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Electrochemically-enabled high-throughput peptidomics for next-generation precision medicine

Periodic Reporting for period 1 - ElectroMed (Electrochemically-enabled high-throughput peptidomics for next-generation precision medicine)

Reporting period: 2020-01-01 to 2020-12-31

In the last decade, precision (or personalized) medicines have become relevant in the cure of high prevalence diseases, such as cancers and infections. Despite the growing number of technologies the development of individual-based treatments remains a very expensive and time consuming process. Recent scientific advances proved the potential of immunological treatments in the remissions of certain cancer types. In silico methods based on computer algorithms allow to identify peptides candidates enabling an efficient immune system response in the ght against cancers. However, those promising methods, based on prediction models, show a high rate of false positive results. In addition, the interactions between these molecules and the immune system cannot be fully characterized due to the enormous number of combinations, as well as the current instruments constraints to both spot and synthetize arrays of complex molecular entities while managing small quantities of reagents.
ElectroMed will provide a revolutionary technology for next generation precision medicine by developing the first fully-programmable in situ protein screening instrument. By designing a microfluidic-driven multiplexed platform, ElectroMed will enable a faster, affordable, and more efficient technology than current protein screening instruments. Consequently, this unprecedented device will significantly ease and reduce the price of protein screening. This proof-of-concept prototype will not only open the path to new personalized medicine applications, but it might also be of great interest for the food sector (e.g. food authenticity and traceability, GMOs or toxin detection), as well as for the environmental remediation or defense (e.g. detection of biological warfare agents).
The objective of ElectroMed is to build and validate a proof-of-concept prototype of a programmable high-throughput peptide microarray technology.
Electromed has also engaged to investigate COVID19 related peptide biomarkers and technology for detection.
UCPH generated a selection of peptides from the Cytomegalovirus (HHV-5) proteome, interacting with known human antibodies and MHC class II molecules. This list can be used in WP 1 and WP2 for experimenting in-situ synthesis and detection of peptide-protein interactions with FET, respectively
UCPH obtained in collaboration with University Hospital Copenhagen serum samples from COVID-19 and non COVID-19 patients. Novel peptide epitope targets were identified and selected for subsequent mapping a single residue level; analysed for inhibition of neutralizing anti-SARS-CoV2 antibodies and used to investigate the presence of peptide specific antibodies in a cohort of Covid-19 patients. The whole proteome data from all coronaviridae will be deposited on the Horizon Results Platform and results will be published
ELV developed a functional prototype for the sequential injection of multiple solutions using an Ibidi chip. Videos are available on our website. The system can be scaled up. This liquid management set up will be used for the liquid management of in-situ synthesis and the functionalization of multiplexed field effect sensors
LIST demonstrated electrochemical production of acidity. We explored different multiplexing strategies for acid control and reactions with organic solvents, demonstrating the efficiency of acid production in organic electrolytes and the in-situ deprotection of BOC groups from amine terminations. We demonstrated proton exchange reactions with electrodes with Teflon protection.
UPF developed the protocol for the coupling conditions of different amino acids on surfaces resembling the materials that will be used on our sensors including use of APTES functionalized porous glass beads that provide enough yield for HPLC-MS. A tetrapeptide was prepared and obtained in high purity by HPLC (94%). UPF also delivered peptides for the studies of COVID-19 antibody response within the study with UCPH
LIST optimized a protocol for the functionalization of sensor surface with peptides using SPR and monitored the density of adsorption of a multi-step functionalization. We implemented PNA receptors on silica substrate designed to capture viral COVID19 RNA sequences. PNA has a peptide basis common to other receptors to detect immune-interactions. Our assays with PNA receptors selectively detect COVID genetic material respect to other RNA strains. FET sensors can determine assays to capture mutations
LIST analysed the surface response of FinFETs from APTES functionalized and unmodified devices, respectively. A theoretical basis to determine the chemical properties of the surface by a pH titration. UoG automatized the FET response with an analytical model for pH sensing, which will be the base for the calculations of more complex experiments involving organic molecules and nanoparticle mediated sensing. We started numerical simulations to simulate the effects of fabrication in the reliability of the sensor
LIST develop the fabrication of FinFET devices at wafer scale using optical lithography and anisotropic etching to achieve FinFETs ranging from sub-100 nm to 300 nm lateral size. To adapt our current configurations of FINFETs with the PNA assays we developed a microfluidic platform for the integration of the FinFETs. The platform has three channels that could be used for three different functionalization that would include sensing channel, positive and negative controls. UoT has started the implementation of a new design using a planar Junctionless FET to increase the reliability of our sensors. These devices will be implemented to have a reliable response to be able to compare different devices
This European funded project aims to integrate electrochemical synthesis of peptide bioreceptors with sensitive Field Effect Transistors (FETs) in order to enable programmable in situ protein detection. We will make use of a system utilizing nano-litter chemistry on a chip for the functionalization of FinFETs which is a multi-gate device built on a substrate - sensors for high-performance data acquisition within a microfluidic-driven multiplexed platform for parallel screening. During this multidisciplinary project we will develop the concept of multiplexed electrochemical peptide synthesis (EPS), and improve the capabilities of FinFET sensors, in order to embed them into a unique cost-effective lab-on-chip prototype. The latter will be then validated by the researchers in laboratory-relevant conditions for the screening of peptide sequences in cancer vaccines.

Our technology can create faster diagnosis with improvements on efficient field effect biosensors compatibles with silicon technology that can be mass produced. We aspire to facilitate with our platform the introduction of cancer vaccines for precision medicine with the possibility of protein screening with fast tailored peptide microarrays. This kind of technology has the potential to provide the European companies an advantage in the market of precision medicine diagnosis and the creation of tailored treatments.
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