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Autonomous Patch for Real-Time Detection of Infectious Disease

Periodic Reporting for period 1 - A-Patch (Autonomous Patch for Real-Time Detection of Infectious Disease)

Reporting period: 2019-01-01 to 2020-06-30

"Tuberculosis (TB) is a major health problem in the world. About one-third of the world population has latent TB with a lifetime risk of 5 to 10% of developing active TB. Despite advances diagnostics, millions of patients continue to receive an incomplete or delayed diagnosis, as the physical signs and symptoms of TB are non-specific. Nevertheless, many existing diagnostic tests are slow, have low sensitivity and/or specificity, and at times are too expensive or complex. In A-Patch project, we aim to overcome these obstacles by integrating heterogeneous micro- and nano-technologies into an autonomous wearable system to detect disease markers directly from the skin surface to serve as an effective triage test. TB-specific volatile organic compounds (VOCs) can be detected, within minutes, from the skin headspace by highly sensitive nanomaterial-based chemical sensors integrated into the patch. Deviation of the VOCs from a healthy pattern may indicate either TB infection or high infection risk. The sensory area includes a fully flexible sensor array and intended for a short and single use. The system development is focused on three tracks towards a low-cost, disposable electronics platform for the patch using flexible multi-functional, thin-film oxide transistors for wireless sensors. Sensors’ responses are recorded and transferred in a wireless and secure connection to the designated application and server. Sensors’ responsive resistance signals are processed and statistical pattern recognition methods are then applied in order to decipher and interpret the array's response. The developed algorithm is ascertaining the level of similarity of a certain responsive pattern of the array responses to either ""TB suspected"" or ""Healthy"" known patterns that were fed into the algorithm. A recommendation is obtained and sent to the health care provider. The data analysis is done both locally with the app/patch reader and at high-level computation at the server. One of the main key performance indicators will include comparison of the obtained algorithm with the WHO guidelines for a TB triage test: specificity >70% and sensitivity >90%. Server establishment, with interfacing activities to FIND’s and WHO’s TB management tools, will serve as the final demonstration to provide a working technology that shows how the A-Patch result and supporting test data, can be mobilized by clinical systems. The development and verification of A-Patch devices is in a full alignment with Responsible Research and Innovation (RRI) approach and involves user engagement from the planning phase until the final results, in addition to the compliance to ethical guidelines. Besides the research and technological advances, the A-Patch project assists fostering European competitive ecosystems for the design and commercialization of innovative miniaturized smart systems. As A-Patch is a sensing platform, its success can be a launch-pad for diagnosis and/or follow-up of other diseases, including COVID-19."
The main focus of the first half of the A-Patch project, was to define the device’s requirements and specifications, and production of the sensory part of the device that would enable the screening of pulmonary active TB by a skin patch. The project evolved according to the plan with one deviation, instead of a single track of the system development, the consortium has decided to plan and advance three parallel developing tracks towards a low-cost, disposable electronics platform for the patch using flexible multi-functional, thin-film oxide transistors for wireless sensors. The elaborated course of work is detailed in Part B. Briefly:
1 Establishment requirements definition and specification documents that include topics such as: intended use case scenarios, reliability and
stability, physical description, technical requirements, connectivity requirements, performances, cost, electrical power consumption, cloud
server specification, ethics and others.
2 Development of ‘off-line’ methods for collection of skin headspace’s VOCs and collection of the samples in Riga, Latvia from three groups: 1)
symptomatic TB patients, 2) symptomatic non-TB patients and 3) asymptomatic non-TB volunteers. The study design included 420
volunteers.
3 Development of the sensory components. Sensor array based on molecularly modified gold nanoparticles was fabricated and optimized. The
synthesis and deposition parameters were manipulated and optimized. Electrodes have been miniaturized and on-chip array was planned,
manufactured, and characterized. Exposure to various disease-related VOCs and storage conditions yielded valuable insights on the
reproducibility as well as on the sensor(s) drift.
4 Sensor readout circuitry development within three parallel tracks towards a fully flexible design: 1) Development of readout pcb based
system for clinical trials in 2020; 2) Investigation of TFT-MUX feasibility for clinical trials in 2021; and 3) Development of a RFID-powered high
resolution TFT-ADC.
5 Development of a safe ICT platform in addition to application development for capturing personal data and sensors’ records.
6 Establishment of data protection plan and its updates.
7 Development of sensory part of the patch that includes a bio-compatible spacer in order to prevent form a direct contact between the
sensors and the skin.
8 Development of an arm strap for the first clinical track and its wearability testing.
9 Dissemination activities, RRI workshops, questioners and surveys were lunched and initial conclusions were driven about wearability, usability
and user engagement
10 Establishment of project’s website and social media accounts and their maintenance in order to provide an updates both for the general
population and experts.
TB is the leading cause of death from a single infectious disease agent, worldwide. TB is curable and preventable; nevertheless, remains a major global public health challenge and according to the estimations, causes about 12 billion USD to disappear from the global economy. Early detection is one of the largest challenges of disease management. As a result, WHO published guidelines for TB Target Product Profile in order to define the requirements of the future tests that may be endorsed by the organization. The ideal triage test is highly sensitive, non-sputum, low-cost, rapid, easily operated and can be done at any site. In the A-Patch project, we address these by designing, developing, manufacturing, and clinically validating a sensing patch. The patch are designed to be for a single use and characterized by low-cost and low energy consumption. The patch will be connected wirelessly to a mobile application to display multi-functional properties. The proposed system has several advantages over the existing technologies: 1) triage testing can be performed anywhere, without the need for any technical expertise; 2) the simple and inexpensive enough to manufacture at industrial scale; 3) operation of the device will be simple, and the results would be interpreted rapidly and automatically by the integrated software and stored in the server for future access by the national and international medical authorities; 5) and 5) the design of the patch and the sampling protocol is user and operator oriented – in order to reduce the stigmatization that is associated with the disease and increase the compliance of the public to get tested.
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