Affordable, Reliable TB Screening

TB has been killing over 4000 people each day. For over 30 years. The most widely used diagnostic microscopy based test (88 million worldwide, 10 million in India), has a sensitivity of ~50%, diagnosing TB patients almost on the basis of a coin toss. It costs 20 cents and is widely available. Highly accurate PCR based tests cost about 50 times per test, and are only available at 1/16th of the locations in the country.

We have developed a sample collection device, which when combined with existing microscopy, makes it over 90% accurate (sensitive) (demonstrated in a field study in Uganda). It is powered by a polymer that acts as a magnet for TB causing bacteria, reducing effort and errors by overworked microscopists by concentrating bacteria to one spot.

Our device, sustainably affordable to governments, can correctly diagnose over 1 million patients worldwide each year, over 300,000 in India. 

In 2018, Tuberculosis(TB) resulted in approximately 1.6 million deaths worldwide. The identification of Mycobacterium Tuberculosis (MTb) is essential in diagnosing TB. It is estimated that only 56% of all TB cases are bacteriologically confirmed, making underdiagnosis a major contributor to the ongoing TB transmission. 

India has the largest TB incidence in the world, and current diagnostic field is fragmented, with no clear effective solutions, including WHO-endorsed GeneXpert. The Government has laid out an ambitious target for eradicating TB by 2025. Part of the government’s strategy is testing all presumptive patients and Increasing the number of correctly diagnosed patients. However, despite investing in high accuracy NAAT based systems like GeneXpert, there are significant gaps pertaining to accessibility.

About 10 million Sputum Smear Microscopy Tests were done at about 16000 public sector centers in India in 2018. These tests cost less than a dollar, and are the most widely used diagnostic test, despite having a sensitivity of only about 50% on average. Variabilities in the way experienced versus new lab technicians conduct testing largely affect the sensitivity of the test.

We're solving the need for a sensitive low cost diagnostic test that makes use of existing widespread infrastructure, and is easily distributable.

Our product (MagnaSlide) was designed to work in the existing infrastructural and user workflows and concentrates TB mycobacteria to a small spot on the microscopy slide.

This has three advantages:

1. By isolating and concentrating bacteria into a small region on the slide, even low concentrations are easier to detect (reducing the limit of detection to 800 - 1200 CFU/mL). 
2. The lab technician performing the test spends less time looking for the bacteria on the slide and can be sure of their assessment.
3. It eliminates inconsistencies in skill levels of sample preparation by lab technicians e.g. selection of the right part of the sputum samples.

Our system maintains optical transparency while selectively binding to TB causing mycobacteria, to permit bacterial concentration and enhancement of diagnostic sensitivity. We have designed a vial that contains a polymer coating on the cap that captures mycobacteria when centrifuged.

Increasing the sensitivity of smear microscopy from the current 50% to 75% in India alone, would positively affect over 300,000 patients yearly. 

Preliminary clinical testing was conducted in Uganda in late 2015 to compare the technology with known SSM-negative, Gene Xpert-positive samples. The polymer-based system demonstrated higher sensitivity (92%) than current SSM (50%), comparable to Gene Xpert.

Beneficiary: TB patients in India that access public sector testing (which is the de-facto testing facilities that even non-major private sector resort to)

End User: Lab technicians in India at the District Microscopy Centers (DMCs) who do smear microscopy tests

Customer/Payer: Central and State government run programs

Lab technicians who're overburdened with testing spend minimum time and effort trying to correctly locate and diagnose TB

Governments in high TB incidence countries (typically LMICs), who're always low on budgets can provide reliable TB diagnostics, at point of care to all its citizens, at an economical cost

Patients who partake in the public health testing system, despite the strong stigma, and undergo testing, get correct results and timely treatment

We have interviewed over 100 stakeholders across the world about challenges at different levels in the fight against TB. These have included patients, clinicians across various levels of the care continuum, epidemiologists, public health specials, researchers, innovators, funders, lab technicians, stakeholders in public health departments and large medtech companies in the space. Some of them are still part of the group we get recurring feedback from, some of them are part of our larger advisory group.

TB is a silent epidemic, which kills over 1.5 million people every year. While the developed world is using increased high end testing to monitor Covid19, this is an unsustainable strategy for other countries around the world; Governments simply cannot bleed money for extended periods of time on every outbreak, and have to rely on low-cost diagnostics for screening, control and tracking of diseases.

We have initially focused on the Indian TB population since it has the highest incidence and government momentum, but the need for need for accurate, low cost (for governments) is ubiquitous, for both screening and monitoring.

We're using an existing base technology to piggyback on - this gives us many advantages - no new training needed, no new reporting metrics

It is widely available, and saves time for technicians so they'll love it.

primary care centers and microscopy centers already have centrifuges so no new equipment required.

Since our test is low cost, it is accessible even to private players - they have an incentive cus the government will give them money if they diagnose correctly - they cannot afford state of the art machines, so that is lost value for them

the polymer and most parts we use are super cheap and are already regularly used

Using our device on a large scale is sustainable for governments ( they dont have to depend on aids and subsidies from BMG, etc)

Our technology takes advantage of the existing infrastructure that supports the use of SSM at primary health centers by increasing the sensitivity of SSM by improving the sputum sample quality. Our slide-based system concentrates and isolates the MTb contained within a sputum sample into a small spot. Our product is based on a TB-capturing cationic polymer system, poly diallyldimethylammonium chloride (pDADMAC) previously shown to have affinity for MTb.

We're using pDADMAC that we've tuned to capture mybacteria at a very high efficiency and that can work with staining and microscopy systems currently used, without having to significantly change the workflow.

This works with a balance between hydrophobicity, charge interactions between the surface and mycolic acid layers of mycobacteria. 

Our current manuscript titled "Selective mycobacterial capture with ultraviolet poly-dimethyldiallyl chloride functionalized surfaces" is currently under review. It describes the results of benchtop testing of the core polymer technology using non-virulent strains of mycobacteria, as well as results of our field study in Uganda, where the performance of the polymer was compared against existing smear microscopy and Gene Xpert.

Our team has optimized the system (in novel ways) for selective capture as well as high capture rates in a variety of conditions encountered in use case scenarios in low resource settings. Further, we have also been able to tune the system to capture bacteria while maintaining its viability, something that has not been demonstrated, and lends the technology open to applications outside of Smear Microscopy. We are unique in focusing on sample quality that is an unexplored part of the diagnostic pathway of currently used tools.

Publications about the technology:

Albert et al. Feasibility of magnetic bead technology for concentration of mycobacteria in sputum prior to fluorescence microscopy. BMC infectious diseases 2011 

Liu et al. Increased case finding of tuberculosis from sputum and sputum deposits after magnetic bead concentration of mycobacteria. Journal of microbiological methods 2013; 

Wilson et al. Concentration of Mycobacterium tuberculosis from sputum using ligand-coated magnetic beads. Int J Tuberc Lung Dis 2010 

Mekonen et al. Factors which contributed for low quality sputum smears for the detection of acid fast bacilli (AFB) at selected health centers in Ethiopia: A quality control perspective. PLoS One. 2018 Jun 2013

Key Goals: 

1. Increasing throughput of existing TB diagnosis microscopy infrastructure including material supplies and personnel to increase correct diagnosis of presenting TB patients. Microscopy centers (and testing) is much closer to patients than centralized settings with PCR based tests. 

2. Increase in the number of bacteriologically confirmed cases (ie remove risk of false notification) 

3. Development of Magnaslide's production prototype for deployment at DMCs, minimizing production cost) 

Methodology: 

1. Reliable and fast testing of all presumptive TB patients presenting at primary clinic/DMC level. 

2. Encouragement of private sector labs (first and preferred point of care for over 50% cases) to purchase and use microscopy devices in order to access government incentive due to low setup and per test costs (not possible with Xpert and TrueNAAT) 

Technical Specifications: Target sensitivity for MagnaSlide is 90% (as found in pilot study in Uganda). The slide system works with existing microscopy infrastructure, and requires minimum training of personnel. Low cost of device allows testing cost to be Rs 60 per test (vs Rs 40 earlier) about 1/20th of cost of PCR based test. This allows for over-testing. High sensitivity removes false notifications. 

Indicators: 

1. Increased number of bacteriologically confirmed cases 

2. Increase in number of PTB case notification (We also anticipate use of highly sensitive microscopy as a tool for active case finding) 

3. Increase in number of TB tests done/year in India 

Impact 

1. Increased access to testing 

2. Lower community transmission 

3. Faster discovery of local outbreaks. 

4. Increased number of patients on ATT

Timeline In the first year of rollout, assuming distribution at 5000 centers, a 25% increase in bacteriologically confirmed cases, over 1,50,000 bacteriologically confirmed cases in the year. We anticipate that in year 3 (after a revised view of correctly diagnosed cases), the morbidity will show a decrease due to more aggressive testing.

Expertise and training Minimal new training required for current diagnostic pathways. In case active contact tracing is done, training for sample collection will be required.

During 2020, there will be no sales; Numbers reflect field study participants

*DMCs = District Microscopy Centers (where are products will be used) [part of national and state programs]

Our development, and sales strategy follow the decision making structure for products introduced in the public health sector in India:

Our primary goal over the next year is to get recommendation for the product from the ICMR and begin the regulatory process in India. Once approved by the ICMR, we can begin sales to state governments.

This has 3 parts part

(a) Completing development - We're rigorously testing our final prototypes for performance in real world scenarios and are in the process of IP filing.

(b) Demonstration through clinical studies - We have partners in place (with IRB approval) to help conduct a preliminary study to further refine our prototype, as well as a clinical study to demonstrate performance of the product

(C) putting production and protection in place - We're currently filing IP, and establishing partners in India for small scale and mid-scale manufacturing of the products during the testing and phase I sales.

By 2023, we expect to start expanding outside of India.

Our timeline over the next years is given below:

One major risk we face is the ministry’s unclear balance between the costs of molecular diagnostics that are being pushed in the Indian (and world) public health system and the efficacy of our device (sensitivity and specificity); While we are increasing the sensitivity of smear microscopy which, due to its outreach, will affect over 300,000 patients each year, it is unclear what performance criteria for the cost increase will be enough. With Molbio (a PCR based system being introduced last year) set to cost the government about USD 500 million over a 5-year period in comparison to about USD 75 million with our device, there is reasonable confidence that current pricing is sufficient. We’re working with influential organizations like the India Health Fund and Tata trusts, who bring together stakeholders from the WHO, the ICMR, the Central TB division and the StopTB partnership, to establish clear performance specs, before the design is frozen for the clinical study, and the price is frozen for government approval.

Another risk is that the our current funding runway lasts until Decemeber, We’re planning to apply to the BIRAC grant in India (Government of India’s BioTech incubation program that come with a USD 75,000 grant), use that to conduct clinical studies, file IP in India before approaching the ICMR for recommendation. 

Finally, we will be a class A device (similar to class I in the US), and have a regulatory expert on our advisory committee to advise and help us navigate regulatory pathway in India.

2 full time staff members (co-founders)

1 part time member (co-founder)

1 engineering intern

advisory board

Bonolo leads research and clinical testing, along with the management of the project, funding, partnerships and commercial design. Digvijay leads  technology development, industrial and manufacturing design, and strategy as well as sales and marketing for the Indian market for the company. Yukari Manabe, MD leads clinical partnerships and funding for the company. 

The team is supported by Soumyadipta Acharya, MD, MSE, PhD (involved in inventions, raising money and co-founding companies in the global health space for about 10 years), Hai - Quan Mao, PhD, (known for his work engineering novel nanomaterials for regenerative medicine and therapy delivery applications, has over 20 patents in the materials science space), Derek Armstrong, MPH (international lab coordinator at Johns Hopkins who is regularly part of TB diagnostic studies using all current methods in these markets), Dr. Nicole Parish, (Director of Mycobacteria research at Johns Hopkins), and Youseph Yazdi, MBA, and Aditya Polsani, who are working towards raising funding and creating an advisory board with further expertise in policy, operations, and sales. We are also being advised by Dr GN Singh (ex-Drug Controller General of India who also headed the medical regulatory body in India), Mr Rohit Kumar (Principal Health Secretary of State, Rajasthan), Ms Gillian Henker (CTO, SISU Global Health, a global health startup based in Baltimore) and Mr William Niland (CEO, RegelTec, previously CEO of Harpoon Medical and VapoTherm). The team will be formally bringing some of these members on board after incorporation of the USA entity later this year.

The team has 2 sets of partners:

1. The Johns Hopkins University ecosystem (with members from the Center for Bioengineering Innovation and Design, Whiting School of Engineering, School of Medicine and the Bloomberg School of Public Health) towards development and testing of the devices.

2. Partner organisations in India towards field and clinical studies (already set in place) for testing and demonstration of the efficacy of the device

(a) YR Gaitonde Centre for AIDS Research and Education, Chennai 

(b) Institute for Respiratory Diseases, Jaipur