To contain an outbreak successfully, societies need a rapid diagnostic response. Diagnostic tests, able to quickly adapt to new pathogens, can enable such a response. Current testing methods, such as PCR or antigen tests, do not meet the demand for rapidly adaptable, point-of-care diagnostics. Here, we present how we will develop Rapidemic to meet this demand.
Rapidemic uses a combination of methods to detect pathogen DNA, bringing significant advantages. While the techniques that make up Rapidemic are not new, the way we combine these techniques make Rapidemic an efficient and novel technology. The technology uses a unique method to couple the isothermal amplification reaction RPA to a DNAzyme-based readout. This brings several advantages. The kits do not require the expensive ingredients often used in RDTs, so they can be produced at a lower cost than many competitors’ kits. The low and constant temperature required for RPA alleviates the need for a heating element, making Rapidemic ideal for use-cases where no power is available, such as low-resource areas. As the detection is primer-based, it is possible to pre-produce and distribute the generic part of the kit before an outbreak and add pathogen-specific primers later. This makes the technology ideal for scaling up during an outbreak. Believing in Rapidemic’s inventivity and novelty, we have filed a national patent application for our project. To help future iGEM teams with patenting their inventions, we have documented our patenting journey in the iGEM Quick Guide to Patenting.
We have identified several key customer groups whose needs are not met by current testing methods, and who could benefit from Rapidemic’s advantages. These include government health care agencies, clinicians, nursing homes, school boards, employers, and consumers. We have already received signals from prominent potential clients, such as the Amsterdam University Medical Center, that our test could be valuable for hospitals to quickly determine which patients need to be treated in isolation.
We will focus on respiratory-borne RNA viruses because they have high pandemic potential and because screening is essential to prevent the spread of these viruses. Because influenza A outbreaks occur yearly, cause high mortality, and place a high burden on national health systems, we have chosen to focus on influenza A diagnostics as our first product. The kit will be valuable by allowing rapid diagnosis of influenza, allowing early administration of antiviral drugs, and improving health outcomes. On a broader scale, it will allow to quickly and economically screen large numbers of people for influenza during major outbreaks.
Our competitor analysis shows that currently marketed kits often cannot distinguish between influenza strains, and either require purchasing (expensive) equipment or have low accuracy. Currently used technologies such as PCR, antibody, and antigen-based tests all have different shortcomings. Rapidemic combines the strengths of these tests by being point-of-care, rapidly adaptable, inexpensive, and providing fast results.
We have created a roadmap for bringing Rapidemic to the market in the Netherlands as an influenza A diagnostic method. Our R&D roadmap includes additional laboratory research, prototyping the kit, validating it with end users, patenting, and obtaining legislative approval. The commercial roadmap includes obtaining funding, identifying customers, and establishing manufacturing and distribution. The total development is expected to take almost 4 years.
Using a SWOT analysis, we identified that our technology is promising and that the COVID-19 pandemic has increased demand for diagnostics, creating product-market fit. However, our development plans also contain risks, which we aim to minimize. These include a decrease in the demand for diagnostics after the COVID-19 pandemic ends, a competitor developing a superior technology, or failing to obtain the required sensitivity or specificity in our final kit.
In our stakeholder analysis, we list vital partners for further development. Among these are clinicians and other end users, Leiden University, and companies that design, commercialize, and produce RDTs. During our human practices, we interviewed over 25 relevant stakeholders, including RDT developers such as DCN Dx, Mondial Diagnostics, and Scope Biosciences. In the long-term, we aim to develop partnerships with NGOs to supply our kit to developing countries as explained on our implementation page.
One important partner is IDE Group, a company that designs and commercializes medical products and has previously helped bring an RDT for HIV to market. IDE Group has provided us with a letter of intent, where they state that they would like to support our project.
WE have identified multiple funding sources, including the Enterprise Leiden Fund and the Netherlands Organization for Scientific Research. Together, these could provide $380,000 for development. Aiming to obtain seed funding for our project, we are participating in a local competition called Gulliver, where we stand the chance to win approximately $12,000.
Our project’s long-term impact is to prevent future outbreaks from spinning out of control. By focusing on pathogens with high pandemic potentials - such as influenza, coronaviruses, and RSV - we could make sure we are prepared for an outbreak. Providing rapid testing where it is needed most - at hospitals, GPs, workplaces, and educational facilities - can help prevent the enormous societal and economical consequences of lockdowns and save countless lives. Furthermore, Rapidemic could provide diagnostics for (tropical) diseases in low-resource areas, where PCR diagnostics are often not available.
We are aware of the possible negative societal impacts of our product. Discarded Rapidemic kits can cause environmental pollution lacking waste disposal practices. We aim to tackle this negative externality by using biodegradable materials for the kit and setting up proper waste disposal agreements. Moreover, wealth inequality may make the kits unavailable for low-income economies. We strive towards overcoming the wealth gap by pricing the kit depending on the country’s income. Finally, if our kit would ever be marketed to consumers, we would have to be aware of potential rise in the false-negative results due to incorrect self-administration.
Rapidemic as a realistic solution
We have invented Rapidemic, a nucleic acid-based detection technology, to develop into a rapidly adaptable, accurate, and accessible diagnostic test for infectious diseases. To show that Rapidemic is a realistic solution to prevent an outbreak from turning into a pandemic, we provide answers to critical questions about the product’s feasibility and inventivity. We will discuss the key considerations making the product a realistic solution: Is robust and sensitive detection feasible with the technology? Are the production and distribution costs viable? How can we use the product’s scalability to adapt to the market’s demand? Why is the product inventive?
Global importance: how important is testing in outbreak control?
Airborne pathogens such as influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread from person to person through the air1. An infectious individual breathes out virus particles, which another person can inhale to get infected by the virus as well. Therefore, it is critical to isolate infectious individuals. While showing symptoms may serve as a cue for isolation, sometimes the infectious individuals do not develop disease symptoms at all, or only in a later stage of the infection2. Besides, symptoms are often not specific for only one disease. Therefore, testing is required for reliable diagnosis. Sensitive testing makes it possible to distinguish between healthy and infected individuals, enabling rapid self-isolation to prevent viral spread.
A rapid diagnostic response at the start of the outbreak is crucial for successful outbreak containment3,4. To enable such a rapid response, we must be prepared, by having diagnostic tests that can be quickly adapted to new or mutated pathogens. Moreover, efficient outbreak control requires frequent and sensitive testing3,4. Firstly, frequent testing is important as an individual may become infected soon after they are tested. By testing people regularly, it is possible to identify such individuals before they infect others. Secondly, sensitive testing is important to identify infectious individuals early on. Right after infection, the virus has not yet replicated to high copy numbers. A test with a low limit of detection, or lowest detectable viral load, is thus crucial for early diagnosis. Lastly, since existing tests with high sensitivity, such as PCR, require laboratory equipment and expertise, they may not be accessible in low-resource areas5,6. Altogether, there is an urgent need for quickly adaptable, accurate, and accessible testing.
Have a look at our interactive epidemiological model to see how important testing is for outbreak control!
Feasibility: what makes Rapidemic suitable for diagnostic responses to outbreaks?
As concluded in the previous paragraph, there is a need for quickly adaptable, accurate, and accessible testing. The Rapidemic technology addresses these aspects with its modular nature and its potential to be used as a point-of-care diagnostic tool.
The Rapidemic kit uses an isothermal amplification method called recombinase polymerase amplification (RPA). With this method, a specific nucleic acid sequence is amplified at a low and constant temperature7. Among isothermal amplification methods, RPA was found to be a promising method for point-of-care use due to its low reaction temperature (~ 30 to 42 °C) and relatively simple primer design7,8 (see Results page). In contrast, loop-mediated amplification (LAMP), for instance, works at 65 °C and requires four or six primers9. Moreover, Rapidemic combines RPA with a colorimetric output to enable detection by the naked eye within 50 minutes (see Proof of concept page). Altogether, the lack of specialized laboratory equipment for incubation and readout makes testing with Rapidemic possible in point-of-care settings.
Rapidemic’s sensitivity and specificity are expected to be similar to PCR, the golden standard of testing5,7. The detection limit of RPA can be as low as 10 copies10. Thus, in the early stage after infection when the viral RNA concentration is low, Rapidemic could still be able to detect the target sequence. The high specificity (low rate of false positives) of RPA originates from its specific set of primers; amplification cannot occur unless the target sequence-of-interest is present in the sample. In the development phase, the kit and its primers will be validated to obtain legislative approval, since the primer sequences are essential for the kit’s performance. In practice, the high sensitivity and specificity of Rapidemic mean that it is not necessary to repeat the test in a clinical laboratory after a positive result. Instead, the result can be used to immediately conclude whether the person is infected or not.
Rapidemic’s modularity is demonstrated in its ability to be adapted to detect any pathogen, as long as the amplification primers, sampling, and extraction steps are chosen correctly. In case the extraction method is similar for the new and the previous application, only the primers would have to be changed, making the test’s adaptation very simple and fast. For example, this would be highly useful for most respiratory RNA viruses, which are prone to mutate and for which various strains exist11,12.
Rapidemic tests will be easy and fast to administer (see Hardware page). Because of their colorimetric readout, the result will be easily interpretable. To improve accessibility to testing, we have designed the readout to be color-blind friendly. When commercialized, we expect our test kit to provide a result within one hour after sampling (see Proof of concept page). The short testing time and fast results will allow for frequent screening with a minimum delay and cost.
Viability: why is Rapidemic an affordable testing solution?
Our team incorporated affordability into the design of Rapidemic. Comparing its design to other test kits has shown that Rapidemic fares better in comparison to most competitors.
Testing is a viable economic solution for both companies and governments. For the former, it helps provide a safe working environment, in compliance with local epidemiology laws. The importance of testing was visible in September 2020, when the Dutch government announced that it would close down company offices in which COVID-19 infections spread for 2 weeks13. Evidently, this had an enormous impact on these companies. For governments, testing can prevent costs incurred by an uncontrolled outbreak. For example, the CDC estimated that the US health system will bear direct costs of 5.3 billion USD for every million people who seek treatment for COVID-1914.
The socio-economic consequences of outbreaks underline the importance of affordable testing. Keeping these in mind, our team incorporated affordability into the design of Rapidemic. A label-free method, Rapidemic circumvents the need for expensive ingredients often used in most RDTs, such as antibodies and colloidal gold15. Instead, Rapidemic’s detection is based on primers that serve a dual purpose: they detect and amplify a target nucleic acid sequence, while simultaneously creating a specific and short strand of DNA. This DNA sequence, also called a DNAzyme, has enzyme-like activity and acts as a reporter. The DNAzyme-based reporter eliminates the need for labeled probes or protein reporters. The dual-purpose of the primer thus reduces the number of ingredients that need to be added, lowering the production costs of the kit. Other reaction components are similar to routinely used amplification kits, such as polymerases, dNTPs, and amplification buffers.
The reagent costs of the Rapidemic technology are similar to those of commercial amplification kits (see Fig. 1 and Proof of concept page). Rapidemic’s reagents cost approximately $1.45 per reaction, and we expect to decrease these costs by optimizing our chemical reactions and by obtaining economies of scale during mass production.
Fig. 1 Costs per reaction of 20 µL of commercial RT-PCR, LAMP and RPA assays compared to our technology.
Scalability: Rapidemic can be implemented on a wide scale
Thanks to its modular design, Rapidemic is a solution that can be implemented on a wide scale, and which can quickly adapt to soaring demands during a pandemic.
First of all, Rapidemic kits could be pre-produced, stockpiled, and finished by local partners. One of the largest obstructions to large-scale testing during a pandemic is that test kit manufacturing companies cannot meet demand. This is because they start production after the outbreak occurs. Thanks to Rapidemic’s flexibility, generic test kits can be easily adapted to a specific pathogen. This high adaptability of our technology makes it possible to have enough kits stockpiled to meet demand. This capability is made possible by Rapidemic’s unique modular design; Rapidemic kits all have a standard platform and an additional disease-specific part including a set of primers. The standard platform will be pre-produced in a centralized location and distributed worldwide. By concentrating production on one site, the company will save on employee wages and maintenance costs, while making it easier to perform quality control.
Furthermore, the kits without primers could then be stored locally. When an outbreak occurs, local partners will produce the primer mixtures, add these to the test kits, and distribute them to final testing sites. Producing primers locally helps support local companies. Simultaneously, it reduces the probability that the demand for primers cannot be met, since each company producing primers only needs to meet the demand for its area. Finally, because the primers are produced locally, the delivery times to end users are minimized.
Inventivity: why has nobody ever done this before?
Our product is novel and inventive as its technology differs from existing detection systems with significant advantages. The Rapidemic technology uses a unique method to couple the isothermal amplification reaction RPA to a colorimetric readout. This readout is an oxidation reaction that is catalyzed by DNA enzymes (DNAzymes), short guanine-rich DNA sequences with an enzyme-like activity. This method is unique to the Rapidemic technology, as shown by analyzing the existing coupling methods. Li et al. (2019) have integrated the DNAzyme-based color reaction with isothermal exponential amplification reaction (EXPAR)16. However, their system severely limits the choice for a target sequence. Alternatively, Wang et al. (2019) have coupled the DNAzyme-based color reaction with asymmetric RPA17. The asymmetric RPA led to a large strand of bases adjacent to one end of the DNAzymes, possibly hampering their activity. Moreover, asymmetric amplification methods often suffer from low amplification efficiency and generation of non-specific products18,19. In contrast, with Rapidemic we employ the coupling of the DNAzyme-based color reaction with RPA through a third reaction: linear strand-displacement amplification (LSDA). In doing so, the drawbacks that come with asymmetric amplification are avoided and DNAzyme activity is maintained. The advantages over existing methods provide solid grounds for Rapidemic’s inventivity and novelty.
To qualify for patent eligibility, an invention must fulfill three criteria: it must be novel, inventive, and industrially applicable. Because we believe Rapidemic meets these criteria, we approached Dr. Frits Michiels, a patent attorney at the law firm V.O. (Vereenigde Octrooibureaux). Dr. Michiels saw value in our project, agreed that our invention was patentable, and decided to support us. He helped prepare a national patent application, which was filed on October 6th, 2020.
This national application has multiple benefits. Firstly, it allows us to spend 12 months from the filing date to further develop the technology and prove that it works, before filing a more costly international patent application (PCT). Meanwhile, the date of the filing (the so-called priority date) is registered. This means that if anyone discloses a similar invention after this date, we will still be able to maintain exclusivity on our technology. Thus, a national patent application provides us the chance to develop IP with only limited investment.
Secondly, a national patent application makes it easier to attract investors and to convince partners to collaborate with us. If we would not obtain a patent for our technology, it could easily be implemented by a larger competitor with more resources. This would greatly reduce the value of the start-up to investors. By protecting our IP, we will be able to maintain exclusive rights to our technology. This makes the company more attractive to investors and commercial partners, making it easier to obtain funding and other resources.
We documented our journey towards a patent to make a comprehensible guide for future teams. This guide is available on the Contributions page.
(Non-)health care organizations and consumers can all benefit from Rapidemic in different ways, from the preventive screening of employees to improving patient care. The low cost, ease of use, fast test results, and ability to detect a disease in early stages makes Rapidemic valuable for multiple groups of customers.
How does Rapidemic overcome shortcomings of current diagnostic methods and add value to the market?
Currently, diagnostic tests for RNA viruses can be categorized into three main types: nucleic acid amplification tests, antigen-based tests, and antibody tests. Table 1 presents the benefits and drawbacks of each type. Rapidemic is a unique product as it combines the advantages of nucleic-acid based tests with the benefits of antigen-based and antibody tests. We will provide an in-depth explanation below.
Table 1: Benefits and drawbacks of various types of tests.
|Type of test||What it detects||Benefits||Drawbacks|
|PCR-like tests||Pathogen RNA||Very high accuracy
Quantification of virus concentration possible
Low detection limit5,7
|Require costly equipment: thermocyclers
Require skilled operators5,7
|Antigen-based tests||Proteins of the virus||High specificity20
Short time to result21
|Require long development time22
Higher detection limit20,21,23,24
|Antibody tests||Human antibodies, created as a response to the virus||Point-of-care
Short time to result
|Do not detect in early stages of the disease
May detect even after an individual is not infectious21
Detects infection in the early stages of the disease
Both Rapidemic and PCR are examples of nucleic acid amplification tests. Such tests can detect a very small amount of specific nucleic acid sequence in the sample and amplify it. RPA and PCR can detect genetic material with a concentration as low as 10 copies per reaction5,10.
Meanwhile, existing antigen-based tests often give false-negative results in the early stages of the disease and have a low sensitivity (< 80%) compared to PCR24. False-negative results can be highly dangerous since they create a false sense of security which may result in inadvertent infections.
Antibody tests do not detect the presence of virus antigens but of human antibodies, which are formed during the human immune response to the pathogen. The antibodies may still be detected after the infectious period, and they can even remain in the blood for months after infection25,26. Therefore, antibody-based tests cannot determine whether a person is infected at the moment of testing, and can thus not indicate whether it is safe for someone to resume social interactions. This makes antibody tests unsuitable for screening and subsequent isolation. Altogether, Rapidemic is more suitable for screenings than existing RDTs due to its high sensitivity and ability to indicate whether a person is infectious.
Fast time to result
Rapidemic is expected to present the test result within one hour after sampling. This quick test time is a strong benefit over PCR. To use PCR, samples need to be transported from the sampling point to the laboratory, which requires a complex supply chain27. Because of this, PCR test results are often delivered days after the test has taken place. This makes PCR unsuitable for daily screenings, while such screenings are essential for society to function during an outbreak. For instance, rapid testing is useful for personnel of nursing homes before they go to work or for children before they go to school. Moreover, rapid testing is crucial for patients that need a rapid diagnosis before their treatment can start, since the type of treatment and antivirals often depend on the pathogen or its strain28.
Rapidemic is suitable for point-of-care use, which gives it a strong advantage over PCR. PCR requires large investments, including costly equipment, a laboratory setting, and trained personnel. It is a good method for testing in a hospital setting, but the investments make it almost impossible to carry out in poor, rural areas6. In contrast, Rapidemic does not require any costly laboratory equipment since all of the kit’s components work at a low and constant temperature and the result can be read with the naked eye. Therefore, Rapidemic can be carried out in remote areas without laboratory access or electricity to make testing accessible and affordable for everyone. Additionally, Rapidemic’s point-of-care character can also be employed in developed countries for preventive screening when there is no time or capacity to send a swab to a laboratory. For example, during an outbreak, hospitals can use Rapidemic at the door to assess which patients need to be treated in isolation.
Quickly adaptable to new pathogens
Because Rapidemic detects the pathogen’s nucleic acids using primers, the target of the test can be easily adapted by simply modifying the sequence of the primers. The primer set can be designed once the pathogen is sequenced. In practice, this means that testing can begin within days after an outbreak occurs.
Rapidemic can be used to respond to outbreaks of new diseases much faster than antigen-based tests or antibody tests. These tests require the validation of specific protein-protein interactions, which is less straightforward than nucleic acid interactions as with primers22. Therefore, the time to adapt the diagnostic kit to new pathogens is significantly longer. Although other nucleic acid-based tests exist, such as PCR tests, these tests’ inability to be used in a point-of-care setting hampers testing in low-resource areas or when the laboratory capacity is full. Rapidemic can thus be used to quickly respond to outbreaks, minimizing the effects of the pathogen on society.
To conclude, a summary of the comparison of Rapidemic with PCR, antigen, and antibody tests can be found in Table 2.
Table 2: Comparison of testing methods for respiratory RNA viruses.
|(RT-q)PCR||Antigen-based tests||Antibody tests||Rapidemic|
|Adaptable to new pathogens within days||Yes||No||No||Yes|
|Requires specialized training||Yes||No||No||No|
|Result within 1 hour after sampling||No||Yes||Yes||Yes|
|Detects infection in the early stages of the disease||Yes||No||No||Yes|
|O Favorable O Non-favorable|
Use-case scenarios and potential customers
Because of the aforementioned benefits of Rapidemic, our kit has many potential use cases. Since depending on a potential new pandemic is not a viable business plan, we plan to focus on outbreaks that occur at a smaller scale.
We identified influenza A as our first use case, as influenza viruses cause many problems in health care and break out on a yearly basis, with a high mutation rate. Current techniques often fall short when it comes to influenza diagnostics. Being able to quickly identify flu strains is vital for effective treatment and adequate quarantine measures, especially in light of frequent mutations28. Besides, many flu strains of the subtype H1N1 have already caused many deaths in the past during the 1918 Spanish flu and 2009 swine flu pandemics29. Being able to rapidly detect infected people during outbreaks can prevent its spread.
This year, we saw that influenza is not the only virus that can lead to a pandemic. Therefore, another use case that we envision for Rapidemic is to manage outbreaks caused by pathogens other than influenza. This includes pathogens with high pandemic potential from the family of respiratory-borne RNA viruses such as RSV and coronaviruses. This use case is made possible thanks to the adaptability of Rapidemic.
With these use cases in mind, we have identified potential customers of Rapidemic as seen in Table 3.
Table 3: an overview of our identified customer groups and their value propositions
|Customer group||Examples (example in brackets)||Value proposition|
|Organizations diagnosing patients||Hospitals (LUMC)||For organizations providing health care services, implementing Rapidemic for screening of potentially infected individuals would prevent the spread of disease and the affiliated negative consequences on the economy and or the health care sector. Furthermore, Rapidemic’s ease-of-use would help streamline their processes and provide a better patient experience. Also, source investigation and contact tracing could be made faster, easier and therefore, more effective.|
|General practitioners (Huisartsen Centrum Roodenburg)|
|Government health care departments (GGD Hollands Midden)|
|Organizations diagnosing employees or visitors||Nursing homes (Verpleeghuis Topaz Groenhoven)||For non-health care organizations, Rapidemic would allow screening employees and visitors on a regular basis, decreasing the probability of workplace outbreaks and allowing the organization to keep running.|
|Schools (Primary schools, high schools, and universities such as Leiden University)|
|Consumers||Anyone who feels the need for testing themselves.||For consumers, Rapidemic would allow them to quickly and accurately receive a diagnosis, without needing to visit a health practitioner. This could make it easier and faster to obtain a diagnosis, and provide a feeling of security when meeting others.|
Potential first customer during a new outbreak: hospitals (UMC Amsterdam)
During our human practices, we interviewed Dr. Robin van Houdt, who is part of the research unit of Medical Microbiology and Infection Control at the University Medical Centre of Amsterdam. Dr. Van Houdt told us that hospitals such as UMC Amsterdam would be interested in Rapidemic. Rapidemic’s low cost, ease of use, and fast test results could allow clinicians to identify patients who should be treated in isolation when visiting the hospital. According to Dr. Van Houdt, this could not only decrease costs and save time but also improve patient care. Furthermore, our kit could be used to prevent the spread of disease within the hospital itself. Current technologies cannot be used for this because they either take too long or are not sufficiently reliable (Table 2).
Potential first customers for influenza screening: nursing homes
Rapidemic could be used by any health care organization that is treating influenza patients. It is proven that it is important to determine the flu strain within 48 hours. After this period, the effectiveness of antiviral treatment decreases28. This is why lengthy laboratory tests, such as PCR are often too slow, especially because patients will not see a doctor at the start of the 48 hour period. Therefore, the ability of Rapidemic to immediately screen for the flu will potentially drastically improve patient care.
This is also why nursing homes, whose residents are highly vulnerable to the flu, can also benefit from Rapidemic during flu season. In 2019, 504.000 out of the 808.000 flu-related hospitalizations and 51.000 of the 61.000 flu-related deaths in the US were in individuals over the age of 6530. Outbreaks in nursing homes can cause many deaths. By testing their personnel and visitors during flu season, nursing homes can reduce the risk of an outbreak.
The diagnostics market is large, fragmented, and the major players differ per disease.
We have made an overview of currently available molecular and antigen-based diagnostic techniques for influenza detection, presented in Table 4 and Fig. 2. The analysis shows that our competition consists of molecular tests that require expensive equipment for reaction processing or readout, or antigen-based tests which lack sufficient sensitivity (< 80% compared to PCR) and cannot be quickly adapted to new pathogens.
Fig. 2 Gap in the market for point-of-care influenza tests. Rapidemic is expected to provide a unique combination of high sensitivity and the ability to provide results without the need for additional specialized equipment37,38.
The main competitor for our kit is Abbott’s ID NOW kit. Similarly to our kit, the ID NOW relies on an isothermal reaction, and can provide a result within 15 minutes. However, it requires a power source and is significantly more expensive than other tests. The customer must purchase a machine costing $4,50031, and each influenza test requires a cartridge costing approximately $30.70 (23,450 GBP for 1000 tests)32. In comparison, one Quidel QuickVue® Influenza A + B antigen-based test costs approximately $14.20 ($355 for 25 tests)33.
Besides the approved influenza kits, a number of LAMP-based kits have been developed for COVID-19 diagnostics (not shown in table). Because these kits could be used for other diseases (such as influenza), their manufacturers could become our competitors. However, the LAMP reaction occurs at a temperature of approximately 60-65 ˚C34. Therefore, LAMP kits require the user to purchase a heating block or must integrate heating in their device, which increases the costs and makes it more difficult to set up point-of-care testing. This gives our technology, which does not require additional heating, a significant advantage over LAMP.
Table 4: List of FDA-approved, CLIA-waived tests for detecting influenza A & B according to the CDC (as of August 2020)35, 36.
|Manufacturer||Product||Platform||Detects influenza A Subtypes?||Detects other respiratory viruses?||Approved Specimens||Test Time||Detection method|
|Abbott||ID NOW™ Influenza A & B 2||ID NOW™ Platform||No||No||NPS, NS direct, or NPS and NS in VTM||< 15 min||Molecular|
|BioFire, Inc. & BioMerieux||FilmArray® Respiratory Panel EZ||FilmArray 2.0 EZ||H1, H1pdm09, H3||Yes*||NPS in VTM||1-2 hr||Molecular|
|Cepheid||Xpert Xpress Flu||GeneXpert Xpress||No||No||NPS, NS in VTM||30-60 min||Molecular|
|Cepheid||Xpert Xpress Flu/RSV||GeneXpert Xpress||No||RSV||NPS, NS in VTM||30-60 min||Molecular|
|Mesa Biotech. Inc||Accula Flu A/Flu B||Accula Dock||No||No||NS direct||<30 min||Molecular|
|Roche Molecular Diagnostics||Cobas® Influenza A/B Assay||Cobas® Liat® Analyzer||No||No||NPS in VTM||<30 min||Molecular|
|Roche Molecular Diagnostics||Cobas ®Influenza A/B & RSV Assay||Cobas® Liat® Analyzer||No||RSV||NPS in VTM||<30 min||Molecular|
|Sekisui Diagnostics||Silaris Influenza A & B||Silaris Dock||No||No||NS direct||<30 min||Molecular|
|Abbott||Binax Now Influenza A & B Card 2||DIGIVALTM||No||No||NPS, NS direct||<15 min||Antigen|
|Becton Dickinson & Co||BD Veritor™ Flu A + B||BD Veritor Reader||No||No||NPS, NS direct||<15 min||Antigen|
|Becton Dickinson & Co.||BD Veritor™ Flu A + B||BD Veritor Plus Analyzer||No||No||NPS, NS direct||<15 min||Antigen|
|Quidel Corp.||Sofia® Influenza A + B FIA||Sofia FIA Analyzer||No||No||NS, NPS, NPA, NPW direct, NP, NPA, NPW in VTM||<15 min||Antigen|
|Quidel Corp.||Sofia® Influenza A + B FIA||Sofia 2 FIA Analyzer||No||No||NS, NPS, NPA, NPW direct, NP, NPA, NPW in VTM||<15 min||Antigen|
|Quidel Corp.||QuickVue® Influenza A + B||N/A||No||No||NPS, NS direct||<15 min||Antigen|
|Princeton BioMeditech Corp.||Multiple types||N/A||No||No||NS, NPS direct||<15 min||Antigen|
|*The FilmArray® Respiratory Panel EZ detects Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Parainfluenza Virus, Respiratory Syncytial Virus.|
To better understand what factors need to be taken into account during the development of Rapidemic, a SWOT analysis (Table 5) was conducted. The results indicate that the Rapidemic technology is promising. Additionally, right now is a good moment to develop diagnostics technology, due to the high market demand caused by the global pandemic.
We have also identified several risks. First, the demand for diagnostics may decrease after the pandemic. This could make it difficult to secure funding for further development. This risk can be mitigated by developing test kits for diseases with a high and stable demand for diagnostics, such as influenza. Second, if we lose Leiden University’s support, we would need to rent a laboratory and incur additional costs. Therefore, maintaining a good relationship with the university is crucial. Third, a competitor might develop a less expensive or more accurate kit, making our kit less attractive. We can mitigate this risk by focusing on our customers’ and end users’ demands during the kit development process, thereby making our product more attractive. Finally, our technology might fail during development, for example, due to low sensitivity or specificity. The impact of this risk can be minimized by using a minimal viable product (MVP) approach. In this approach, multiple iterations of inexpensive prototypes are used to validate whether the product meets the customers’ requirements. This avoids making high investments in early stages of development, where there is still a relatively high risk of failure. For example, costs will be decreased by first validating the chemical reactions using synthetic RNA to ensure appropriate sensitivity and specificity, before repeating the tests using (more costly to obtain) patient samples.
Table 5: SWOT analysis for Rapidemic development.
|- Our technology is easy to use, inexpensive, and does not require a laboratory or power source.
- Our technology can rapidly be adapted to new pathogens.
- We have filed a national patent application, which may help protect our IP in the future and increase value to investors.
|- Our technology still requires further development.
- Our team does not have the capacity to design and produce the test kits in-house.
- Obtaining certification and setting up production facilities for RDTs is highly expensive.
|- Due to the COVID-19 pandemic, governments and companies alike are looking to purchase novel diagnostics methods.
- Because market demand is high, it is currently easier to obtain financing for diagnostics methods than in the past.
- No kit similar to ours currently exists on the market.
|- After the COVID-19 pandemic, governments, businesses, and investors might become less interested in rapid testing and pandemic preparedness.
- Another company might develop a faster or less expensive testing method.
- If we lose the support from the university, we would need to rent an external laboratory.
Development plans and required skills and capabilities
The development and go-to-market of our kit are estimated to take approximately four years. Several crucial steps in the road to market include designing the kit, troubleshooting it, and obtaining regulatory approval. Furthermore, essential business processes will need to be set up, such as manufacturing and distribution. The development plan is presented in the form of a Gantt chart in figure 3.
Fig. 3: a Gantt chart of the development plan for Rapidemic.
To better understand how we can complete these steps, we have identified the most important skills and capabilities for each step. These are presented in Table 6. Furthermore, we have conducted a stakeholder analysis. The table also presents the most relevant stakeholders for each step in our development.
Table 6: the required resources and important stakeholders during the development of Rapidemic’s first product.
|Research & Development||Resources required||Stakeholders|
||Expertise on RDT kit design;
Prototyping facility with suitable tools
|RDT design companies, e.g. IDE Group;
Prototyping spaces, e.g. MakerSpace Leiden
Experienced molecular biologists
|Lab space owners, e.g. Leiden University or Biopartner
Team members of iGEM Team Leiden 2020
||User experience expertise;
|Clinical microbiology labs, e.g. LUMC;
|File an international patent application||Patenting expertise||Patent attorneys, e.g. Dr. Frits Michiels|
|Obtain legislative approval||Notified body||Notified body, e.g. BSI Group|
|Commercial development||Resources required||Stakeholders|
|Register company & trademark||Notary||Notary, e.g. Roes en de Vries Notarissen|
|Acquire funding||Organizations providing grants||Bio Science Park, Rabobank, NWO, Leiden University|
|Identify pilot customers||Business development and sales||Luris (Leiden University Technology Transfer Office)|
||Knowledge on RDT and primer;
RDT & primer manufacturing facilities
|RDT commercialization companies, e.g. IDE Group & DCN Dx;
RDT kit manufacturers, e.g. NanoRepro AG;
Oligonucleotide manufacturing companies, e.g. BaseClear
|Establish distribution channels||Supply chain expertise;
Warehouse management & logistics capacities
|Supply chain companies, e.g. DSV|
|Acquire customers in the Netherlands||Business development and sales||Newly hired team members for sales;
Potential customers, including:
Municipal health care services, e.g. GGD Hollands Midden;
Nursing home companies, e.g. Vitalis Groep;
School associations, e.g. Stedelijk Gymnasium Leiden;
As presented in Table 6, we will require support from stakeholders during the development and commercialization process. In early stages of development, we will require a laboratory, which we are currently accessing through Leiden University. Alternatively, these could be rented from Biopartner, a non-profit near our university that rents lab space to growing life science companies. Similarly, we will need a prototyping space such as MakerSpace Leiden to manufacture kit prototypes. IDE Group could also help us during later steps of the kit design, such as designing the kit packaging and finding manufacturing partners. Thereafter, we will need to obtain legislative approval, for which a notified body (such as BSI Group) would be required. After finalizing, we will need to file an international patent for the technology, for which we will require a patenting attorney (this will likely be our current attorney, Dr. Frits Michiels).
Customers and end users are some of the most important stakeholders in any business. The requirements set by various customers would need to be evaluated and incorporated early in the design process, followed by repeated user testing. This group of stakeholders includes governmental testing facilities for infectious diseases, GPs, employers, schools, nursing homes, and consumers with no previous experience in administering diagnostic tests. One valuable partner would be the Leiden University Medical Center since it could bring us into contact with a medical laboratory and with clinicians.
Various stakeholders would be required to achieve the project’s commercial goals. Luris, the technology transfer office of Leiden University, could be a valuable partner for conducting business development. For setting up manufacturing agreements, RDT commercialization companies (such as IDE Group and DCN Dx) and RDT manufacturing companies (such as NanoRepro AG) would need to be involved. Similarly, oligonucleotide manufacturing companies (such as BaseClear) would be needed to produce pathogen-specific primers. For setting up a supply chain and warehousing, a logistics partner certified for handling medical devices would be needed. One of the largest GMP-certified companies in this area is DSV. Furthermore, close contacts with RDT distributors (such as Bio-Connect Diagnostics) will be necessary to access their distribution networks. We also learned that partnerships with NGOs (such as the Bill & Melinda Gates Foundation) will be necessary to expand into developing countries, because of their established distribution networks.Stakeholders for obtaining funding are described below.
During our project, we interviewed various stakeholders relevant to the development of our kit. Among these were Mondial Diagnostics and Dianox, two companies that develop RDTs for neglected tropical diseases, as well as Scope Biosciences, an iGEM spin-off that is working on a CRISPR-based diagnostic method. We also spoke to DCN Dx, which supplies parts for lateral flow test development to other companies. The insights gained from these interviews are presented on our integrated human practices page.
Another very valuable partner for us will likely be IDE Group. IDE Group is a company that designs and commercializes RDTs. In the past, they have developed an HIV test with Atomo Diagnostics. IDE Group mentored us during the development process and has indicated that they believe that our project is valuable and would like to further support us in the future. Their expertise will be very useful during the development of our first product. IDE Group’s letter of intent can be found embedded below. This was published with permission from the IDE Group.
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The COVID-19 pandemic has had devastating consequences on society. Worldwide, over one million people died, and regular health care came to a halt to give way to COVID-19 patients41. However, the long-lasting lockdowns used to fight the spread of the virus also have serious consequences. The economy is collapsing, with over 100,000 small businesses closing in the US alone42. Social isolation and stress cause people to feel lonely43, and domestic abuse rates have spiked44.
Our project’s long-term impact is to prevent such consequences from occurring in future outbreaks. This could be achieved because Rapidemic will allow us to respond to outbreaks quicker. By focusing on pathogens with high pandemic potential - such as influenza, coronaviruses, and RSV - we could make sure we are prepared for an outbreak. Ensuring that testing is made available quickly can stop an outbreak before it becomes an epidemic, saving countless lives.
Because Rapidemic could allow testing to occur where it is needed most - at companies, schools, airports, and other frequently-visited places - it would be possible to prevent the spread of a disease without limiting people from going to school or work. This means that outbreaks would pose a far lower risk of shutting down society, reducing social and economic consequences. Fewer companies would go out of business, and the effects of an outbreak on daily lives would be few and short-noticed. And even if some services must be shut down, the fast rollout of testing will allow for quicker reopening.
Moreover, our human practices interviews taught us that developing countries have an even greater need for rapid diagnostics. Undeveloped, rural areas lack access to clinical laboratories, which prevents PCR from being used to diagnose individuals. People with symptoms of an infectious disease often cannot be tested. Meanwhile infected people are likely still to go to work if they do not have a test result because they strongly rely on their income.
By implementing Rapidemic in developing countries, we could provide a method for diagnosing individuals with a variety of infectious diseases. Besides being a rapid epidemic response tool, Rapidemic can fulfill the role that PCR has, in areas where laboratories are not available. Implementing Rapidemic will allow people who previously did not have access to diagnostics to receive faster and more accurate diagnoses, allowing them to be treated in earlier stages of disease, resulting in better health outcomes.
We have also thought about the potential negative impacts of our technology. The waste stream resulting from our RDT kits could cause negative impacts. Our HP research taught us that waste from medical products is a major problem in developing countries. Instead of being disposed of properly, medical waste is sometimes placed in open-dump sites near hospitals. Scavengers search these sites, attempting to find items of value to resell. This creates a public health risk, because the scavengers may acquire infections from the waste45. Thus, setting up proper waste disposal agreements with customers is crucial. For instance, by integrating after-use collection systems of the kits or incineration.
Furthermore, the materials used in the kit could pollute the environment. While we learned from Zavin that hospital waste is usually incinerated in the Netherlands, this often does not occur in developing countries. In these circumstances, producing the kits from biodegradable materials (such as cellulosic materials46) could reduce the pollution caused by the kit. However, the biodegradability must not negatively impact the shelf life and performance of the kits.
Additionally, new medical technologies pose the risk of increasing inequality between rich and poor. If the price of our rapid diagnostic test is too high, there is a risk that it will be unaffordable to low-income customers. Therefore, we aim to price Rapidemic test kits depending on the income in the country. Kits will have a higher price in developed countries, which will subsidize sales in developing countries or to NGO’s.
Finally, if our kit is ever marketed to consumers, there is a risk that users introduce human error while self-administering the test. In our human practices, we learned that this introduction of human error could increase the chance of false-negative results and create a false sense of security, which would likely lead to unnecessary infections. If we choose to enter the direct-to-consumer diagnostics market, we must ensure that our tests are easy to use and interpret.
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