COVID 19BIOPLEXNCT06702540
Bio-reconfigurable Electronic Platform for Multiplex Detection of Viral Respiratory Pathogens
An observational study of COVID 19, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
This project focuses on developing a cutting-edge electronic biosensor platform for highly sensitive and specific detection of target biomolecules, with initial applications targeting SARS-CoV-2 detection. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- COVID 19
- What is being tested?
- Biosensor chip
- Type of treatment
- Medical device
- How many people
- 158 participants
- Where
- 1 siteItaly
- Study dates
- 19 Mar 2020to 28 Sep 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: No patients or use of clinical data will be involved for the study, but only used the samples stored in the San Raffaele institutional COVID-19 clinical-biological biobank (COVID-BioB, NCT04318366). The samples used for the study were collected during the period 19/03/2020 - 31/05/2024.
Who may be able to join
- Samples tested for respiratory viruses, stored at the San Raffaele institutional COVID-19 clinical-biological biobank (COVID-BioB, NCT04318366).
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bio-reconfigurable Differential Impedance Electronic Platform for High Sensitivity Multiplex Detection of Viral Respiratory Pathogens
This project focuses on developing a cutting-edge electronic biosensor platform for highly sensitive and specific detection of target biomolecules, with initial applications targeting SARS-CoV-2 detection. The system operates on impedance measurement between microelectrodes, utilizing lock-in mode for unparalleled resolution (1 ppm). Enhanced signal detection is achieved via functionalized polystyrene microbeads that amplify impedance changes, building on prior success in Dengue virus antibody detection.
Key innovations include Differential Impedance Sensing across multiple channels for real-time comparative analysis of various targets, and a biosensor chip modified with DMA-based functional polymers for optimal probe immobilization and target interaction. The biosensor integrates with a pre-existing microfluidic system and supports whole-virus detection using DNA-labelled antibodies against SARS-CoV-2 spike protein, coupled with complementary oligonucleotide-functionalized beads. This strategy is complemented by antigen-specific detection for practical applications such as point-of-care testing in pharmacies.
The project includes a retrospective study analyzing anonymized respiratory and plasma samples from a COVID-19 biobank to validate the platform's sensitivity in detecting viral particles. These efforts aim to advance diagnostic technologies for respiratory infections with a focus on safety, scalability, and versatility.
Read the detailed description
The project stands on the development of an electronic platform performing the measurement of the impedance variation between microelectrodes upon the capture of the target biomolecule by a selective bioprobe previously grafted over the biosensor surface. The required sensitivity will be achieved by operating the biosensor in lock-in mode, which ensures the highest resolution in tracking amplitude and phase variations of impedance signals (1 ppm has been demonstrated by POLIMI on other applications). To enhance the electronic signal, polystyrene microbeads, properly functionalized with oligonucleotides or antibodies, are used to link the target and increase the impedance variation as demonstrated by proponents in the successful detection of antibodies against Dengue virus. To address multiple sensing sites in parallel on the same biosensor chip, allowing real-time comparative analysis on different targets from the same biological sample for augmented detection sensitivity and control, a custom-made electronic platform will be developed to perform Differential Impedance Sensing (i.e., direct comparison between the target sensor and a reference) on multiple channels. The biosensor chip, made of borosilicate with gold microelectrodes, features a specific modification of its surface with functional polymers (a family of N,N-dimethylacrylamide -DMA-based polymers) developed by CNR that form a nanometric hydrophilic film on the chip surface. The functional groups of these copolymers allow the covalent immobilization of the probe preserving its active structure, proper spatial distance, orientation and density, favoring the interaction with the target. The biosensor chip will be integrated into the microfluidic system already available in the group.
SARS-CoV-2 will be targeted with challenging strategies. First, we plan to capture the entire virus in solution using DNA-labelled antibodies directed against the SARS-CoV-2 spike protein.
The sensor area, spotted with oligonucleotide probes complementary to the DNA sequence linked to the antibody, will interact with the DNA-labelled antibodies which have decorated the entire surface of the virus. To increase the impedance variation of the platform polystyrene beads will be used: in particular, they will be modified with the oligonucleotide complementary to that linked to the antibody which have captured the virus. This entire-virus detection methodology, combining the DNA-directed capture of the antigens together with a high sensitivity platform for Differential Impedance Sensing, is absolutely new and expected to be successful based upon the results already achieved by the proponents in the detection of the antibodies in the human blood of persons infected by Dengue virus. In parallel, we intend to extend the use of the electronic platform also to the detection of viral antigens, i.e. Spike protein S or nucleocapside protein N. The use of antigens for the diagnosis of the infection instead of the entire virus, may lead to important practical dropouts as it does not necessitate any particular safety requirement, thus allowing the test to be performed in any location, in particular pharmacies or medical clinics similarly to standard antigenic lateral flow tests.
This is a retrospective monocenter study to test respiratory samples to evaluate the analytical sensitivity of the platform being developed in the project PRIN Prot. 2022EJL28B. The samples are completed anonymized and the samples analyses are performed in order to check the ability of the device to reveal the presence of viral particles in biological matrix such as respiratory samples or, when necessary for set up of instruments, plasma randomized and anonymized samples. No patients or use of clinical data will be involved for the study, but only used the samples stored in the San Raffaele institutional COVID-19 clinical-biological biobank (COVID-BioB, NCT04318366). The samples used for the study were collected during the period 19/03/2020 - 31/05/2024.
- Conditions
- COVID 19
- Being tested
- Biosensor chip
- Keywords
- COVID-19, SARS-CoV-2, Biosensor chip
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biosensor chipDevice
An electronic platform measuring the impedance variation between microelectrodes is used upon capturing the target biomolecule by a selective bioprobe previously grafted over the biosensor surface. The required sensitivity will be achieved by operating the biosensor in lock-in mode, which ensures the highest resolution in tracking amplitude and phase variations of impedance signals.
| Study group | Role | What they receive |
|---|---|---|
| Positive for respiratory viruses | 79 retrospective samples tested positive for respiratory viruses Receives: Device: Biosensor chip | |
| Negative to respiratory viruses | 79 retrospective samples tested negative to respiratory viruses Receives: Device: Biosensor chip |
What is being measured
The primary outcome is the main question the study is designed to answer.
Validation of the biosensor platform with nasopharyngeal swabs
Real-time impedance measurement in randomized respiratory samples to detect respiratory viruses
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2024
- Study start19 Mar 2020
- Primary completion31 May 2024
- Study completion28 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for COVID 19Studies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 158 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- Politecnico di Milano, Consiglio Nazionale delle Ricerche, Italy
- Responsible party
- Principal investigator, Nicola Clementi, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06702540
- Sponsor's protocol ID
- BIOPLEX 2022EJL28B
- Other IDs
- 2022EJL28B
- Acronym
- BIOPLEX
- Status last verified
- Nov 2024
- First submitted
- 18 Nov 2024
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liu W, Liu L, Kou G, Zheng Y, Ding Y, Ni W, Wang Q, Tan L, Wu W, Tang S, Xiong Z, Zheng S. Evaluation of Nucleocapsid and Spike Protein-Based Enzyme-Linked Immunosorbent Assays for Detecting Antibodies against SARS-CoV-2. J Clin Microbiol. 2020 May 26;58(6):e00461-20. doi: 10.1128/JCM.00461-20. Print 2020 May 26.
PubMed 32229605Seo G, Lee G, Kim MJ, Baek SH, Choi M, Ku KB, Lee CS, Jun S, Park D, Kim HG, Kim SJ, Lee JO, Kim BT, Park EC, Kim SI. Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor. ACS Nano. 2020 Apr 28;14(4):5135-5142. doi: 10.1021/acsnano.0c02823. Epub 2020 Apr 20.
PubMed 32293168Sola L, Damin F, Gagni P, Consonni R, Chiari M. Synthesis of Clickable Coating Polymers by Postpolymerization Modification: Applications in Microarray Technology. Langmuir. 2016 Oct 11;32(40):10284-10295. doi: 10.1021/acs.langmuir.6b02816. Epub 2016 Sep 29.
PubMed 27632284Piedimonte P, Sola L, Cretich M, Gori A, Chiari M, Marchisio E, Borga P, Bertacco R, Melloni A, Ferrari G, Sampietro M. Differential Impedance Sensing platform for high selectivity antibody detection down to few counts: A case study on Dengue Virus. Biosens Bioelectron. 2022 Apr 15;202:113996. doi: 10.1016/j.bios.2022.113996. Epub 2022 Jan 15.
PubMed 35091373F. Morichetti et al., "Non-Invasive On-Chip Light Observation by Contactless Waveguide Conductivity Monitoring," in IEEE Journal of Selected Topics in Quantum Electronics, vol. 20, no. 4, pp. 292-301, July-Aug. 2014, Art no. 8201710, doi: 10.1109/JSTQE.2014.2300046.
Ciccarella, Pietro et al. "Multichannel 65 zF rms Resolution CMOS Monolithic Capacitive Sensor for Counting Single Micrometer-Sized Airborne Particles on Chip." IEEE Journal of Solid-State Circuits 51 (2016): 2545-2553.
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bio-reconfigurable Differential Impedance Electronic Platform for High Sensitivity Multiplex Detection of Viral Respiratory Pathogens
- ClinicalTrials.gov ID
- NCT06702540
- Acronym / sponsor ID
- BIOPLEX / BIOPLEX 2022EJL28B
- Conditions
- COVID 19
- Keywords
- COVID-19, SARS-CoV-2, Biosensor chip
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 158 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- Politecnico di Milano, Consiglio Nazionale delle Ricerche, Italy
- Study start
- 19 Mar 2020 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 28 Sep 2025 (estimated)
- First posted
- 25 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project focuses on developing a cutting-edge electronic biosensor platform for highly sensitive and specific detection of target biomolecules, with initial applications targeting SARS-CoV-2 detection. The system operates on impedance measurement between microelectrodes, utilizing lock-in mode for unparalleled resolution (1 ppm). Enhanced signal detection is achieved via functionalized polystyrene microbeads that amplify impedance changes, building on prior success in Dengue virus antibody detection.
Key innovations include Differential Impedance Sensing across multiple channels for real-time comparative analysis of various targets, and a biosensor chip modified with DMA-based functional polymers for optimal probe immobilization and target interaction. The biosensor integrates with a pre-existing microfluidic system and supports whole-virus detection using DNA-labelled antibodies against SARS-CoV-2 spike protein, coupled with complementary oligonucleotide-functionalized beads. This strategy is complemented by antigen-specific detection for practical applications such as point-of-care testing in pharmacies.
The project includes a retrospective study analyzing anonymized respiratory and plasma samples from a COVID-19 biobank to validate the platform's sensitivity in detecting viral particles. These efforts aim to advance diagnostic technologies for respiratory infections with a focus on safety, scalability, and versatility.
Detailed description
The project stands on the development of an electronic platform performing the measurement of the impedance variation between microelectrodes upon the capture of the target biomolecule by a selective bioprobe previously grafted over the biosensor surface. The required sensitivity will be achieved by operating the biosensor in lock-in mode, which ensures the highest resolution in tracking amplitude and phase variations of impedance signals (1 ppm has been demonstrated by POLIMI on other applications). To enhance the electronic signal, polystyrene microbeads, properly functionalized with oligonucleotides or antibodies, are used to link the target and increase the impedance variation as demonstrated by proponents in the successful detection of antibodies against Dengue virus. To address multiple sensing sites in parallel on the same biosensor chip, allowing real-time comparative analysis on different targets from the same biological sample for augmented detection sensitivity and control, a custom-made electronic platform will be developed to perform Differential Impedance Sensing (i.e., direct comparison between the target sensor and a reference) on multiple channels. The biosensor chip, made of borosilicate with gold microelectrodes, features a specific modification of its surface with functional polymers (a family of N,N-dimethylacrylamide -DMA-based polymers) developed by CNR that form a nanometric hydrophilic film on the chip surface. The functional groups of these copolymers allow the covalent immobilization of the probe preserving its active structure, proper spatial distance, orientation and density, favoring the interaction with the target. The biosensor chip will be integrated into the microfluidic system already available in the group.
SARS-CoV-2 will be targeted with challenging strategies. First, we plan to capture the entire virus in solution using DNA-labelled antibodies directed against the SARS-CoV-2 spike protein.
The sensor area, spotted with oligonucleotide probes complementary to the DNA sequence linked to the antibody, will interact with the DNA-labelled antibodies which have decorated the entire surface of the virus. To increase the impedance variation of the platform polystyrene beads will be used: in particular, they will be modified with the oligonucleotide complementary to that linked to the antibody which have captured the virus. This entire-virus detection methodology, combining the DNA-directed capture of the antigens together with a high sensitivity platform for Differential Impedance Sensing, is absolutely new and expected to be successful based upon the results already achieved by the proponents in the detection of the antibodies in the human blood of persons infected by Dengue virus. In parallel, we intend to extend the use of the electronic platform also to the detection of viral antigens, i.e. Spike protein S or nucleocapside protein N. The use of antigens for the diagnosis of the infection instead of the entire virus, may lead to important practical dropouts as it does not necessitate any particular safety requirement, thus allowing the test to be performed in any location, in particular pharmacies or medical clinics similarly to standard antigenic lateral flow tests.
This is a retrospective monocenter study to test respiratory samples to evaluate the analytical sensitivity of the platform being developed in the project PRIN Prot. 2022EJL28B. The samples are completed anonymized and the samples analyses are performed in order to check the ability of the device to reveal the presence of viral particles in biological matrix such as respiratory samples or, when necessary for set up of instruments, plasma randomized and anonymized samples. No patients or use of clinical data will be involved for the study, but only used the samples stored in the San Raffaele institutional COVID-19 clinical-biological biobank (COVID-BioB, NCT04318366). The samples used for the study were collected during the period 19/03/2020 - 31/05/2024.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Positive for respiratory viruses | – | Device: Biosensor chip79 retrospective samples tested positive for respiratory viruses |
| Negative to respiratory viruses | – | Device: Biosensor chip79 retrospective samples tested negative to respiratory viruses |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- No patients or use of clinical data will be involved for the study, but only used the samples stored in the San Raffaele institutional COVID-19 clinical-biological biobank (COVID-BioB, NCT04318366). The samples used for the study were collected during the period 19/03/2020 - 31/05/2024.
Key inclusion criteria (1 listed)
- Samples tested for respiratory viruses, stored at the San Raffaele institutional COVID-19 clinical-biological biobank (COVID-BioB, NCT04318366).
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biosensor chipAn electronic platform measuring the impedance variation between microelectrodes is used upon capturing the target biomolecule by a selective bioprobe previously grafted over the biosensor surface. The required sensitivity will be achieved by operating the biosensor in lock-in mode, which ensures the highest resolution in tracking amplitude and phase variations of impedance signals. | Device | Negative to respiratory viruses, Positive for respiratory viruses |
Primary outcome
Validation of the biosensor platform with nasopharyngeal swabs
Time frame: 12 months
Real-time impedance measurement in randomized respiratory samples to detect respiratory viruses
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Background: PubMed 32229605Liu W, Liu L, Kou G, Zheng Y, Ding Y, Ni W, Wang Q, Tan L, Wu W, Tang S, Xiong Z, Zheng S. Evaluation of Nucleocapsid and Spike Protein-Based Enzyme-Linked Immunosorbent Assays for Detecting Antibodies against SARS-CoV-2. J Clin Microbiol. 2020 May 26;58(6):e00461-20. doi: 10.1128/JCM.00461-20. Print 2020 May 26.
- Background: PubMed 32293168Seo G, Lee G, Kim MJ, Baek SH, Choi M, Ku KB, Lee CS, Jun S, Park D, Kim HG, Kim SJ, Lee JO, Kim BT, Park EC, Kim SI. Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor. ACS Nano. 2020 Apr 28;14(4):5135-5142. doi: 10.1021/acsnano.0c02823. Epub 2020 Apr 20.
- Background: PubMed 27632284Sola L, Damin F, Gagni P, Consonni R, Chiari M. Synthesis of Clickable Coating Polymers by Postpolymerization Modification: Applications in Microarray Technology. Langmuir. 2016 Oct 11;32(40):10284-10295. doi: 10.1021/acs.langmuir.6b02816. Epub 2016 Sep 29.
- Background: PubMed 35091373Piedimonte P, Sola L, Cretich M, Gori A, Chiari M, Marchisio E, Borga P, Bertacco R, Melloni A, Ferrari G, Sampietro M. Differential Impedance Sensing platform for high selectivity antibody detection down to few counts: A case study on Dengue Virus. Biosens Bioelectron. 2022 Apr 15;202:113996. doi: 10.1016/j.bios.2022.113996. Epub 2022 Jan 15.
- BackgroundF. Morichetti et al., "Non-Invasive On-Chip Light Observation by Contactless Waveguide Conductivity Monitoring," in IEEE Journal of Selected Topics in Quantum Electronics, vol. 20, no. 4, pp. 292-301, July-Aug. 2014, Art no. 8201710, doi: 10.1109/JSTQE.2014.2300046.
- BackgroundCiccarella, Pietro et al. "Multichannel 65 zF rms Resolution CMOS Monolithic Capacitive Sensor for Counting Single Micrometer-Sized Airborne Particles on Chip." IEEE Journal of Solid-State Circuits 51 (2016): 2545-2553.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID 19, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Validation of the biosensor platform with nasopharyngeal swabs (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06702540, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.