload on health services. Availability and accuracy of testing is insufficient for rational management of resources.

BioNanosensor solution will increase by the millions availability of sensitive, accurate, quick and simple testing for COVID 19. Test users will learn about their infection status and get follow-up care. Contagion tracking authorities will get real-time  information about local distribution of the virus  such that rational decisions about containment efforts  and resource allocations can be made on granular scale, from the individual to contacts, specific business, services, or schools, to a neighborhood, district, township, and further  to county, or the state. 

These partial solutions will be better enabled:  care for the individual, protection of the service providers and society from exposure,  and rational implementation of  quarantining restrictions, and distribution of resources.

Using saliva directly with BioNanosensor(TM) (BNS) prototype detects trace COVID-19  viremia in about 15 minutes. BNS has 2 parts: a single-use sensor, and a repeat use Smartphone/Wi-Fi/internet enabled signal transducer with a deep learning algorithm (AI/ML) for diagnostics. The sensor's genetic probes assure detection specificity together with negative and positive controls. Deposition of the user's saliva initiates acquiring direct electrical signal and processing by the transducer evaluating hybridization of complementary materials at the sensor. The recorded derived information is shared in real time according to user's choice  of recipients. The user can obtain the result directly through the transducer interface or the  web or smart-phone app by intuitively-colored signals: red - infected, green - infection undetectable, rarely - yellow - result inconclusive. Result sharing enables healthcare and contagion management options.

BNS prototypes are entering training with clinical samples with probes specific for SARS-COV-2. Training  for accuracy of no more than than 5%  false negatives or 5% false positives at 95% confidence requires about 500 tests. SARS-COV-2-validated and FDA cleared, the instrument will be productized and launched.

We validated BNS on several other targets. A related virus is detectable 4 days after inoculation and 3 days before disease onset. 

On the individual level, this solution can be available to any person  who wants to know if they are infected by COVID 19 either  by use of mobile or stationary testing stations. On the community and government levels the information on the spread and progress of the infections can be used for  a range of decisions impacting the provision of health services, education, conduction of business, and everyday life. The Team follows these events on the local, national and global and communicates with local representatives of all levels of organizations engaged in limitation of extent of damages related to this pandemic.  We count on the solution to help reduce the threat to manageable level within months from adoption.

The challenge is

The rapidly spreading COVID-19 is a global threat with high mortality for the elderly, institutionally confined, and service providers such as healthcare workers.  About 52 million Americans are 65 or older (U.S. Census 2018), placing them at high risk. This pandemic has also caused significant disruptions to the economy and daily lives of multitudes Our solution will lead to rapid diagnostic improvements and significantly reduce the spread and mortality of the virus at all age groups, enabling a faster global recovery.

 

The benchmark virus detection is qRT-PCR, at best giving results for SARS- COV-2 in 45 minutes from sample introduction to result. It normally requires expensive reagents and specimen pre-processing by qualified personnel in a dedicated lab. The result from BioNanosensor have comparable accuracy and precision of results. The testing does not require pre-processing of samples  or assistance of personnel with specialized qualifications. There is a number of test that are rapid and direct, but do not have comparable sensitivity or accuracy. As far as we know, none of the competing products can match all the features present in the BioNanosensor. The most important of these  are high sensitivity, specificity and minimalization of false positive and false negative results. 

The high quality of results combines with the real-time sharing of results among the user, user's healthcare provider and a contagion managing agency can deliver:

earlier and more appropriate healthcare for the user, 

protection of the most vulnerable from the contagious;

improved timing, selection and localization  of contagion prevention measures 

more precise deployment of resources for abatement of consequences of the pandemic 

 Ease of use  and privacy protection as illustrated by the BioNanosensor smartphone app interface

At the core of BNS is the recording of the electrical signal evolution upon  application of the saliva specimen onto the sensor containing appropriately selected embedded probes and the occurrence of probe hybridization with the genetic material of the  target microbe in the specimen. This signal is interpreted by a machine learning algorithm with accuracy and precision dictated by the extent of training and validation. The specimen acquisition is  noninvasive. Signal generation is direct and fast. The user is guided by instructions provided by the instrument interface assuring informed consent. There is no need for specialized personnel assistance. The built-in programming enables archiving and sharing the derived data in real time with user-designated recipients, leaving control of users privacy in the users hands, important factor in the US culture making the solution acceptable to a large fraction of the population. This feature  is important to solution effectiveness, as the USA remains the center of the pandemic and  that COVid-19 infections will likely continue for some years  with intensity dependent on the extent and persistence of acquired herd immunity.

The business model involves the repeated sales of the disposable sensors and repeat-use transducers. Healthcare providers will have priority of acquiring BioNanosensor kits through medical equipment distributors. The animal testing application do not require FDA clearance, so these are a part of the business plan assuring business sustainability and constituting initial proving ground for further human applications. Expansion to testing for several co-infection are planned.

 

A product prototype demo is available here

 video https://www.youtube.com/watch?time_continue=43&v=OsfeHcQn1Kk&feature=emb_logo

The BNS™ system prototype uses a few disposables: a sample collection pipette, 6 sample receiving chips, a negative reference chip and positive reference chip. In the final product a single specimen application will suffice.  

Detection of the  SARS-COV-2 RNA with BioNanosensor(TM)The genomic target specific sensing, either RNA or DNA, was demonstrated on a variety of microbial oligonucleotides and genetic materials from plants, animals, and humans. Probes can range from a few tens to several thousands of nucleotides; longer probes deliver higher specificity.

Representative Results for SARS-COV-2 N orf RNA:  Positive Result  (Top) for 10(exp -14)M RNA  and CDC approved probe;  Negative (Bottom) for  same probe concentration but a non-COVID RNA.

The BNS™ signals the presence of short synthetic representative sequences of SARS-CoV-2 within 200 seconds (3.5 minutes), the total time from sample application to the end of the signal evolution is about seven (7) minutes. Dilution experiments indicated COVID19 RNA detectability at 10(exp-18)  Molar concentration

Demonstration of Porcine Respiratory and Reproductive Syndrome virus detection: 

Demonstration of detecting a bacterium: E. coli in lettuce

Testing by individuals will give them information about contagiousness and, if  contagious but ambulatory, rationale to control their behavior so to limit spreading the virus.

For healthcare providers, it will give them tool to monitor their patients and initiate timely treatment prospectively limiting the infection progress.

For the healthcare workers, workers at nursing and other confinement facilities,  it will give them tool to monitor  their status and effectiveness of preventative measures in high risk of exposure environment .

For the institution tasked with devising and implementing measures limiting the contagion and making decisions about distributing resources it will provide timely and specific information base for targeted actions.

In consequence the society and individuals will benefit:

With wide deployment of accurate testing within next six months there is potential that our testing solution will help limit the spread, intensity  and duration of the epidemics. Consequently, the morbidity and mortality will be limited. The resources will be used more effectively. The behavioral restrictions will be focused where needed and overall less onerous and  economic effects will be less destructive .

At present the solution is in internal test to the extent permitted for testing the solution. This involves less than two dozen individuals.

During clinical testing it will involve up to a 10,000  anonymized individuals, if sample pooling is used for clinical validation. Sample pooling decision awaits strategic evaluation.

In the launch phase we envision two orders of magnitude expansion of the reach of the solution.

Since some individuals will require repeated testing to follow their viral titers and infectivity, we anticipate that about a million individuals a year will use our solution with direct effect on the course of their healthcare delivery. We hope that going forward we will be able to return to focus on the animal health and microbial purity of foodstuffs, that our solution was being developed for in the first place. As far as human needs go, we will consider simultaneous testing for co-infections. We know such development is possible and we are asking for  your input in the evaluation of such option

Most immediate goal is to drive this solution through clinical validation in the next 3 months, then pilot manufacturing and launch with marketing to most strongly motivated customers, that it the healthcare providers and organizations.

Given the nature of the COVID19 disease, features of our platform,  and the solution it will be natural to expand the product capabilities to differential testing for other viruses, and probable secondary co-infections occasionally complicating recovery from the initial insult. We will consider licensing the use of the platform for manufacturing derived products within geographic areas where the disease is prevalent. As future development we envision progress to having the device certified as low complexity for home use in conjunction with internet-enabled medical services.

We are planning expanding into farm animal testing market  where  we have gained initial traction.

Although the competition is numerous, the demand for testing is stronger, the  testing kits supply remains insufficient, and so is the testing quality. 

The legal barrier for our solution  is the lack of certification.

The pre-certification validation and conforming to the FDA requirements documentation of our solution is necessary. It  relies on conducting numerous and diverse enough clinical tests, so arranging and financing  for dual, parallel testing with our BNS and with a benchmark RT-PCR is a limiting factor.

Assuming we will obtain the right to market our solution, we need financing for the development of pilot production.

The barrier to acceptance of information sharing with our solution is a defiant rejection of the need for contagion prevention measures such as quarantining, or visible measures such as wearing face masks in public.

Even if the individual user disables information sharing features of the solution,  the individual will have reliable information to implement helpful self-care measures and at least derive a partial but substantial benefit. 

 

We are informing prospective customers about our solution.

We are fabricating  transducers and sensors  and  having prospective customers compare our solution with alternatives;

We are expanding our facilities and our staff;

We are forming alliances within the supply and service chains founded on mutual agreements specifying work products, rights and obligations of each party.

We are conducting research, development and marketing according to priorities and milestones  developed with assistance of our board of directors, partners, advisors, and hired experts as needs arise.

 We are are looking for director of operations experienced in launching start-ups,

 We are looking for clinical testing director for planning  and documenting concurrent standard and bionanosensor  clinical testing in parallel.

We  have arranged for contracting  biostatistical assistance with organization and  interpretation of the clinical tests.

We are arranging for  enterprise resource management in anticipation of pilot product introduction and further scale-up.

12-15 Molecular Diagnostics, Inc. is a privately owned business in development organized as  for profit corporation. It is not a subsidiary of any larger entity. 

However, 12-15 Molecular Diagnostics,  serves as a center of associations of independent small  businesses coalescing into a system of alliances enabling generation of the solution.

There are partners working at the 12-15 Molecular Diagnostics, one part-time, and one full time. The company has been employing three full-time staff specialists, and one part-time staff specialist, a manufacturing technician is being hired. We plan hiring 2 contract manufacturers one for productizing and mass-manufacturing of the sensor and another for productizing mass manufacturing transducers, a FDA clearance consultant and a BioNanosensor kits and sensors distributor.

More workers or contractors will be employed as the 12-15 Molecular Diagnostics growth permits.

The 12-15 MD Stellar Team  covers business and technology in biomedical engineering, molecular biology, material science, and IT. The solution's versatility,  adaptability  and cost effectiveness moderates risks. Ex-vivo animal test has been successful.  The commercial interest arose with the success of detecting porcine respiratory virus in serum and saliva, E. coli in lettuce and other microbes in a variety of media. The 12-15 MD is  stepping up to focusing this technology on detection of COVID 19 within a few months. Our partners vetted us over the years and provide support for productization of BioNanosensor. The team continues working productively over several years. The pandemic made us more cohesive and dedicated to achieving the solution. Our work is described in peer-reviewed publications and patents: 

• S.K. Jasti, S. M. McGinley, F.Pena, S. Opper, E. S. Kirkor, S. K. Sinha “Substrate Optimization of Carbon Nanomaterial Based DNA Hybridization Detection System.”; Biophysical Journal, 114(3): 686A, (2018)
• N Farzad, S Opper, K Taisma, ES Kirkor, A Senejani, SK Sinha; "Highly Selective Bionanosensor for Quick Detection of Bacterial Pathogens in Food." Biophysical Journal 116 (3), 316a, (2019)
• MT Maung, S Opper, K Taisma, ES Kirkor, A Senejani, SK Sinha; "In-Situ and Quick Detection of RNA Virus by Nanobiosensor."  Biophysical Journal 116 (3), 444a  (2019);
• US Pat. # 8,623,509 ‘Thermometric carbon composites’ 1/07/2014
• Bionanosensor detection device; SK Sinha, ET Sapi - US Patent 9,919,922, 2018 

 Continuing funding by individual investors expresses trust in our results and capabilities. 

The partners support us with materials, business information, parallel testing, access to their test and production facilities, and hundreds of thousands of dollars worth of work-hours either already spent or committed. When they sell their products or services to us they charge these at cost. We reciprocate  with our services or expertise when appropriate.

Their logos are displayed on  the 12-15 MD website, see the https://www.12-15mds.com/.

We have entered into collaborative agreements with defined rights and obligations. At present we work together by telecommuting and exchanging materials by designated commercial carriers.

Healthcare workers are under the highest pressure from the threat of contracting COVID-19. They will be the primary recipients of our solution.  The model can be sustainable as in the following example: There are about 6000 Hospitals, 8000 urgent care facilities, and about 250,000 professionally active primary care physicians in the USA. First-year marketing will mainly focus on and is assumed to attract from 0.1% to 0.5 % Individual Primary Care Physicians, US Domestic hospitals and urgent care facilities. The expectation is the sale of 288 to 1,440 devices at introduction. Each detector will average 30 tests per day, and will be used for only 100 days (~3 months) of the year. Main revenues will come from repeat purchase of supplies for the detectors in the hands of our customers.

Potential 1st Year Revenue Estimate (US Domestic) at 0.1% to 0.5% market penetration :

Market Potential/ year

Device unit sales

Device Price

Device Revenue

# tests / device

Supply units sold

Price / test

Supplies Revenue

Low Rev

288

$2,050

$590,400

3000

864,000

$39

$33,696,000

High Rev

1440

$2,050

$2,952,000

3000

4,320,000

$39

$168,480,000

Potential revenue would triple at increase in market penetration from 1% to 5% when economies of scale combined with business sustainability would permit unit price decrease:

Market Potential

Device unit sales

Device Price

Device Revenue

# tests / device

Supply units sold

Price / test

Supplies Revenue

High Rev Case / year

14,400

$499

$7,185,600

3,000

43,200,000

$14.99

$647,568,000

We are applying for grants from a variety of sources and combining self- funding , support in kind from partners and equity funding from individual investors. Now we must focus on obtaining necessary clearances for human use of our solution. We plan to support solution sustainability by  deploying it to infection detection  it in the already prepared animal market. Essentially we are looking for alliances, capacity  and means to reach the human users of our customers (healthcare and other social services providers) at a socially meaningfully large scale so that COVID19 can be contained and consequences of the pandemic abated wile charging somewhat less than our competitors, and delivering more valuable products. That we can do so, we have compared our  prototyping costs to  the unit value  and scale of RT-PCR test to our commercial animal farming customers servicing over 1 % of their market.

12-15 Molecular Diagnostics sees urgent need for solutions to the raging COvid19 and possible future epidemics. The need is obvious and we want to help solve it. We evaluated our solution against existing testing options and concluded that even in the presence of existing competition the needs is so large that there is demand for 'all hands on deck'. Moreover, our solution appear to be more agile, high quality, faster and economically affordable for a wide range of applications. 

We want to enter, interact and contribute to  the community of solvers

 We have organized supply, manufacturing, clinical testing and product distribution chain in order launch the product solution. We are looking for additional validation of our funding and revenue model  from experienced in molecular genetic testing parties.

 We are looking for fulfilling the need to access to clinical testing laboratories and partnerships

 We have identified the crucial partners within the material supply chain , tested the materials and found treasonable assurance of availability, quality and continuity of our supply of materials.

We have unfulfilled need for documentation of the device development and tests compliant with FDA requirements. We need guidance and funding for fulfillment of this requirement for regulatory compliance, as much as for attendant monitoring and evaluations.

In addition to funding, 12-15 Molecular Diagnostics is interested in collaborative agreements and introductions to potential users to form user panels and receive feedback from a wide range of BNS trial users. We are also interested in potential for licensing the solution to other organizations. 

The can be transnational and  globally transformational   if scale-up  spreads beyond the borders of the US to places such as  Bangladesh, India, Africa , if we are awarded this prize we will use it to reach out as well to our  neglected segments of the society and deactivate the superspreader centers. We will make effort to make air travel less prone to dissemination of infectious diseases,  and to make schools less like Petri dishes for incubation of infections.

Several essential to developing the the solution team members  are women who contribute inventions, ideas, discoveries and high level skills to the development of this solution. The direct COVID19 victims, are mostly men (now about 70% of the 8 million people globally), the numbers of sickened are rising, and the devastating economic burden falls predominantly onto the women pushing them and their children  down into desperate conditions   thus defeat of this contagion with help from this solution deserves the Innovation for Women Prize.

COVID-19 is a directly transmitted infectious disease due to SARS-Cov-2 RNA virus where primary factors shaping the epidemics are susceptibility to the infection and patterns of connectivity among individuals. Projecting recurrences of COVID-19, epidemiologists point out that North America currently is and in future will be the epicenter of such pandemics and long-term containment measures will be needed. Low sensitivity of current tests makes it difficult to detect SARS-Cov-2 and confirm that a sickness is due to it because about 30% of results can be false negatives. Older than 50 individuals are the most susceptible 20% of the US population.

The 12-15 Molecular Diagnostics intends to reach millions of individuals with its solution. The solution for the COVID 19 is a small fraction of the potential of the platform that supports it.  The COVID 19 detection solution embodied in the BioNanosensor™ (BNS) has these features:

• Test is noninvasive, easy to self-administer with minimal instruction provided by prompts from the instrument, under supervision if required 
• Saliva specimen is used to meet the growing diagnostic demand. Saliva proves to be an appropriate specimen in many infections.  
• User obtains result in minutes. The result shows as one of three intuitively understandable indicators (Red light – infection positive, Green – infection negative, or Yellow - repeat test).
• Diagnosis is accomplished by an AI/ML (Artificial Intelligence/Machine Learning) algorithm – No expert medical professional is required. Telemedicine can be implemented.
• Measurement data, time, place, user information and test result are simultaneously uploaded to a secure repository web site and derived data are sent to authorized decision makers.
• BNS is protected by granted core patents:  device (US Pat. 9,919,922) and composition of matter (US Pat. 8,623,509).
• There can be an option for detecting multiple pathogens simultaneously.

The BNS concept applies to detection of various genetic materials in a range of biofluids. It has been vetted on DNA and RNA targets in a range of situations, including  validation with Porcine Respiratory and Reproductive Syndrome virus, (PRRS) in  pig serum and demonstration in pig saliva and processing fluid from pig farms; demonstration on SARS-CoV-2 shown earlier in this proposal; demonstration of the detection and accuracy limits with use of e. coli indicating test quality on par or better that RT-PCR run in parallel under analogous conditions.

The early identification of infection can benefit the patient. The direct tracking of spatio-temporal distribution of the virus can lead to customized protective actions (hygiene, distancing, selective suspension of public services, selective quarantines) preventing emergence of superspreading centers which fuel epidemics, reducing the spread of the virus, and limiting its debilitating economic impact.