Hey! Isabelle and Ashley here, a team driven by a passion for global health and bio-innovation. With Helio, we are on a mission to mitigate micronutrient (MN) deficiency in low-middle income countries (LMICs) through low-cost point of care (POC) screening systems.
Why we started Helio
Micronutrient deficiency, known as the “hidden hunger,” has been recognized as a global problem by hundreds of NGOs like the World Health Organization (WHO), UNICEF and CDC. Nearly 28 billion USD has been pledged to tackle malnutrition from the Bill & Melinda Gates Foundation and UNICEF in 2021 alone. Despite massive efforts to employ intervention programs in LMICs, their design and implementation remain a challenge due to the lack of population MN data. Without population MN data, it is difficult to:
Identify regions/countries where programs are most needed
Customize programs to maximize their efficacy
It is estimated over 75% of LMICs aren’t meeting the WHO’s recommendation for micronutrient data to be collected every 5 years.
Since 1980, only 55.8% of LMICs reported population data on vitamin A 8.4% on ferritin for iron, 15.2% for zinc, 5.8% for vitamin D, and only 5.1% for vitamin B12
Where we left off…
From our last newsletter, we chatted with 9 experts from NGOs (WHO, UNICEF, USAID, CDC, PATH, the Micronutrient Forum) on a low-cost POC biosensor and confirmed :
The lack of MN data is the primary barrier to why intervention programs are not being established where they are most needed. When there is no MN data, there is no evidence MN deficiency exists.
The root causes for the lack of data are the high costs and tediousness of storing/shipping blood samples overseas
We were also deciding on a micronutrient for the focus of our biosensor and in the midst of asking experts for their insights.
Where we are now
Choosing vitamin B12!
After much research and expert insight, we decided to proceed with building a biosensor to assess vitamin B12 status. Several researchers leading data collection initiatives at NGOs have suggested vitamin B12 as it is often overlooked and excluded from MN population surveys.
It is estimated that 70-80% of the population in certain areas may be B12 deficient and those who are vitamin B12 deficient are estimated to have a 3.8 point IQ variance in comparison to those who are sufficient. For every country that is able to eliminate vitamin B12 deficiency, we estimate 15.2% of economic growth (every 1 point of IQ gained = 4% of economic growth).
Choosing biomarkers
For the past two weeks, we have narrowed down to three functional B12 biomarkers for measuring vitamin B12 status: Serum holo-transcobalamin II (HoloTC), methylmalonic acid (MMA), and homocysteine (Hcy).
After presenting our idea to cluB12UK, an organization of nutritional scientists and healthcare professionals who specialize in vitamin B12 research (among various other micronutrients), we have made our decision to assess HoloTC. Elevated Hcy is unspecific to vitamin B12 deficiency, and MMA still remains a biomarker of great controversy with no authorized methods of assessment.
Delving into biosensor systems
To ensure compatibility with population assessment in LMICs, ideally, our biosensor :
Is a one-step procedure (more steps such as washing/incubating require a laboratory) capable of being conducted in small spaces
Is reusable or at most involving a replaceable component (e.g. a replaceable paper strip, a micro-fluidic chip)
Involves chemical reagents not prone to inactivity/denaturing in changing environments (e.g. temperature, exposure to sunlight)
Thus far, we are researching four specific systems within two broad biosensor categories: electrochemical and colorimetric. The components of the biosensor (e.g. recognition antibodies, aptamers) will be determined after further research into HoloTC.
Electrochemical
Electrochemical systems function by detecting the resulting electron transfer from a redox reaction. The way that this redox reaction occurs can be
Direct, between the analyte of interest and a bioreceptor (e.g. antibody, aptamer, DNA strand)
Indirect, which includes a biological label
Labelled systems (as shown below) are more common because there are few bioreceptors that can undergo redox reactions with the analyte of interest. However, labelled systems require washing between each step (i.e. while adding the sample/substrate or reporting the solution) and would require professional training to administer the test.
To avoid this challenge while taking advantage of labelled electrochemical systems, we discovered micro-fluidic chips. The entire system is automated, with human interaction only needed to pour the sample solution, reporter solution (containing the detection antibodies + enzymatic label), and enzyme-substrate through the inlets.
The solutions are mixed through the serpentine channels by capillary flow. Such chips can be built for under 0.01 USD each!
In the past, these micro-fluidic systems have been constructed for the labelled detection of malaria biomarkers.
Colorimetric
Colorimetric biosensors use chemical reactions between a highly-specific biorecognition element and the analyte of interest to produce a colour change in a solution.
The image below illustrates a colorimetric biosensor system using aptamers (short DNA strands) and gold nanoparticles (AuNPs). AuNPs are capable of appearing blue when they are in fixed positions close together. When the analyte of interest is introduced into a solution containing AuNPs, aptamers bind to the analyte, bringing AuNPs close together and fixing them causing the solution to appear blue.
In the past, AuNPs and aptamers have been used to detect ions, melamine and interleukin-6.
In our case, we will adopt this model to detect B12 biomarkers. Two aptamers will be designed - one to wrap around one side of the biomarker, and the other to wrap around the other. The analyte acts as a clip and pulls the nanoparticles close together and cause the solution to appear blue. The intensity of blue in the sample is correlated with the concentration of the analyte, and can be quantified via a smartphone scanner.
Other exciting news
Meeting with cluB12UK
We presented our biosensor idea to cluB12UK, an incredible group of researchers sharing knowledge and coordinating the research of vitamin B12 between scientists and healthcare professionals.
Applying to Future’s Fund
Future’s Fund is a philanthropic fund investing grants and funding to support ambitious projects that will support humanity in the long-run. We hope to hear back sometime in the next two weeks!
What’s up next
Ask experts working with biosensors and nano-fabrication for advice on a biosensor system that would be best suited for our project
Design the biosensor that will allow for specific and sensitive detection of HoloTC, now that we’ve decided to use HoloTC as our biomarker
Apply for funding from the Bill and Melinda Gates Foundation, where there is particular interest in low-cost instruments for micronutrient assessment
Advice, Resources and, Connecting
If you’d like to further discuss some of our topics or ideas, feel free to schedule a meeting with us or shoot us an email! Everything we mentioned is a more simplified version of the bigger picture. We would love to hear your thoughts.