Periodic Reporting for period 3 - ELSAH (Electronic smart patch system for wireless monitoring of molecular biomarkers for healthcare and well-being)
Okres sprawozdawczy: 2022-04-01 do 2023-12-31
While currently available wearables rely on monitoring physiological parameters such as the heart rate, an in-depth analysis requires continuous quantification of molecular biomarkers, which naturally entails direct contact with the user’s biofluids. To that end, blood is generally regarded as the gold reference biofluid, but blood sampling is an invasive technique that is incompatible to the needs of wearables users. In ELSAH, we targeted minimally invasive sampling of the dermal interstitial fluid (ISF), which has been proven to be highly similar in biomarker composition to blood. In addition, the probing of ISF by microneedles has been validated as pain-free. By enabling molecular detection in the ISF, we realized a wearable that provides truly evidence-based support to healthy living. This leads to better health and well-being, which in turn can be expected to also cause a reduction in the prevalence of diseases of affluence like obesity, cardiovascular diseases, high blood pressure or type 2 diabetes.
The overall objective of ELSAH was to realize a flexible and integrated smart patch-based wearable sensor system (‘ELSAH-patch’) that quantifies several molecular biomarkers in parallel by minimally invasive microneedle-based sampling and electrochemical detection. The ELSAH-patch is fully self-sustained by integrating the microneedle biosensor with microchip, battery and electronics (interconnects and antenna structures), thereby enabling independent measurements and secure wireless data transmission to the user’s mobile phone. To demonstrate our ELSAH-patch, we chose the two biomarkers glucose and lactate, which are amongst the most established and prominent biomarkers to support a healthy lifestyle.
Two separate ELSAH-patch demonstrators were developed and evaluated in the project:
• A clinical study demonstrator (codename Graz) aligning with key medical device regulations and used for first-in-human trials. The developed components biosensor and microchip were integrated with commercial solutions for batteries (coin cells), antenna and interconnects (PCB technology).
• A technology demonstrator (codename Vienna), which integrated all the technology and scientific modules (including printed battery and printed electronics) into a functional non-clinical device evaluated in a laboratory environment.
The ELSAH project brought together eleven leading partners from five European countries, including three research institutions, three universities and five companies (two large companies and three SMEs).
The overall objective of ELSAH was to realize a flexible and integrated smart patch-based wearable sensor system (‘ELSAH-patch’) that quantifies several molecular biomarkers in parallel by minimally invasive microneedle-based sampling and electrochemical detection. The ELSAH-patch is fully self-sustained by integrating the microneedle biosensor with microchip, battery and electronics (interconnects and antenna structures), thereby enabling independent measurements and secure wireless data transmission to the user’s mobile phone. To demonstrate our ELSAH-patch, we chose the two biomarkers glucose and lactate, which are amongst the most established and prominent biomarkers to support a healthy lifestyle.
Two separate ELSAH-patch demonstrators were developed and evaluated in the project:
• A clinical study demonstrator (codename Graz) aligning with key medical device regulations and used for first-in-human trials. The developed components biosensor and microchip were integrated with commercial solutions for batteries (coin cells), antenna and interconnects (PCB technology).
• A technology demonstrator (codename Vienna), which integrated all the technology and scientific modules (including printed battery and printed electronics) into a functional non-clinical device evaluated in a laboratory environment.
The ELSAH project brought together eleven leading partners from five European countries, including three research institutions, three universities and five companies (two large companies and three SMEs).
The ELSAH project was structured around realising and validating three system generations of increasing complexity and integration level. Life cycle assessment was performed for all three generations.
Regarding the 3rd generation, following results were obtained:
• The ELSAH-patch demonstrator for clinical study was designed, assembled and successfully tested. All components were fabricated, and quality controlled with full traceability through the distributed manufacturing flow across multiple European locations. In-vivo measurements were performed successfully using the devices.
• The ELSAH-patch technology demonstrator was designed, assembled and evaluated in a laboratory environment. Successful in-vitro measurements of glucose and lactate were performed on the sensor interface and the measured data were transferred to the laptop or mobile phone using the integrated printed antennas. The upload of the measured data to the Lykon server infrastructure was successfully tested.
Regarding the single components of the ELSAH system, following results were obtained:
- Lactazyme. A novel enzyme was designed to address the unmet need of a robust technology for lactate detection. The technology has been protected by a patent application (WO2022258733) and is commercialized under the tradename LactaZyme®.
- Microneedle-based electrochemical biosensor. Polymeric microneedles of the target dimensions were manufactured from medical-grade polymeric materials. Platinum instead of gold (used in the 1st generation) was used for the electrodes to reduce the environmental impact of the patch. Enzymatic hydrogel-based microneedle biofunctionalisation by dispensing with automated systems was established. The sterilization process using e-beam resulted compatible with the biosensors and certified biocompatibility tests showed no issues for the use in human clinical studies.
- Microchip. A highly versatile microchip was designed, fabricated and integrated, which is capable of measuring multi-channel electrochemical signals, processing them, and transmitting the data to a mobile phone via an NFC interface and/or by means of the integrated UHF transceiver. Together with the microchip firmware also a software app for operating the patch was developed.
- Patch applicator. To ensure controlled penetration of the epidermis by the 3rd generation clinical study patch and to establish reproducible patch adherence, an applicator system was developed.
- Printed battery. Three generations of printed batteries supplying to the microchip the required voltage and current for the sensing application were developed.
- Antenna. Three generations of NFC and UHF antennas were developed and successfully characterized.
The exploitation strategy developed in ELSAH includes an exploitation project led and financed by the ELSAH partner Lykon. This exploitation project takes places after the end of the ELSAH main project and has the goal to ensure that the most is made of the opportunity to exploit the IP and results generated during ELSAH. Moreover, an Indication of Interest (IoI) to ensure activities after the project end was prepared and signed by the project partners. The major dissemination activities were publications and presentations at scientific and technical events. All peer-reviewed publications were published open-access.
Regarding the 3rd generation, following results were obtained:
• The ELSAH-patch demonstrator for clinical study was designed, assembled and successfully tested. All components were fabricated, and quality controlled with full traceability through the distributed manufacturing flow across multiple European locations. In-vivo measurements were performed successfully using the devices.
• The ELSAH-patch technology demonstrator was designed, assembled and evaluated in a laboratory environment. Successful in-vitro measurements of glucose and lactate were performed on the sensor interface and the measured data were transferred to the laptop or mobile phone using the integrated printed antennas. The upload of the measured data to the Lykon server infrastructure was successfully tested.
Regarding the single components of the ELSAH system, following results were obtained:
- Lactazyme. A novel enzyme was designed to address the unmet need of a robust technology for lactate detection. The technology has been protected by a patent application (WO2022258733) and is commercialized under the tradename LactaZyme®.
- Microneedle-based electrochemical biosensor. Polymeric microneedles of the target dimensions were manufactured from medical-grade polymeric materials. Platinum instead of gold (used in the 1st generation) was used for the electrodes to reduce the environmental impact of the patch. Enzymatic hydrogel-based microneedle biofunctionalisation by dispensing with automated systems was established. The sterilization process using e-beam resulted compatible with the biosensors and certified biocompatibility tests showed no issues for the use in human clinical studies.
- Microchip. A highly versatile microchip was designed, fabricated and integrated, which is capable of measuring multi-channel electrochemical signals, processing them, and transmitting the data to a mobile phone via an NFC interface and/or by means of the integrated UHF transceiver. Together with the microchip firmware also a software app for operating the patch was developed.
- Patch applicator. To ensure controlled penetration of the epidermis by the 3rd generation clinical study patch and to establish reproducible patch adherence, an applicator system was developed.
- Printed battery. Three generations of printed batteries supplying to the microchip the required voltage and current for the sensing application were developed.
- Antenna. Three generations of NFC and UHF antennas were developed and successfully characterized.
The exploitation strategy developed in ELSAH includes an exploitation project led and financed by the ELSAH partner Lykon. This exploitation project takes places after the end of the ELSAH main project and has the goal to ensure that the most is made of the opportunity to exploit the IP and results generated during ELSAH. Moreover, an Indication of Interest (IoI) to ensure activities after the project end was prepared and signed by the project partners. The major dissemination activities were publications and presentations at scientific and technical events. All peer-reviewed publications were published open-access.
Main results achieved beyond the state of the art are:
- Wearable microneedle-based smart patch for the continuous monitoring of glucose and lactate in the interstitial dermal fluid and the secure wireless transfer of the collected data to a smartphone.
- Microneedle-based electrochemical biosensor for the quantification of glucose and lactate in the interstitial fluid.
- Direct electron transfer (DET) enzymatic hydrogel-based microneedle biofunctionalisation by automated dispensing.
- LactaZyme®, a biosensor enzyme capable of direct electron transfer for high precision, continuous lactate detection.
- Highly comprehensive microchip for (bio)-sensing applications with integrated potentiostat, edge processing abilities, near field NFC communication (NFC) and wireless UHF interface.
- Printed battery and printed antennas complying with the required dimensional and electrical parameters.
The potential impacts are:
- Enhancement of the applicability and usability of wearables in the health and well-being sector, thereby opening up entirely new application areas (e.g. personalised medicine through closed-loop theranostics).
- The ELSAH-patch system can support self-care of chronic disease patients and of healthy individuals to prevent the onset of chronic diseases.
- The ELSAH-patch system can be of great societal benefit to hobby sport individuals as well as to athletes.
- Benefits to healthcare professionals include a reduced danger of infection by using a non-invasive measurement technique.
- Wearable microneedle-based smart patch for the continuous monitoring of glucose and lactate in the interstitial dermal fluid and the secure wireless transfer of the collected data to a smartphone.
- Microneedle-based electrochemical biosensor for the quantification of glucose and lactate in the interstitial fluid.
- Direct electron transfer (DET) enzymatic hydrogel-based microneedle biofunctionalisation by automated dispensing.
- LactaZyme®, a biosensor enzyme capable of direct electron transfer for high precision, continuous lactate detection.
- Highly comprehensive microchip for (bio)-sensing applications with integrated potentiostat, edge processing abilities, near field NFC communication (NFC) and wireless UHF interface.
- Printed battery and printed antennas complying with the required dimensional and electrical parameters.
The potential impacts are:
- Enhancement of the applicability and usability of wearables in the health and well-being sector, thereby opening up entirely new application areas (e.g. personalised medicine through closed-loop theranostics).
- The ELSAH-patch system can support self-care of chronic disease patients and of healthy individuals to prevent the onset of chronic diseases.
- The ELSAH-patch system can be of great societal benefit to hobby sport individuals as well as to athletes.
- Benefits to healthcare professionals include a reduced danger of infection by using a non-invasive measurement technique.