The S.A.M.D.S.T.

Developing a Simple, Self-administered, Inexpensive prenatal Screening Test for Down Syndrome for the billions of people in the Developing World.

Developing One Drop Lateral Flow (LFA) Test Kits similar in concept to the latest Covid 19 test kits to determine the chance a fetus has Down Syndrome. The LFA would measure hCG (human Chorionic Gonadotropin) and PAPP-A (Pregnancy Associated Plasma Protein) levels in the blood. hCG is a biochemical marker that initially indicates whether a woman is pregnant or not and later the risk for Down Syndrome. PAPP-A is another biochemical marker that identifies fetuses with an abnormal number of chromosomes. Low PAPP-A levels are associated with Down Syndrome. 

During the first week of Pregnancy hCG rises rapidly. Thereafter, the concentration of hCG begins to fall. Increased total hCG levels are associated with an increased risk for Down Syndrome. 

Given that hCG and PAPP-A levels change over time, two tests need to be taken over a several week period and tracked in our mobile app.

The quantitative level of hCG and PAPP-A currently can only be determined by a vial of blood taken from the pregnant woman’s arm, kept cool in a lab, and then analyzed in a lab by skilled technicians. This severely limits the number of people who can test for Down Syndrome in the Developing World.

Inadequate access to prenatal Down Syndrome testing is a widespread issue across the Developing World like Sub Saharan Africa, Haiti, Central America and South Asia that affects several billion people. Virtually every option is out of reach for many people living in these areas. Down Syndrome is the most common chromosomal disorder and the most common cause of mental and physical disability with around 1 in 700 babies being born with it. It occurs when a person has three copies of Chromosome 21 rather than the normal two - one from the mother and one from the father. 50% of these babies are born with a congenital heart defect. Despite this, Down Syndrome is the least funded major genetic condition by our National Institutes of Health (approximately $50 million dollars per year out of a $50 billion dollar annual budget) and receives little to no funding in the Developing World.

Hopefuly our accessible and inexpensive S.A.M.D.S.T. will invigorate funding and research towards Down Syndrome, with an end goal of total prevention and cure.

Our target population is the annual 400 million “Soon To Be Parents'' in the Developing World who want to be informed of their unborn child’s health conditions, especially if they have Down Syndrome but do not have access to a blood testing laboratory, skilled technicians or the money required to do testing. In talking with dozens of our target population members, we have seen that almost everyone has access to a phone with a camera. Our solution is a Lateral Flow Assay that requires no technician (self-administered), costs pennies, and is accessible via a mobile phone. With this, parents have access to a previously unavailable test. If they receive a result that indicates Down Syndrome, the parents can then go to an area with medical facilities as there is a high likelihood the child may be born with a life threatening disability.

As a team, we have conducted hours of interviews, spent time in these areas like rural Peru, and have seen the extreme lack of access to things like electricity, internet, and healthcare. One constant that we have seen is that nearly everyone has access to a phone either through themselves or a relative. This is what moved us towards a mobile app. 

As part of our non profit, which began in the summer of 2016, we have had many fundraisers for Down Syndrome children, and have integrated water therapy, gardening, and pottery into their daily lives for over 6 years. 

We began thinking about biological markers for the past 6 months. We have contacted MGH, Harvard Catalyst, and several obstetricians at Brigham & Women’s Hospital to partner with. They are waiting for us to receive either a grant or funding before they will proceed.  

We have also contacted Quest diagnostics and LabCorp, global leaders in medical tests and assays.

In addition, we have reached out to LFA manufactures like IVD Research, DCNDX, and Abingdon Health.

hCG and PAPP-A are accurate markers for Down Syndrome when both tested quantitatively and used together along with maternal age.

We have also found that a self administered LFA is the most cost effective and accessible way of testing for hCG and PAPP-A. This is because of the demand for Covid 19 testing, companies have learned how to mass produce LFAs exponentially with a major decrease in cost. For our LFA, we are in the process of evaluating different combinations of conjugate pads, nitrocellulose and wick sample pads.

To make the test quantitative, something must analyze the LFA result. We found that a free app is the most accessible way of doing this since, through our in-country research we have found that almost everyone in our target population has access to a phone or a relative with a phone. Our team created an algorithm that can take an image of an LFA test result and find the test/ control lines and the max saturation value of the test line, and based on the value, give a concentration of hCG. This is because there is a linear relationship between the log of hCG concentration and max saturation value.

 Our solution is both a new technology - Lateral Flow Test that measures both hCG & PAPP-A and a new application of an existing technology that would test both qualitatively and quantitatively for hCG and PAPP-A levels respectively in a droplet of the pregnant woman's blood using a self-administered finger stick. The drop of blood would be put in a Two-Track Lateral Flow Test similar in concept to the latest COVID-19 Two-Track Lateral Flow Test Kits (that measure IgM and IgG). Currently there is no LFA that reads for both hCG and PAPP-A.

       In addition, we are developing a new app in house that reads this data, records it and analyzes to give the patient a risk for Down Syndrome. As of now, the algorithm reads a photo of the test and gives a concentration of the biochemical markers, but this is only for ideal photo conditions, with higher end cameras. We believe a more advanced AI is required for use in the Developing World, where the camera quality and conditions might be less than ideal. 

Since our device is in the concept phase, it has not been used yet. We estimate 50,000 devices can be made and shipped in a year. This number is based on the estimated cost to test the design, make the devices in bulk, and ship them. This means 25,000 people (2 devices per person) can use our S.A.M.D.S.T. within the first year.

When we get feedback from these users, which we estimate will be after a year, we will make adjustments for our next group, 125,000 people. This process continuously repeats, with our end goal being that within 10 years, our target population will be 1 billion people, roughly everyone who needs it.

Our impact goals for the next year are: 

1. Establish what criteria of PAPP-A and hCG combined determine the likelihood that the fetus has Down Syndrome

2. Determine the correct combination of conjugate pad, nitrocellulose and sample wick pad for our LFA

3. Create a prototype LFA that reads for hCG and PAPP-A with a self drawn fingerstick of blood

4. Develop and test the app/software on our prototype

5. Get feedback from potential users on the device/app (about 50 people)

6. Secure a deal with manufactures

7. Make, publish and share our app

8. Send out devices to our contacts, users (max 25,000)

9. Get feedback from this longer list of users

10. Prepare for a larger rollout next year (250,000 devices)

Our solution is in line with the UN Sustainable development goal in these ways:

• Increasing reproductive, maternal and child health care access

• Lessen healthcare inequality, equitable access (our LFA is self-administered, inexpensive and widely accessible)

• Ease the burden on healthcare workers, since our device does not require technicians or a blood lab because it is self-administered

• Increases the data collection on a group of people who would not otherwise be in the pool due to the cost, lack of trained technicians, and a blood lab facility

With the end goal of total access to prenatal Down Syndrome testing, we believe the steps towards that are:

• The device works from a tech standpoint, it can accurately read hCG and PAPP-A

• The app works from a tech standpoint, it can read all reasonable test photos and convert them into an associated risk.

• Both the device and app work from a user standpoint, in that users find them easy and simple to use. 

• An overall accuracy of at least 80% for the test, this is in accordance with standard blood tests for Down Syndrome.

• Widespread access to the device/app, remove all financial, accessibility, cultural, etc. barriers.

We need experts in PAPP-A/hCG lab testing, and experts in Lateral Flow Assay design. This will make the prototype and testing phase require less external research. 

We need an in-house person with expertise in AI who will help to develop a more advanced algorithm. 

Also an expert in Down Syndrome research, for example,  germline maintenance chromosome inheritance during meiosis.  This would help us verify our research. 

Other barriers are:

Arranging for manufacturers to make our initial devices.

Finding a manufacturer to mass produce them.

Having a larger potential user base in order to expedite the testing process.

Distribution of the initial 50,000 devices.

Establishing a connection with international and impactful groups like WHO and regional health organizations will expedite the adoption of our S.A.M.D.S.T. throughout the developing world.

Tancrede Roy of Boston, Massachusetts is the founder of the Tancrede Swim Challenge for Down Syndrome which began six years ago. To date, the Challenge has raised more than $50,000. Tancrede became the youngest person to swim the Straits of Messina from Sicily to the Italian Mainland. He arranged with the Italian Coast Guard to form a grassroots initiative that supported local children with Down Syndrome. The Tancrede Swim Challenge is now in its sixth year, with many swimmers, increased press coverage and fundraising. The Swim Challenge has pioneered the use of water therapy to treat Down Syndrome and is now investigating biological markers that can be determined by a one drop Two-Track Lateral Flow Test to evaluate if a fetus has Down Syndrome.

Since the people that we are trying to serve do not have access to a blood lab or skilled technicians or often not even electricity, our solution has to be simple, self-administered and very inexpensive. Tancrede is a first generation native French speaker from his Mother’s side with an interest in landlocked West African countries that speak French, specifically the Republic of Niger (GDP per capita $510) and the Republic of Mali (GDP per capita $891).  

John Paul Anderson is a Sophomore at UMass Amherst majoring in Physics and has worked extensively in Developing World health problems and has his own non-profit, Amautas (Amautas were noble teachers in Inca). His group was formed when John Paul’s mother explained how Peru (her native country) has a large discrepancy of technology use in its rural regions. John Paul has extended family in Peru, which fast tracked the outreaching process and created a reliable data loop. Amautas aims to close the technology gap in rural schools by teaching teachers how to best use the technology already accessible.

We have contacted MGH, Harvard Catalyst, and several obstetricians at Brigham & Women’s Hospital to partner with.

We have also contacted Quest diagnostics and LabCorp, global leaders in medical tests and assays.

In addition, we have reached out to LFA manufactures - IVD Research, DCNDX, and Abingdon Health.

They are waiting for us to receive either a grant or funding before they will proceed.

Our S.A.M.D.S.T. makes the screening of Down Syndrome dramatically more accessible, easier and only costs pennies. This takes a lot of the burden off mothers throughout the Developing World, who would otherwise not have access to Down Syndrome testing. The Pozen Prize will greatly increase the speed at which we have a shippable device. We need money for the creation and distribution of said devices, and any money towards this would be greatly appreciated.