Periodic Reporting for period 2 - A-Patch (Autonomous Patch for Real-Time Detection of Infectious Disease)
Reporting period: 2020-07-01 to 2022-06-30
Tuberculosis 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. Nevertheless, many existing diagnostic tests are slow, have low sensitivity and specificity, and at times are expensive or complex. In A-Patch project, we aim to overcome these obstacles by integrating micro- and nano-technologies into an autonomous wearable system to detect disease markers directly from the skin for an effective triage test. TB-specific volatile organic compounds (VOCs) can be detected from the skin headspace by sensitive nanomaterial-based chemical sensors integrated in the patch. VOCs deviation from a healthy pattern may indicate on TB infection or high infection risk. The sensory area includes a fully flexible sensor array intended for short and single use. The system development focused on two tracks towards a low-cost, disposable electronics platform using flexible multi-functional, thin-film oxide transistors for wireless sensors. Sensors’ responses are recorded and transferred in a secured wireless connection to the application and server. Sensors’ signals are processed and statistical pattern recognition methods are applied to decipher the array's response. A developed algorithm is ascertaining the similarity level of the VOCs pattern array responses to either "TB suspected" or "Healthy" known patterns fed into the algorithm. A recommendation is then sent to the health care provider. Data analysis is done locally with the app/patch reader and at high-level computation at the server. Performance indicators include comparison of the obtained algorithm with WHO guidelines for a TB triage test. Server establishment, with interfacing to FIND’s and WHO’s TB management tools, will serve as the final demonstration that shows how the A-Patch result, can be mobilized by clinical systems. The development and verification of A-Patch is in full alignment with Responsible Research and Innovation (RRI) approach and involves user engagement, in addition to compliance with ethical guidelines. Besides the research and technological advances, the A-Patch project fosters European competitive ecosystems for the design and commercialization of innovative smart systems. As A-Patch is a sensing platform, its success can be a launch-pad for diagnosis of other diseases. The project delivered a final flexible reader demo and a hybrid patch combining thin-film printed electronics. A preliminary DFA algorithm was established based on the clinical validation trials preformed in Latvia, due to covid-19, number of clinical volunteers was low and thus results have statistical limits. Nevertheless, result achieved were promising. The results gave 100% specificity, above WHO threshold, and 69% sensitivity in training set but 100% in “test” set.
The main focus of the A-Patch project, was to define the device’s requirements and specs, to produce the sensory part and electronics to enable the screening of active TB by a skin patch. The project planed and advanced in parallel developing tracks towards a low-cost, disposable electronic platform for the patch using flexible multi-functional thin-film wireless sensors. Two tracks were achieved. First track prototype was used for validation in a clinical study presenting promising results, due to covid-19 pandemic (Force Majeure) enrollment in hospitals was hampered. Briefly:
Establishment requirements and specification documents that include topics such as: intended use, reliability, stability, physical description, technical and connectivity requirements, performances, cost, power consumption, server specification, ethics, etc.
Development of ‘off-line’ methods for collection of skin headspace’s VOCs and collection of the samples in Riga, Latvia from: 1) symptomatic TB patients, 2) symptomatic non-TB patients and 3) asymptomatic non-TB volunteers.
Development of the components. Sensor array based on molecularly modified gold nanoparticles was fabricated and optimized. The synthesis and deposition parameters were optimized. Electrodes were miniaturized and on-chip array was planned, manufactured, and characterized. Exposure to various disease-related VOCs and storage conditions yielded insights on the reproducibility and on the sensors’ drift.
Sensor readout circuitry development within two tracks towards a fully flexible design: 1) Development of readout pcb based system for clinical trials; 2) Development of a RFID-powered high resolution hybrid patch.
Development of a safe ICT platform and an application development for capturing personal data and sensors’ records in the DMS.
Establishment of data protection plan.
Development of the patch that includes a bio-compatible spacer preventing direct contact between the sensors and the skin.
Development and wearability testing of an arm strap for clinical study.
First prototype clinical validation study done in Latvia on active TB and control.
Development of a final A-patch demonstrator based on thin electronics and NFC battery free connectivity.
Analysis of skin VOCs, a DFA-based algorithm established for classifying samples of TB and control volunteers based on A-Patch sensors’. Classification accuracy was 83% that is above the defined threshold for the project (80%).
Plan for mass production and commercialization was done to promote the A-Patch concept design for future potential application.
Exploitation and business plans were prepared to assess the project and future possibilities.
Dissemination activities, RRI workshops, questioners and surveys were lunched and initial conclusions were driven about wearability, usability and user engagement
Establishment of project’s website and social media accounts and their maintenance in order to provide updates both for the general population and experts.
Establishment requirements and specification documents that include topics such as: intended use, reliability, stability, physical description, technical and connectivity requirements, performances, cost, power consumption, server specification, ethics, etc.
Development of ‘off-line’ methods for collection of skin headspace’s VOCs and collection of the samples in Riga, Latvia from: 1) symptomatic TB patients, 2) symptomatic non-TB patients and 3) asymptomatic non-TB volunteers.
Development of the components. Sensor array based on molecularly modified gold nanoparticles was fabricated and optimized. The synthesis and deposition parameters were optimized. Electrodes were miniaturized and on-chip array was planned, manufactured, and characterized. Exposure to various disease-related VOCs and storage conditions yielded insights on the reproducibility and on the sensors’ drift.
Sensor readout circuitry development within two tracks towards a fully flexible design: 1) Development of readout pcb based system for clinical trials; 2) Development of a RFID-powered high resolution hybrid patch.
Development of a safe ICT platform and an application development for capturing personal data and sensors’ records in the DMS.
Establishment of data protection plan.
Development of the patch that includes a bio-compatible spacer preventing direct contact between the sensors and the skin.
Development and wearability testing of an arm strap for clinical study.
First prototype clinical validation study done in Latvia on active TB and control.
Development of a final A-patch demonstrator based on thin electronics and NFC battery free connectivity.
Analysis of skin VOCs, a DFA-based algorithm established for classifying samples of TB and control volunteers based on A-Patch sensors’. Classification accuracy was 83% that is above the defined threshold for the project (80%).
Plan for mass production and commercialization was done to promote the A-Patch concept design for future potential application.
Exploitation and business plans were prepared to assess the project and future possibilities.
Dissemination activities, RRI workshops, questioners and surveys were lunched and initial conclusions were driven about wearability, usability and user engagement
Establishment of project’s website and social media accounts and their maintenance in order to provide 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 a lost of ~12 billion USD from the global economy. Early detection is one of the largest challenges of disease management. Thus, WHO published guidelines for TB Target Product Profile in order to define the requirements of future tests that may be endorsed by them. 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 is designed 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 technical expertise; 2) simple and inexpensive to manufacture at industrial scale; 3) simple operation, rapid and automatic results interpretation by integrated software stored in the server for future access by medical authorities; 4) 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.