Final Report Summary - RESPOC (Fast, cost-effective, user-friendly point of care (POC) instrument for detection of respiratory pathogens, including Streptococcus pneumoniae)
Executive Summary:
Molecular techniques such as PCR (polymerase chain reaction) are becoming increasingly used for the detection of respiratory pathogens, due to their high accuracy and relatively fast turnaround time (hours). Their utilization can result in early and specific treatment, contribute to better patient outcomes and reduce length of hospital stay. However, implementation of rapid molecular diagnostics remains limited to large, centralised laboratories which can afford the requirements of dedicated PCR laboratory space, specialized personnel and costly equipment and consumables. Even in central laboratories, timely diagnosis may be undermined by delays during sample transport to the setting and batching practices oriented to save consumables. There is a need for a fast, cost-effective, user-friendly molecular diagnostic point-of-care (POC) instrument for near-patient use at small to medium size hospitals, and decentralized clinical laboratories. The RESPOC platform will be a novel solution designed to detect bacterial and viral respiratory pathogens in less than one hour. Based on the development of DNA extraction and DNA amplification methods integrated into a low-cost microfluidic lab-on-a-chip (LoC) consumable, the platform will deliver results automatically by insertion of the disposable LoC into a small footprint reading instrument. Initially it will identify the target respiratory pathogens Streptococcus pneumoniae (pneumococcus) and Bordetella pertussis. Pre-clinical validation and demonstration of the RESPOC instrument will be performed to ensure adequate diagnostic performance and usability.
Project Context and Objectives:
The World Health Organization recognizes infectious diseases as a major global health problem despite widespread prevention through vaccination, and the use of antibiotic therapy.
Two of the most prominent pathogens causing vaccine-preventable infections are Streptococcus pneumoniae (pneumococcus) and Bordetella pertussis.
The early diagnosis and prompt treatment of invasive pneumococcal disease (IPD) and pertussis is vital to prevent progression of illness to severe clinical manifestations such as complicated pneumonia, meningitis and sepsis. Additionally, early diagnosis also allows for improved surveillance and control of community and nosocomial outbreaks of highly contagious pertussis. Early detection and adequate treatment also enable a more cost-effective utilization of health care resources.
Molecular techniques such as PCR (polymerase chain reaction) are becoming increasingly used for the detection of respiratory pathogens, due to their high accuracy and relatively fast turnaround time (hours). Their utilization can result in early and specific treatment, contribute to better patient outcomes and reduce length of hospital stay. However, implementation of rapid molecular diagnostics remains limited to large, centralised laboratories which can afford the requirements of dedicated PCR laboratory space, specialized personnel and costly equipment and consumables. Even in central laboratories, timely diagnosis may be undermined by delays during sample transport to the setting and batching practices oriented to save consumables.
There is a need for a fast, cost-effective, user-friendly molecular diagnostic point-of-care (POC) instrument for near-patient use at small to medium size hospitals, and decentralized clinical laboratories. The RESPOC platform will be a novel solution designed to detect bacterial and viral respiratory pathogens in less than one hour. Based on the development of DNA extraction and DNA amplification methods integrated into a low-cost microfluidic lab-on-a-chip (LoC) consumable, the platform will deliver results automatically by insertion of the disposable LoC into a small footprint reading instrument. Initially it will identify the target respiratory pathogens Streptococcus pneumoniae (pneumococcus) and Bordetella pertussis.
The aim of the project is to develop a molecular analysis point-of-care (POC) diagnostic instrument which overcomes the limitations of the state of the art. The device will integrate and automatically perform detection of the target pathogens. It will enable sample collection and analysis in a time frame between 15 and 45 minutes.
To this end, the following tasks have been undertaken by the project RTDs (HSJD, HSG, ATEKNEA) under the leadership of the consortium SMEs:
• Design, develop and optimize, a sample collection protocol and an isothermal molecular assay for DNA extraction and amplification.
• Design and develop a low cost microfluidics cartridge that accepts direct biological samples from nasopharyngeal swabs (for B. pertussis) or blood (for pneumococcus) samples.
• Design and develop the complete POC instrument integrating all necessary elements for automation of the assay protocol and subsequent fluorescence detection.
• Integrate the above and perform a laboratory validation of the analytic characteristics of the assay and an in-field pre-clinical validation of its diagnostic characteristics and usability.
Project Results:
The RESPOC instrument integrates the following steps: sample introduction, optimized method for fast DNA extraction, selective DNA amplification by means of suitable isothermal methods and detection by optical fluorescence.
The consortium SMEs (NTL, JCB, SURESCREEN and PATHOFINDER) have entrusted the development of RESPOC to 3 high-profile European RTDs with complementary expertise: HSJD (molecular microbiology laboratory of tertiary-level hospital), HSG (microfluidics, lab-on-a-chip) and ATEKNEA (electromechanics, integration, software).
During the first 12 months of the project, some key milestones in the development of the RESPOC instrument were achieved. A survey prepared by the consortium members served as a means to assess the actual market demands of end users. In addition, extensive search on commercially available solutions allowed the consortium to identify the required features for the RESPOC instrument and to define the key specifications to be fulfilled.
Following the definition of specifications, each RTD made good progress in the tasks assigned to their respective field of expertise. The different elements that led to the final RESPOC instrument were fully defined. Tasks performed in parallel can be divided into 3 categories:
(i) Development and optimization of the NAAT assay, led by Hospital Sant Joan de Déu. An exhaustive review of the state of the art in amplification techniques was undertaken. The consortium selected LAMP as the NAAT for implementation in the cartridge. Different methods for DNA extraction, including innovative pulsed electric field technology, were tested to enhance DNA extraction. Sample collection protocols and transfer to the cartridge were defined. The work then focused in the development of the NAAT assay, including selection of the target sequences, primer design and testing and optimization of the assay protocols.
(ii) Design of the microfluidic cartridge (pre-storage of reagents, microfluidics layout, materials and interface with control/reading elements). HSG applied their experience on Lab-on-a-chip systems to the development of the RESPOC microfluidic cartridge. The design obeys the specifications yielded by the previous optimization of the assay in the lab, including reagent volumes, reagent storage, extraction and amplification temperatures, etc.
(iii) Development of instrument modules and software. Taking into account specifications and with the constant input from other active work packages, ATEKNEA designed the instrument architecture with the aim to provide the desired functionality in the most cost effective way. In addition, different commercial processor boards were evaluated and the most suitable solution was selected for integration in the RESPOC instrument.
Starting in M13, efforts were progressively focused on the development of the designed elements and the integration into the final RESPOC instrument, in order to provide a complete instrument for validation, which was performed in ATEKNEA facilities.
The development of a final design of the microfluidic layout of the LabCard was performed during the second period. and 92 + 46 LabCards were produced for validation purposes.
Considering the specifications and inputs from the WPs, the following modules were developed:
1) Power supply
2) Touch screen and processor board
3) Top rotor board
4) Cartridge boards
5) Main control board
6) Optical design
According to the specifications gathered in WP1, the fluorophore used to react with the respiratory pathogens is the FITC. This means that the excitation wavelength is approximately 490nm - 495nm and the emitted fluorescence is allocated at 520nm. The distance between wells is about 3.2mm and the well size is 4.8mm2. It has been taken into account that the maximum crosstalk between wells is less than 1%.
The excitation light is projected into the mirror at the cardholder, and from the mirror to the wells. The emitted fluorescence is caught by the photodiodes. Afterwards those signals must be conditioned electronically and processed by the microcontroller allocated at the main control board, however another PCB was developed for this purpose.
Three detectors were used to verify the cross talk: one located at the spatial filter and one located at each photodiode. The wells were artificially switched on and off and the power measured.
Furthermore, the motor (7) was developed. According to the movements and positioning that are necessary for reading the optical measurement a servo drive and a servo motor has been chosen.
The motor has been also changed owing to the load has been increased practically in 400g. The stipulated weight at the beginning was 820g. This is due to the increase of the CardHolder and the addition of 2 batteries.
These models have been tested and then implemented in the laboratory scale prototype. This has been necessary to ensure the correct performance of the fluidic with the cartridges in vertical position and also to check the correct operation of all PCBs and the communication between them.Then with feedbacks obtained with the laboratory scale, the final instrument housing was designed to integrate all components required.
In addition to this, the development of the instrument software has been carried out. The graphical user interface acts via the touch screen. This software will also enable communication between the instrument and outside systems via USB or Ethernet, to enable update of instrument software and download of instrument data for further processing, etc.
The validation was performed with the following results:
1. The LAMP assays for detecting B. pertussis and S. pneumoniae have been validated independently of the integrated RESPOC system using bacterial DNA previously extracted and from clinical samples and purified. The assays demonstrated to have high diagnostic performance (sensitivity and specificity values in a range 90-100%).
2. The LAMP techniques run by the integrated RESPOC system using laboratory samples have only been partially assessed due to occurrence of random prototype failures that aborted such processes and resulted in invalid or inconclusive results. Limited available results prevent from driving conclusions about the diagnostic capabilities of the integrated system. A high proportion of false positive results were found within valid results (54.29%). False negative results distributed randomly across the concentrations 10^6-10^2 copies/mL.
3. It was observed that samples did not reach the amplification chamber of labcards in a high proportion of false-negative tests (84.21%) and that all true-positive tests (100%) were detected in labcards where samples reached the amplification chamber, even for low concentrations of 10^2 copies/mL. These observations are suggestive that the system is capable of performing with adequate sensitivity when random errors do not occur.
4. The LAMP assays detected B. pertussis and S. pneumoniae positive samples within 30 minutes since start of the amplification process, both when run by the integrated system and independently, proving to be at least 3-fold more rapid to perform the amplification step than reference PCR techniques. Considering the overall RESPOC sample in-result out process positives were detected within 60 minutes, which is a small fraction of the 150-180 minutes required for the conventional two-step DNA extraction and PCR amplification process
5. The integrated RESPOC system has demonstrated to be a simple easy-to-use instrument that can be operated after minimal training even by non specialised staff.
Tight communication among the RTDs was key during the project in order to harmonize the work, with the common goal to integrate all elements to be integrated into the final RESPOC instrument. The RTDs have counted with the constant supervision and advice from SMEs in monitoring that their requirements are fulfilled, ensuring the quality of the results. SMEs have had an active role in technology watch, keeping track of any new advances in the field.
Potential Impact:
The direct and indirect costs derived from pertussis and pneumonia pose a significant economic burden in terms of healthcare and social costs. Pneumococcal hospitalizations are estimated at a total of 1.2 million in USA and Europe. The number of hospitalizations in the case of pneumonia is much lower. A total of 15,749 cases of Bordetella pertussis was reported from the 28 European countries in 2010, with an overall incidence rate of 3.7 per 100,000 inhabitants, of which 84% were laboratory-confirmed cases. While vaccinations have reduced the impact of transmission, the pathogens still exist and continue to be highly contagious. The unavailability of efficient and fast analytical test to detect all potential cases is partly liable for the high impact of pertussis and pneumonia.
RESPOC has a number of competitive advantages over current detection methods: PCR has a cost that exceeds 30 €, requires specialized personnel and takes at least 4 hours for results. Cultivation cost is lower, but with a cultivation period of up to one week it can significantly increase hospitalization costs.
The cost of diagnostic tests accounts for 5-10% of the total cost per hospital case. RESPOC was conceived as a fast and low cost tool that will encourage an increase in testing. Early, low cost detection of the target pathogens, followed by adequate patient treatment, will allow to (i) reduce costs of laboratory testing, (ii) improve control and surveillance of target pathogens interrupting pathogen transmission and (iii) contribute to decrease length of hospital stay in non-intensive and intensive care units and associated costs. Estimated savings of €8 billion/year widely justify the expense on the RESPOC technology.
The initial target market of the proposed RESPOC platform includes primary hospitals with medium/large volumes of patients, especially if they include emergency, pediatric and/or geriatric wards. While initial commercialization efforts will be focused on the larger EU and US markets, in a future phase other markets will be targeted in areas of recurring incidence of pertussis and pneumonia outbreaks. The consortium will also take into consideration private laboratories as potential customers of the technology to provide services to smaller hospitals and other requests.
Early detection of target pathogens will help limit antibiotic overuse, which often results in increased drug costs that imply additional health-service costs and the emergence of new antibiotic resistant bacterial strains. The introduction of a low cost diagnostic test for severe respiratory infections with at least 85% sensibility and 90% specificity would save 229.000 children lives per year in developing countries with 50% access to effective hospital care.
The manufacture and commercialization of the RESPOC technology, as well as its application in hospitals and health centres has direct economic impact and strategic competitive impact for all SME proposers. All project partner SMEs will benefit directly from the profit deriving from sales revenues as technology providers or distributors. The partners will also benefit from the royalty payments from the Joint Venture Company managing the distribution of equipment and consumables.
List of Websites:
www.respoc.eu
Molecular techniques such as PCR (polymerase chain reaction) are becoming increasingly used for the detection of respiratory pathogens, due to their high accuracy and relatively fast turnaround time (hours). Their utilization can result in early and specific treatment, contribute to better patient outcomes and reduce length of hospital stay. However, implementation of rapid molecular diagnostics remains limited to large, centralised laboratories which can afford the requirements of dedicated PCR laboratory space, specialized personnel and costly equipment and consumables. Even in central laboratories, timely diagnosis may be undermined by delays during sample transport to the setting and batching practices oriented to save consumables. There is a need for a fast, cost-effective, user-friendly molecular diagnostic point-of-care (POC) instrument for near-patient use at small to medium size hospitals, and decentralized clinical laboratories. The RESPOC platform will be a novel solution designed to detect bacterial and viral respiratory pathogens in less than one hour. Based on the development of DNA extraction and DNA amplification methods integrated into a low-cost microfluidic lab-on-a-chip (LoC) consumable, the platform will deliver results automatically by insertion of the disposable LoC into a small footprint reading instrument. Initially it will identify the target respiratory pathogens Streptococcus pneumoniae (pneumococcus) and Bordetella pertussis. Pre-clinical validation and demonstration of the RESPOC instrument will be performed to ensure adequate diagnostic performance and usability.
Project Context and Objectives:
The World Health Organization recognizes infectious diseases as a major global health problem despite widespread prevention through vaccination, and the use of antibiotic therapy.
Two of the most prominent pathogens causing vaccine-preventable infections are Streptococcus pneumoniae (pneumococcus) and Bordetella pertussis.
The early diagnosis and prompt treatment of invasive pneumococcal disease (IPD) and pertussis is vital to prevent progression of illness to severe clinical manifestations such as complicated pneumonia, meningitis and sepsis. Additionally, early diagnosis also allows for improved surveillance and control of community and nosocomial outbreaks of highly contagious pertussis. Early detection and adequate treatment also enable a more cost-effective utilization of health care resources.
Molecular techniques such as PCR (polymerase chain reaction) are becoming increasingly used for the detection of respiratory pathogens, due to their high accuracy and relatively fast turnaround time (hours). Their utilization can result in early and specific treatment, contribute to better patient outcomes and reduce length of hospital stay. However, implementation of rapid molecular diagnostics remains limited to large, centralised laboratories which can afford the requirements of dedicated PCR laboratory space, specialized personnel and costly equipment and consumables. Even in central laboratories, timely diagnosis may be undermined by delays during sample transport to the setting and batching practices oriented to save consumables.
There is a need for a fast, cost-effective, user-friendly molecular diagnostic point-of-care (POC) instrument for near-patient use at small to medium size hospitals, and decentralized clinical laboratories. The RESPOC platform will be a novel solution designed to detect bacterial and viral respiratory pathogens in less than one hour. Based on the development of DNA extraction and DNA amplification methods integrated into a low-cost microfluidic lab-on-a-chip (LoC) consumable, the platform will deliver results automatically by insertion of the disposable LoC into a small footprint reading instrument. Initially it will identify the target respiratory pathogens Streptococcus pneumoniae (pneumococcus) and Bordetella pertussis.
The aim of the project is to develop a molecular analysis point-of-care (POC) diagnostic instrument which overcomes the limitations of the state of the art. The device will integrate and automatically perform detection of the target pathogens. It will enable sample collection and analysis in a time frame between 15 and 45 minutes.
To this end, the following tasks have been undertaken by the project RTDs (HSJD, HSG, ATEKNEA) under the leadership of the consortium SMEs:
• Design, develop and optimize, a sample collection protocol and an isothermal molecular assay for DNA extraction and amplification.
• Design and develop a low cost microfluidics cartridge that accepts direct biological samples from nasopharyngeal swabs (for B. pertussis) or blood (for pneumococcus) samples.
• Design and develop the complete POC instrument integrating all necessary elements for automation of the assay protocol and subsequent fluorescence detection.
• Integrate the above and perform a laboratory validation of the analytic characteristics of the assay and an in-field pre-clinical validation of its diagnostic characteristics and usability.
Project Results:
The RESPOC instrument integrates the following steps: sample introduction, optimized method for fast DNA extraction, selective DNA amplification by means of suitable isothermal methods and detection by optical fluorescence.
The consortium SMEs (NTL, JCB, SURESCREEN and PATHOFINDER) have entrusted the development of RESPOC to 3 high-profile European RTDs with complementary expertise: HSJD (molecular microbiology laboratory of tertiary-level hospital), HSG (microfluidics, lab-on-a-chip) and ATEKNEA (electromechanics, integration, software).
During the first 12 months of the project, some key milestones in the development of the RESPOC instrument were achieved. A survey prepared by the consortium members served as a means to assess the actual market demands of end users. In addition, extensive search on commercially available solutions allowed the consortium to identify the required features for the RESPOC instrument and to define the key specifications to be fulfilled.
Following the definition of specifications, each RTD made good progress in the tasks assigned to their respective field of expertise. The different elements that led to the final RESPOC instrument were fully defined. Tasks performed in parallel can be divided into 3 categories:
(i) Development and optimization of the NAAT assay, led by Hospital Sant Joan de Déu. An exhaustive review of the state of the art in amplification techniques was undertaken. The consortium selected LAMP as the NAAT for implementation in the cartridge. Different methods for DNA extraction, including innovative pulsed electric field technology, were tested to enhance DNA extraction. Sample collection protocols and transfer to the cartridge were defined. The work then focused in the development of the NAAT assay, including selection of the target sequences, primer design and testing and optimization of the assay protocols.
(ii) Design of the microfluidic cartridge (pre-storage of reagents, microfluidics layout, materials and interface with control/reading elements). HSG applied their experience on Lab-on-a-chip systems to the development of the RESPOC microfluidic cartridge. The design obeys the specifications yielded by the previous optimization of the assay in the lab, including reagent volumes, reagent storage, extraction and amplification temperatures, etc.
(iii) Development of instrument modules and software. Taking into account specifications and with the constant input from other active work packages, ATEKNEA designed the instrument architecture with the aim to provide the desired functionality in the most cost effective way. In addition, different commercial processor boards were evaluated and the most suitable solution was selected for integration in the RESPOC instrument.
Starting in M13, efforts were progressively focused on the development of the designed elements and the integration into the final RESPOC instrument, in order to provide a complete instrument for validation, which was performed in ATEKNEA facilities.
The development of a final design of the microfluidic layout of the LabCard was performed during the second period. and 92 + 46 LabCards were produced for validation purposes.
Considering the specifications and inputs from the WPs, the following modules were developed:
1) Power supply
2) Touch screen and processor board
3) Top rotor board
4) Cartridge boards
5) Main control board
6) Optical design
According to the specifications gathered in WP1, the fluorophore used to react with the respiratory pathogens is the FITC. This means that the excitation wavelength is approximately 490nm - 495nm and the emitted fluorescence is allocated at 520nm. The distance between wells is about 3.2mm and the well size is 4.8mm2. It has been taken into account that the maximum crosstalk between wells is less than 1%.
The excitation light is projected into the mirror at the cardholder, and from the mirror to the wells. The emitted fluorescence is caught by the photodiodes. Afterwards those signals must be conditioned electronically and processed by the microcontroller allocated at the main control board, however another PCB was developed for this purpose.
Three detectors were used to verify the cross talk: one located at the spatial filter and one located at each photodiode. The wells were artificially switched on and off and the power measured.
Furthermore, the motor (7) was developed. According to the movements and positioning that are necessary for reading the optical measurement a servo drive and a servo motor has been chosen.
The motor has been also changed owing to the load has been increased practically in 400g. The stipulated weight at the beginning was 820g. This is due to the increase of the CardHolder and the addition of 2 batteries.
These models have been tested and then implemented in the laboratory scale prototype. This has been necessary to ensure the correct performance of the fluidic with the cartridges in vertical position and also to check the correct operation of all PCBs and the communication between them.Then with feedbacks obtained with the laboratory scale, the final instrument housing was designed to integrate all components required.
In addition to this, the development of the instrument software has been carried out. The graphical user interface acts via the touch screen. This software will also enable communication between the instrument and outside systems via USB or Ethernet, to enable update of instrument software and download of instrument data for further processing, etc.
The validation was performed with the following results:
1. The LAMP assays for detecting B. pertussis and S. pneumoniae have been validated independently of the integrated RESPOC system using bacterial DNA previously extracted and from clinical samples and purified. The assays demonstrated to have high diagnostic performance (sensitivity and specificity values in a range 90-100%).
2. The LAMP techniques run by the integrated RESPOC system using laboratory samples have only been partially assessed due to occurrence of random prototype failures that aborted such processes and resulted in invalid or inconclusive results. Limited available results prevent from driving conclusions about the diagnostic capabilities of the integrated system. A high proportion of false positive results were found within valid results (54.29%). False negative results distributed randomly across the concentrations 10^6-10^2 copies/mL.
3. It was observed that samples did not reach the amplification chamber of labcards in a high proportion of false-negative tests (84.21%) and that all true-positive tests (100%) were detected in labcards where samples reached the amplification chamber, even for low concentrations of 10^2 copies/mL. These observations are suggestive that the system is capable of performing with adequate sensitivity when random errors do not occur.
4. The LAMP assays detected B. pertussis and S. pneumoniae positive samples within 30 minutes since start of the amplification process, both when run by the integrated system and independently, proving to be at least 3-fold more rapid to perform the amplification step than reference PCR techniques. Considering the overall RESPOC sample in-result out process positives were detected within 60 minutes, which is a small fraction of the 150-180 minutes required for the conventional two-step DNA extraction and PCR amplification process
5. The integrated RESPOC system has demonstrated to be a simple easy-to-use instrument that can be operated after minimal training even by non specialised staff.
Tight communication among the RTDs was key during the project in order to harmonize the work, with the common goal to integrate all elements to be integrated into the final RESPOC instrument. The RTDs have counted with the constant supervision and advice from SMEs in monitoring that their requirements are fulfilled, ensuring the quality of the results. SMEs have had an active role in technology watch, keeping track of any new advances in the field.
Potential Impact:
The direct and indirect costs derived from pertussis and pneumonia pose a significant economic burden in terms of healthcare and social costs. Pneumococcal hospitalizations are estimated at a total of 1.2 million in USA and Europe. The number of hospitalizations in the case of pneumonia is much lower. A total of 15,749 cases of Bordetella pertussis was reported from the 28 European countries in 2010, with an overall incidence rate of 3.7 per 100,000 inhabitants, of which 84% were laboratory-confirmed cases. While vaccinations have reduced the impact of transmission, the pathogens still exist and continue to be highly contagious. The unavailability of efficient and fast analytical test to detect all potential cases is partly liable for the high impact of pertussis and pneumonia.
RESPOC has a number of competitive advantages over current detection methods: PCR has a cost that exceeds 30 €, requires specialized personnel and takes at least 4 hours for results. Cultivation cost is lower, but with a cultivation period of up to one week it can significantly increase hospitalization costs.
The cost of diagnostic tests accounts for 5-10% of the total cost per hospital case. RESPOC was conceived as a fast and low cost tool that will encourage an increase in testing. Early, low cost detection of the target pathogens, followed by adequate patient treatment, will allow to (i) reduce costs of laboratory testing, (ii) improve control and surveillance of target pathogens interrupting pathogen transmission and (iii) contribute to decrease length of hospital stay in non-intensive and intensive care units and associated costs. Estimated savings of €8 billion/year widely justify the expense on the RESPOC technology.
The initial target market of the proposed RESPOC platform includes primary hospitals with medium/large volumes of patients, especially if they include emergency, pediatric and/or geriatric wards. While initial commercialization efforts will be focused on the larger EU and US markets, in a future phase other markets will be targeted in areas of recurring incidence of pertussis and pneumonia outbreaks. The consortium will also take into consideration private laboratories as potential customers of the technology to provide services to smaller hospitals and other requests.
Early detection of target pathogens will help limit antibiotic overuse, which often results in increased drug costs that imply additional health-service costs and the emergence of new antibiotic resistant bacterial strains. The introduction of a low cost diagnostic test for severe respiratory infections with at least 85% sensibility and 90% specificity would save 229.000 children lives per year in developing countries with 50% access to effective hospital care.
The manufacture and commercialization of the RESPOC technology, as well as its application in hospitals and health centres has direct economic impact and strategic competitive impact for all SME proposers. All project partner SMEs will benefit directly from the profit deriving from sales revenues as technology providers or distributors. The partners will also benefit from the royalty payments from the Joint Venture Company managing the distribution of equipment and consumables.
List of Websites:
www.respoc.eu