Aiden McCurley's Site

This week we continued making a workshop on Sickle Cell Disease for medical professionals in Sierra Leone. For now this meant that we worked on a slide deck and held a meeting with the team members who were traveling. In this meeting we reworked the order that the information was going to be presented in. Another upcoming event are Press Conferences and my team and I worked on that slide deck based on the feedback we received last week during a practice presentation.

On Tuesday afternoon, Professor Cheng and I met with the OraSure team to discuss our future plans for test strip optimization. Since the previous group of experiments was a success, we are ready to move forward. The first set of experiments done this summer were to make sure our bead conjugation protocol was effective and consistent. We did this using a far cheaper antibody to save money. We are now ready to move on to using the monoclonal anti-hemoglobin antibody that we plan on using when our assay is fully functional. For this we will repeat some of the experiments done with the cheap antibody, as some steps in the protocol may be slightly different between various antibodies.

The latter part of the week was spent largely at Mountaintop. We met with a group of high school students that were participating in an Entrepreneurship program at Lehigh. We spoke with them in great detail about all aspects of out project and about our thoughts on going to Lehigh. Following this we had an Innovator in Residence. He spoke about being a cultivator in a large company and slowly but surely making a change with great impact even without having a powerful position. Friday all the MTSE projects had Press Conferences. It seemed like our presentation and Q&A went well. Later that day our team had a meeting where we furthered our plans for fieldwork and beyond. One way our plans developed was by beginning to work on a video series on SCD that could be distributed via WhatsApp to healthcare workers or families who are in need. These could provide varying level of detail on important topics focused on the disease itself, its treatment, or diagnosis.

This past week we performed a few experiments and made big changes to our plan for fieldwork in Sierra Leone. The first experiment we performed was to optimize the concentration of antibodies that will be loaded onto the beads during the conjugation. We tested four different concentrations and had visual results for which worked the best. This allowed us to plan ahead for the next experiment with the best concentration now in the protocol. The second experiment compared the protocol we have been using for our bead conjugations with one that had extra washes. We were able to perform the conjugation and run test strips with the two different bead variants successfully at Lehigh, but we need to wait for OraSure to become available for us to run the particle analysis on them. We also performed our first column purification at Lehigh, something I had done at OraSure and was now teaching to the other fellows. This allows us to desalt our antibodies prior to the conjugation process.

On Monday my team met with Khanjan to discuss our plans for fieldwork. This prompted a pivot from another set of interviews leading to a paper to creating and presenting a workshop on SCD to various levels of healthcare professionals. We began immediately brainstorming and creating our slide deck for this as we hope to have the support of key players in Sierra Leone.

This week began very slowly, with Monday and Tuesday being spent entirely working on the computer. During this time I reviewed last week’s experiment procedures and results and made sure that we had protocols and visuals that would allow for reliable results and reproducibility.  I also updated the procedure for the the first bead conjugation that was performed on Wednesday.

On Wednesday I was able to perform the first bead conjugation of the summer. This process is likely the main source of failures for the project. So to combat this, I performed it at OraSure under the instruction and supervision of one of their experienced scientists. This allowed me to further learn the ins and outs of the procedure, as well as valuable techniques that may not be in the protocol, but will lead to better more consistent results. This experiment in particular was to determine the optimal pH for our conjugation to occur at using two differently pHed buffers. The experiment was successful. We ran test strips comparing the performance of the two differently conjugated beads and saw that there was a clear better option. This will allow us to move forward, tweaking other aspects of our protocol until we are able to reliably produce excellent results. These results felt like a huge step forward, we confirmed a successful conjugation and have the steps in place to further optimize that process.

During this procedure another possible experiment arose in conversation. OraSure encouraged us to find every aspect of the protocol that could be challenged and major places where our protocol differed from the manufacturer’s. One of the largest differences in the two protocols was a set of additional washes that may either help with bead performance or cause particle aggregation, rendering the beads less effective. Following this discussion, I confirmed that this was something my team would be interested in evaluating. Since it was I wrote the protocol that would allow us to evaluate this through performance on test strips coupled with particle analysis at OraSure.

Another goal of this week was to make it possible to recreate every aspect of experiments performed at OraSure in the HST, our home lab. We are able to do this by utilizing some equipment that has been present, but never used by our team before. This includes and incubator and nanodrop spectrophotometer. The latter requires us to learn how to properly use it. We did this by making various dilutions of BSA (a cheap, common protein) in DI Water and we used the nanodrop to prove that the dilutions were the concentrations that we expected. We were able to do this with under 2.5% error in four different concentrations of the solution. This led to us writing a protocol for other team members to use in the future because we plan to incorporate the nanodrop into many of our future experiments. Using the nanodrop will allow us to have certainty that we have the concentration of antibodies that we think we have.

This four day week included lots more work in the lab than previous ones. Some of which was set-up for experiments and some was starting those experiments. At Lehigh we prepared many buffers including those for the bead conjugation, the bead diluent, and fresh buffer for when we are ready to run test strips. During these procedures, I taught the process and locations of various reagents. This involved learning how to pH a solution and add the correct amounts of chemicals to the buffers. One random task that was also completed was making a detailed diagram of our device that would aid in explaining how it works to incoming team members or other people of interest.

Outside of the lab, preparations occurred for experiments through meetings with the teams, at Lehigh and OraSure. At OraSure we discussed what we planned to do in the upcoming few days. This included using columns to purify our antibody, using a spectrophotometer to confirm our antibody concentrations after purification, and staining previously striped test strips to confirm that there was suitable protein for testing our conjugations. Some other points of discussion were the results of our ongoing experiment at Lehigh to determine the void volume of our test strip’s components, the possible switch to a different antibody for the bead conjugation, and more analysis of what could be going wrong with our current protocols.

On Thursday I was able to begin working in the lab at OraSure where they taught me the process of purifying and confirming the concentration of an antibody using column purification and absorbance readings from the spectrophotometer. This was a success as we produced a suitable volume of antibody that was an appropriate concentration for our upcoming experiments. We also used staining to test if the previously striped test strips had appropriate amounts of antibody on them for future experiments, which they did. Overall a successful beginning to the set of more serious experiments for the summer.

Sorry for the image quality, canva to blog does not seem to transfer well

This week was host to many tasks that seem to lead up to future work. On one side of things, I began by finalizing the budget proposal for the summer, our budget typically consist mainly of expensive reagents (antibodies, latex nanoparticles, etc.) and this one was no different. These reagents will help us restock for the rest of the summer and the experiments we want to run. A second task was with my fellow fellows and the team members who are traveling to Sierra Leone in August. This was to help them develop their questionnaire for the study they hope to conduct during fieldwork and was a priority because IRB approval typically takes a few months to be finalized.

On the more experimental side of things and in the interest of having a working test strip I have been preparing for the weeks to come also. I have communicated with many of the companies that we purchase reagents from in order to clarify certain specifications and ensure that we have all the details we need to troubleshoot our conjugation protocol. One example would be asking about the pHs of certain buffers that come in a kit and are just labeled Reaction Buffer A and B, which provides no information about the difference between them. Even worse, the procedure says to use either A or B, a confusing point in the protocol that we now have clarity on. In the interest of setting up for future experiments, I met with a group of scientists at OraSure to help walk me through certain possible points of failure that could be troubleshooted. This led to my writing procedures for four experiments that will be done this summer, either at Lehigh with the other fellows or at OraSure. In order to prepare the other fellows for the experiments to come I gave a chalk talk on the chemistry and process of latex nanoparticle conjugation and other general procedures that are crucial to the team’s ability to troubleshoot going forward.

Below is the link to the visual my team made this week so that some of our more complicated procedures become easier to learn for newer team members!

https://www.canva.com/design/DAFlPWTpajQ/F6TznqtBgysQPHgD2KUQxg/edit?utm_content=DAFlPWTpajQ&utm_campaign=designshare&utm_medium=link2&utm_source=sharebutton

Although my first week as a Mountaintop Fellow this summer was filled with paperwork and procedures, I am eager to get to the real work I have in mind. I am on the SicklED team, which is working to create a lateral flow diagnostic device for Sickle Cell Disease that is effective and affordable in lower income settings such as Sierra Leone. I have spent the last year and a half working on this project and this will be my second summer as a Mountaintop Fellow. and we have seemed to hit a spot in the lab where we are unable to produce consistently reliable results. This summer will be different.

These past two semesters my team has developed a partnership with OraSure Technologies Inc. and now I am a hybrid fellow-intern with Mountaintop and OraSure. My aspirations for the Mountaintop side are to help the other two fellows (who are relatively new to the team) become comfortable with leading the venture forward in its technology and plan for fieldwork. It can be a challenge to jump into a project that has been around for years and certainly to plan for fieldwork when so much is unknown. On the OraSure side of things I hope to learn everything my team will need going forward to troubleshoot and finish the development of our diagnostic test strip. It feels like we have been in the home stretch of development for over a year and just cannot produce the results we want. With our new partner, I believe we will now have access to the expertise we need to finally have a product that allows us to take the next steps as a venture.

However, this week I had to undergo the onboarding process with OraSure, which involved a lot of reading. Some of which were interesting, and some of which were detailed procedures to operate and clean machines that I had never seen before. However, I am nearing the end of my document-based training and should start more hands-on activities next week. Until then, I feel like I have a lot I want to learn this summer and only a few months to do so.

While trying to develop a low-cost syringe for the developing world context, you (the designer) hit a crossroads. Constructing the syringe to auto-disable after a single use, an important safety feature, significantly adds to the cost of the design – making it potentially unaffordable for some hospitals and clinics. However, if you don’t add the safety feature, you are enabling the potential for the spread of disease. How do you as a designer proceed?

Step 1: Determine the facts in the situation – obtain all the unbiased facts possible. Clearly state the ethical issue. 

• Syringes with auto-disable feature increases cost of production
• The syringe is intended to be low-cost for developing world for hospitals and clinics that cannot afford the syringes otherwise
• Having auto-disable syringes decreases probability of diseases spreading
• An auto disable syringe contains internal safety mechanisms that make sure that after a syringe cannot be reused
• The ethical issue at hand is the decision of whether life saving potential from vaccination or the reduced spread of disease is more important.

Step 2: Define the Stakeholders – those with a vested interest in the outcome 

• Primary
  • Those being vaccinated
  • people working in healthcare
  • syringe designers
  • syringe manufacturers
• Secondary
  • Investors in the syringe
• Tertiary
  • other companies that produce similar produces
  • Distant partners

Step 3: Assess the motivations of the Stakeholders 

• Motivation of primary stakeholders
  • Those receiving a vaccine/treatment through this syringe are seeking healthcare services to protect themselves against potentially harmful diseases.
  • The healthcare workers at hospitals and clinics are looking to have healthcare devices in their hospitals and clinics that are reliable and safe for the patients they are treating.
  • The managers and owners of the company are paying attention to profit opportunities, as well as impact on the health of a developing world.
  • Manufacturers of the product are motivated by the profit opportunities of the device.
• Motivation of secondary stakeholders
  • Investors in the product are motivated by potential profit making.
  • Close family members are looking out for the health of their family members and motivated by the desire for their well being.
• Motivation of tertiary stakeholders
  • The motivations of other syringe manufacturers mainly arise from competition/potentially wanting to utilize the technology of the syringe.
  • Distant partners are most likely looking for profit / mutually beneficial growth as a team.

Step 4: Formulate (at least three) alternative solutions – based on information available, using basic ethical core values as guide

• Work on developing a new auto-disable feature that is lower in cost
  • Ethical Principle or code
    • Virtue based thinking: choosing to work towards the best possible outcome for the public in the long wrong
    • Ethically, the auto disable feature should be included because you should not knowingly use a device that might spread a harmful disease; you are knowingly putting the lives of others at risk.
  • Pros
    • Eventually, you can still create a syringe that has the auto disable feature; a safe and effective way to administer healthcare through the syringe.
  • Cons
    • It will take time, have to research and spend years creating a new product. This means that lives that potentially could be saved using the vaccine without the auto disable feature will be lost from the disease.
• Create training lessons on how to safely dispose of the syringe
  • Ethical Principle or code
    • Care-based thinking, building relationships
    • You should ethically use the auto disable feature since it can prevent the spread of disease, but since it would take years to develop a lower-cost device with the feature, you can create education programs for proper sanitary techniques in regard to using syringes that do not have the auto disable feature.
  • Pros
    • Syringes can still be affordable for use. Mitigation of harm due to training.
  • Cons
    • Takes time, costs money to teach and run education programs. Will need more investors/funding.
• Apply for additional funding from outside sources (NGOs, grants) to start the venture, then if certain countries have free healthcare initiatives the product can be absorbed into that.
  • Ethical Principle or code
    • Virtue-based thinking: you are choosing to ensure that the auto disable feature is used and that the public is benefited at the end of the road.
  • Pros
    • Will be able to have the product with the auto disable feature that is still affordable for developing countries.
  • Cons
    • Is not permanent, will need to continuously seek funding to continue utilizing the device.

Step 5: Seek additional assistance, as appropriate – engineering codes of ethics, previous cases, peers, reliance on personal experience, inner reflection  (2-3 resources) 

• A supply gap of more than 1 billion autodisable syringes could impact COVID-19 immunization efforts in 100 countries
• Examining unsafe injection practices associated with auto-disable (AD) syringes: a systematic review
• NSPE Code of Ethics for Engineers

Step 6: Select the best course of action – that which satisfies the highest core ethical values. Explain reasoning and justify. Discuss your stance vis-a-vis other approaches discussed in the class. 

I think the best course of action here is to just wait until more funding is available and the ideal product with the disabling feature is able to be produced  and distributed. This way the priorities of minimizing disease spread and maximizing immunization can still be upheld. This may take a little bit longer, but with a product with this sort of impact potential I do not think it would be too hard to get this funding. The first solution seems less feasible and like it  would take longer because it is essentially just make the technology better. This does not really solve the issue in a way that is reliable and is known to be possible. The second solution of training people to dispose of syringes leaves a lot to chance. Even if training sessions happen people may be able to get their hands on the syringes and disease may still spread.

Step 7: (If applicable) What are the implications of your solution on the venture. Explain the impact of your proposed solution on the venture’s technology, economic, social and environmental aspects

Economically, the venture would simply require more money and would rely on outside sources most likely to do so. This may be challenging, but I perceive it as being worthwhile in the long run. Socially this is better for the venture because the product put out has the features it needs to have the best impact on its targeted  groups of people.

1. What are the top three things you learned during your Impact Fellowship? Please elaborate.

  One thing that I learned and is a main focus of these fellowships is that in order to really have an impact, ventures need to be sustainable. Real change stems from organizations that have the ability to function continuously, in a sustainable way, and have the ability to expand. Another thing I learned was that I have the ability to start making a change now. Feeling like I could  begin using my love of science to have a chance to better other’s lives as a student is very empowering and one of the main things that draws me to continue working on my venture. A third is that seeing is better than learning in a classroom. Fieldwork this summer made the work of my project come to life and seem much more real and important than when it was in a meeting room or a lab. Specifically for my project, seeing people who have dealt with Sickle Cell Disease in some way and what they have endured was very eye-opening.

2. How did the Impact Fellowship facilitate your professional development? Please provide three examples.

One important skill developed by the impact fellowship program is public speaking ability. I feel like between the first and last presentation my team and I have become much more confident and more effective in presenting our venture. This could come in handy in future presentations as well as interviews when I need to make a case for why I matter as opposed to why our  venture matters. Another skill is being more aware of and able to understand the practices and values of other cultures. I specifically recall the discussion of sweatshops in the spring semester and how we as Americans may villainize them in all situations without understanding that they may have benefits for some groups in other parts of the world. This is applicable in all realms of life as in reality, very few people will share the same background as you and making an effort to see something from someone else’s perspective is valuable. The last professional skill is having experience in healthcare in other parts of the world. Being able to dive into the function of a vastly different healthcare system was extremely interesting and being able to compare it to the US’s was difficult but has its merit. This may be applicable as I hope to enter the world of medicine and may have an interest in attempting to improve it if I can. Seeing and studying healthcare that is completely different could help me to think outside the box in this area.

3. How did the Impact Fellowship help you grow personally? Please provide three examples.

This fellowship has forced me to really work in a group. Many times in classes the work can be easily split up and done as a few individuals rather than actually putting heads together and thinking as a team. For these fellowships the nature of the work makes it far more advantageous to really collaborate. Going off of this I have grown in being less stubborn and more willing to compromise when issues arise. This is important all year long, but much more so during fieldwork. The time in Sierra Leone is so limited and being argumentative generally will only reduce how productive your team will be and how much your venture will be able to accomplish following the trip. Finally, I have continued to hone my skills as a creative problem solver. This has come from situations during fieldwork and in the lab during device optimization. I think this matters a lot for my future because science is driven by creativity and pushing the limits of what is known.

– From the “Story Elements” framework slides, CHOOSE ONE of the frameworks given. Doesn’t matter which – choose the one that speaks to you more. Once you’ve chosen one slide, ignore the other one.

• 1. Attention-getter – make us listen
• 2. The Challenge – state or frame the problem as a world-level challenge.
• 3. The Journey – explain your methodology in an active, action-oriented way.
• 4. The Battle – describe how, with the help of your allies (partners), you have or will overcome the challenge.
• 5. The Change – state the solution / outcome / catharsis of this story.

– As a Project Team, construct a story about your project using the five story elements in the order in which they are given, #1 through #5. Each element should have one or two carefully constructed sentences. 

1- Sickle cell disease is a life threatening blood disorder that unfortunately is most prevalent in the countries that lack the resources to fight it. However, we have a tangible solution that offers hope.

2- As a team, the main issue we face is the high mortality rate of children in Sierra Leone; 50-90% of SCD-affected individuals in this region die before the age of 5 (NCBI). The wide range of this statistic clearly indicates the lack of testing that is occurring in this region. 

3- Our project’s idea for how to improve the lives of those with SCD is to develop a diagnostic device that is affordable, available, and accurate. This plus a system to test newborns shortly following birth and connecting those who have SCD to treatment and other resources.

4- With the help of our global partnerships, the implementation and mass distribution of our point-of-care sickle cell diagnostic test strip for early diagnosis could significantly increase the life expectancy of SCD-affected individuals. 

5- Our team aims to have every hospital in Sierra Leone supplied with our test strip to test newborn babies for sickle cell disease, so that those positive for SCD can take early action treatment to manage the severity of the symptoms and reduce the child mortality rate. 

TEN takeaways / lessons learned / things to do differently next time

1. Include more specifics about the distribution process and how it will be adopted into the Sierra Leone healthcare system – both in regards to the malaria test and other possible tests available.
2. Discuss risk/contamination/quality control of the test strips during travel and how we will adjust our test strips for in-country use. Along with this, mention temperature controls and how we plan to adjust this as we continue to optimize our device. 
3. Should include more specifics on the malaria test strip and how it helps us implement our device – in specific regards to private and public clinics. 
4. Address the regulatory approvals needed by mentioning Creative Inquiry’s experience with getting a similar product (Ukweli) on the market.
5. Should speak about how we plan to teach the operation of the device by emphasizing its simplicity.
6. Emphasize more on the recent conferences we have attended and awards we have received.
7. Edit and enhance our business model and the financial side of our venture to make it more of a reality.
8. Elaborate on potential manufacturing models and plans with numbers attached to prices as well as metrics of success. 
9. Aim to have more consistent results in working prototype in lab by next presentations that are quantified with specific numbers. 
10. Elaborate on what sets our device apart from other sickle cell diagnostic devices on the current market to enhance why our device would better be implemented compared to others.