Improving Sample Collection for Accurate TB Diagnosis: A Q&A with Sinapi Biomedical
By Kristen Weber, Institute for Global Health, Northwestern University
Despite being curable, tuberculosis (TB) kills about 1.4 million people worldwide each year, primarily in sub-Saharan Africa. The TB diagnosis relies heavily on sputum samples – mucus that comes up when you cough – of which both quantity and quality is of high importance. Therefore, patients that are unable to discharge the sputum properly, produce insufficient volume, or whose collection container leaks may have an inaccurate test result.
In response to these challenges, Sinapi Biomedical of Stellenbosch, South Africa have developed an improved sputum collection cup, which was designed to minimize the number of rejected samples caused by disadvantages brought on by current cups. The pilot project is supported by the Center for Innovation in Point-of-Care Technologies for HIV/AIDS at Northwestern (C-THAN), whose focus is to facilitate the development and commercializing a pipeline of point-of-care technologies critical for improved management of HIV/AIDS and its common fatal comorbidities, such as tuberculosis. C-THAN is funded by the National Institutes for Health – Fogarty International Center and the National Institute for Biomedical Imaging and Bioengineering (NIBIB).
In a Q&A with Nardus Koekemoer, a Research and Development Engineer with Sinapi Biomedical, we discussed the development of the sputum cup, the improvements to the overall testing process, as well as the challenges brought on by COVID-19.
Read my Q&A with Koekemoer below.
How does this sputum collection cup improve the overall testing process for those being tested for tuberculosis and COVID-19, both for the patient and the laboratory? How does this cup improve upon those used in the past?
For TB patients, the Sinapi Sputum Cup makes use of a few design features that make it easier for the patient or healthcare professional to see if sufficient sputum has been collected. This is accomplished by optimizing the inner volume of the cup to only contain enough capacity for 1-4 ml of sputum and a 2:1 ratio of added buffer liquid for a total volume of 15 ml.
A minimum of 1 ml of sputa is required to conduct a test and this is further highlighted by a “MIN” text marking next to the level indicator line, and also colored blue for easy reference. Subsequently, a “MAX” text marking is also added next to the 4 ml level indicator line to show the patient where to stop, allowing some available capacity to still add the buffer liquid. A viewing window between the MIN & MAX level indicator lines is also provided completely around the circumference of the cup to allow for easy viewing of the liquid level at any angle.
Sinapi has designed a leak free cup that requires minimal effort to close. The effort is reduced by allowing the lid to engage the thread on the cup at any location. Once engaged, even before turning into the closed position, the lid has aligned itself perfectly perpendicular to the cup, thus eliminating the risk of any misalignment. Furthermore, the threads, once engaged, cannot cross-thread or climb over each other. A leak free cup ensures that an untainted sputum sample arrives safely at the laboratory and can easily be extracted for testing.
Although the Sinapi Sputum Cup was not designed for COVID-19 testing, one of the key advantages of using the Sinapi Sputum cup is that it reduces the need for patient repeat visits due to their initial samples being rejected (at the laboratory level) not having adequate amounts of sputa for testing. This minimizes unnecessary visits to the clinics, reducing risk of exposure to COVID-19, as patients suffering from TB are likely more vulnerable to the more severe COVID-19 symptoms.
Throughout the development of the cup, what has been the most challenging aspect to overcome? What have you learned from these challenges?
A challenge associated with the development of the cup would be getting the design iterations completed more quickly.
The most valuable lesson from the design and development to date is the principle of Agile Project Management, where the idea is to get a sample/prototype (something physical) in the hands of the client/user as soon as possible and having them involved in the design and development throughout. Not just getting their input at the start and then only after finishing the design presenting a solution to them. This has helped speed up design iterations and has also strengthened partnerships established. We have found that the users feel a sense of ownership and thus provide quality feedback rather than just quantity.
Briefly describe the current status of the pilot project, and what the next steps entail.
In regards to technical development, Sinapi is currently doing further design upgrades to the Sputum Cup Lid sealing lip. One of the distinguishing features of the Sputum Cup is an easy to open and close lid (reducing effort required) that also ensures a leak free cup for transport between clinic and laboratory.
We are currently in contact with the University of Sciences, Techniques, and Technologies of Bamako, Mali to assist us in doing a clinical trial using the Sinapi Sputum Cup. We are currently discussing a clinical trial protocol. The trial will aim to show a reduction in rejection rates (i.e. number of cup samples rejected due to insufficient sputum sample found within the cup (which can be caused by leakage during transportation and processing) in comparison to the current standard of care provided.
In addition, we are waiting upon the National Health Laboratory Service (NHLS) to continue with a local clinical trial to be conducted in the Gauteng and Western Cape provinces of South Africa. We have received approval of our protocol in the Western Cape and are awaiting approval for the Gauteng province. Unfortunately, COVID-19 has hampered progress, diverting the priorities of the NHLS to relief efforts, but we are hopeful to resume very soon.
As for next steps, our main goal is to begin selling the current cup design to local users, such as laboratories, so that we can start to capture user-based feedback which will allow us to quickly improve upon various user inputs. We also hope to begin a formal clinical trial, locally or abroad, to start capturing the required clinical data on a formal basis.
How has the COVID-19 pandemic impacted your work, how can the cup help in COVID-19 sample collection and testing?
COVID-19 has drastically affected our timelines for product clinical evaluation. This was to be conducted through, as mentioned above, two local clinical trials under the guidance of the NHLS (Lesley Scott - Associate Professor in the Department of Molecular Medicine and Haematology at the University of the Witwatersrand and Grant Theron – Head of Clinical Mycobacteriology and Epidemiology (CLIME) Group at Stellenbosch University (SU)). Both trials have been put on hold as both the NHLS and SU are assisting with the relief efforts of COVID-19.
The sputum cup is ideally suited to collect and enclose adequate amounts of respiratory tract (lower and upper) sputa needed for COVID-19 testing. General guidelines require that 2-3 ml of sputa be collected in a sterile, leak proof, screw cap sputum collection container. The Sinapi Sputum Cup is a non-sterile product, but can easily be sterilized using Ethylene Oxide or Autoclaving at 120 °C.
How will the cup be used commercially?
The cup design is focused on assisting the patient in expectorating sufficient sputum into the cup, using the MIN & MAX markings on the cup to indicate sufficient volume. This will be done at point-of-care facilities. Once closed, the sputum cup will be transported to a laboratory where the sample sputum will then be extracted from the cup (after adding a buffer liquid) and injected into a uniquely designed GeneXpert® container for testing.
The main aims are to: 1) Make it easy for patients and laboratory technicians to visually determine the sputum level contained in the cup; 2) Make it safe to transport from clinic to laboratory; 3) Have sufficient added volume capacity to allow for a 2:1 buffer liquid to be added, and 4) An easy to open and close lid. Lastly, we are also looking to slightly modify the cup for urine sampling.