eLAMP: Accurate and on-line COVID-19 diagnostic in saliva in 3 minutes

We will validate and deploy a reliable and ultrafast (i.e., 3 minutes), method for the COVID-19 diagnostic from saliva samples that can be used at home (for self-diagnostic) and in every work-place, and (b) develop the hardware, software, and analytics needed to enable the real-time analysis of all generated data.

Professor Mario Moisés Alvarez and Assistant Professor Grissel Trujillo-de Santiago, leaders of the Alvarez Trujillo-Lab at Tecnológico de Monterrey, México. 

At present, more than 2.3 million people have been diagnosed with COVID-19 in México, and the disease has killed more than 200,000 citizens, making it the most lethal infectious disease in a century. COVID-19 has exhibit the severe limitations in our capacities to respond to epidemic emergencies and has made clear that we must expand and strengthen the portfolio of available tools for effective diagnostics of infectious diseases both now and in the future.

The retro-transcriptase quantitative polymerase chain reaction (RT-qPCR) is currently the gold standard methodology for COVID-19 detection. Despite its unquestionable accuracy and robustness, qPCR-based methods lack of portability, depend on centralized facilities, need for technical expertise to conduct the testing, and imply  high infrastructural and operative costs. 

Due to all these limitations, RT-qPCR cannot be used massively in a cost-effective way to determine who is infected in a work place, at the entrance of an event, in a University classroom. We need robust, portable, cost-effective solutions that enable a safer comeback to our activities by quickly and reliably detecting even asymptomatic subjects. These solutions should allow fast diagnostic and localization of infected subjects (ideally in real time) to enable rapid decision making  based on this information.

Our solution serves individuals (i.e., by providing means of reliable, portable, and cost-effective diagnostics of COVID-19; extensible to other infectious disease). Also, our solutions serves the common well-being of the community by (a) enabling a more frequent and simpler testing of individuals and the detection of cases (inclusively asymptomatic) and (b) by providing a strategy for frequent and fast testing at any office, any workplace, any school, and even every home. 

The design of an interface capable of collecting online all the data from all the curves of amplification of all users of this testing device will allow us to elevate the impact of eLAMP. The network of data that we will collect using this new technology will enable the easier identification of zones of high incidence or high risk. That can not be easily done (at least in Mexico) using data derived from RT-PCR. 

The data collected in practically real time from all tests conducted using eLAMP will also serve the needs of decision makers. Much faster response will be possible to epidemic onsets in particular locations (any school or working place) by monitoring the number and trends of positives over time. 

This project will deliver several public goods.

In a first peer-reviewed publication we will describe eLAMP and present the data collected from the analysis of artificial saliva samples (proof-of-principle paper. A second paper will demonstrate that eLAMP is a portable and deployable system and that self-diagnostics is feasible using eLAMP. A third peer-reviewed paper will present the results from the pilot implementation of this technology in our University or any other education institution. We will show that this new diagnostic technology enables the rapid response of an organization in terms of cost-efficiently and rapidly detect infected people among the community to avoid epidemic onsets. 

During pandemic COVID-19 we have seen that the implementation of widespread diagnostics and selective quarantine can effectively buffer epidemic curves. Korea, Germany and other European countries have set the example in this regard. Numerous research papers have described how opportune widespread diagnose is key to contain pandemic events. We recently published a paper that quantifies the effect of different diagnostic intensities in containing local onsets of COVID-19 (Alvarez, M. M., González-González, E. (2021). Modeling COVID-19 epidemics in an Excel spreadsheet to enable first-hand accurate predictions of the pandemic evolution in urban areas. Scientific reports, 11(1), 1-12.). Our simulations clearly show that opportune and widespread diagnostic is highly effective. The effectivity of the ongoing worldwide vaccination programs will be highly enhanced if they are combined with aggressive diagnostic programs. (https://www.medrxiv.org/conten...).

Our solution will be of great value to our society because it enable both faster and accurate of every individual. In addition, our technology is portable and easily deployable. Also, we use saliva to detect SARS-CoV-2 which is much less intrusive than using nasal or pharyngeal samples (the current standard). Currently we do not have a technology that combines this attributes to respond to this and future pandemics. 

We believe that our solution has reached a TRL of 4. We have demonstrated that we can discriminate between saliva samples added or not added with synthetic SARS-CoV-2 genetic material. 

The next step for us is demonstrating that eLAMP also works well in the context of testing of real saliva samples from people infected or not infected with SARS-CoV-2. We must establish the sensitivity and specificity of eLAMP versus RT-qPCR in a clinical setting with at least 100 samples (30% should be possitive samples according to our plan). This will allow us to submitt our results to the Instituto de Referencia Epidemiológica (INDRE) and later to COFEPRIS for commercial approval in México. In parallel, we plan to conduct a pilot study in México, in the context of a University Campus or a medium-large company (most probably in Campus Monterrey at Tecnologico de Monterrey) to demonstrate that this solution can be really implemented for extended time periods and lowers the probability of epidemic onsets. 

We expect to run a similar effort in USA. In partnership with Aim Brands, we plan to commercialize this solution in USA in multiple organizations. 

We have mainly evaluated our progress in terms of the performance of the prototypes that we have produced. Sensibility (ability to correctly identify positives) and Specificity (ability to correctly identify negatives) are the two main indicators used to evaluate the accuracy of a diagnostic tool. The comparison is made against a reference method (i.e., for real samples the current accepted gold standard is RT-PCR). The third indicator that has been followed during development is time to get a result.

Our first prototype exhibited good sensibility (95%) but not equally good selectivity (aprox. 85%). A second version of LAMP that derived from our research is being piloted by Aim Brands in USA. Using this pre-commercial method we have observed very good sensibilities (95%) and improved selectivity (aprox. 92 %). Time to get results with our current system is 40 minutes. Our preliminary data based on synthetic saliva samples suggests that eLAMP exhibits sensibilities and specificities near 100% in less than 5 minutes. We expect to see a similar scenario in real saliva samples. 

As implementation in the community begins, the number of tests conducted (people diagnosed) and the number of organizations adopting this solution will become equally important indicators of success. 

Yes there are some important barriers to overcome for implementation in Mexico. This barriers are related to regulatory affairs. 

Regulatory matters in Mexico will be the main obstacle to overcame for an eventual commercialization of our solution in Mexico. 

The Mexican government has openly declared "not to  believe" on the need of intensifying diagnostics as a strategy to contain COVID-19 in México. As a results of this lack of "interest" in diagnostics for COVID-19, Mexico is one of the countries with the lowest level of RT-PCR testing per capita. 

In addition, the regulatory authority in México (Comisión Federal para la Protección contra Riesgos Sanitarios; COFEPRIS) has not approved yet any kit o of reagents or device for COVID-19 testing in saliva. Therefore, we will have to convince with very solid data and extraordinary negotiation skills on the need of expanding the portafolio of COVID-19 diagnostic tools and include saliva testing with our device as an alternative. 

We see more favorable scenarios for implementation in USA and possibly in other Latin American countries (.e.g., Colombia, Paraguay, or Chile).

Tecnológico de Monterrey , Monterrey México.

Tecnológico de Monterrey, a nonprofit organization, is the largest private university of México. Tec de Monterrey has more than 25 campi across México. Our research group, the Alvarez-Trujillo Lab, is based in the main Campus in Monterrey, N.L. México. 

We believe that this is a great opportunity to get international funding to evolve our solution (which has proven to be difficult here in Mexico) and greatly accelerate development and implementation at scale. 

In addition, we see the Trinity Challenge as a wonderful window to showcase what we are doing and seek for more collaborators and partners to scael this up. 

We have recently signed an agreement of collaborative research with Aim Brands, Co (Arkansa, USA) (https://aimbrands.com/). Aim Brands became interested in our developments in COVID-19 diagnostics and we have established a productive working relationship. Aim Brand is now piloting in USA the use of one of our primer sets for LAMP identification, in combination with the concept of using a miniPCR thermocycler, for Point of Care SARS-CoV-2 under the Brand Assura Screen. 

We want to extend our collaboration with Aim Brands in the context for testing and eventually commercializing eLAMP. 

We are extremely interested in partnering with Google. To be able to feed and analyze online (in real time) all information collected from people diagnosed with eLAMP will be extraordinarily powerful. 

In addition, we are truly interested in partnering with Amazon. Interestingly, most of the research that we have done during this pandemic year was done with components purchased through Amazon.com.mx and Amazon.com . We have been using Amazon as a distributor for our research products since our postdoctoral days at MIT and we firmelly believe in the democratization of research and the enabling power of companies such as Amazon to do so.