New opportunities for nanotechnology in the field of diagnostics based on proteomics

New developments in personalised medicine pose a technological challenge for the implementation of diagnostic devices demanding an increase for the speed, throughput and sensitivity for the detection of proteomic biomarkers. Following the tracks of genetics where the progress came through the analysis of DNA fragments, peptides, which are small fragments of proteins, can provide a new tool to get insights into the analysis of macromolecules. However, the current methods of combinatorial chemistry and sensing based on liquid handling and labelling, respectively, cannot cope with the demands of throughput and speed required by clinical applications. Nanotechnology holds promises to improve in-situ synthesis of microarrays and label free sensing to provide the combinatorial flexibility, quickness and sensitivity to help for the implementation of proteomic diagnosis in precision medicine. *Correspondence to: García CP, Nano-Enabled Medicine and Cosmetics group, Materials Research and Technology Department, Luxembourg Institute of Science and Technology (LIST), 41, rue du Brill, Belvaux, Luxembour, E-mail: cesar.pascual@list.lu Special Issue: Nanotechnology: Challenges and Perspectives in Medicine Dr. Federica Valentini Department of Sciences and Chemical Technologies Tor Vergata University Italy Maurizio Talamo Professor Department of Enterprise Engineering Italy Received: November 25, 2018; Accepted: December 20, 2018; Published: December 24, 2018 Introduction During the last decade, personalised medicines have progressed due to an unprecedented penetration of clinical devices for molecular diagnostics [1]. Most of these instruments like the next generation sequencers (NGS’s) or point of care diagnosis (PoCdx) devices based on polymerase chain reaction (PCR) (like the Biofire Film Array, Genemark e-sensor, Luminex xTAG or Biocartis Idylla devices) operate in the field of genetics. At the base of this progress, there is an accurate manipulation of DNA. Outstanding examples of technology helping the decision makig of personalised diagnosis are the DNA sequencers developed by the former Ion Torrent instrument (currently Thermofisher) [2] or Oxford Nanopore [3], that demonstrated that electrochemical sensing can be used to deliver high-throughput quality data in a compact cost-efficient tool. Immunologist use now these kind of instruments combined with in-silico techniques to find alterations on the genes responsible of making proteins, driving developments that open the door to new therapies. The prospect of the post-genomic era is an improvement driven by proteomics. While genes can contain misleading structural of un-expressed information, proteomic biomarkers can provide more representative information of the cell activity revealing not only a more accurate diagnostic, but also an indication of the therapeutic drug by revealing the proteins that could be used in a possible vaccine [4]. However, the chemical control of proteins is not jet as good as the one of DNA, which hampers the progress of immunosensors for the implementation of proteomics at clinical level. Mass-spectrometry is nowadays the main tool for the analysis in research, but is not able to cope with the required amount of information needed for clinical decisions. In hospitals enzymes used in ELISA and antibodies for immunostaining provide some of the most sensitive and selective tests, but they are still generic tools not tune to the personal profile. Precision medicine is demanding a higher and more complex analysis of proteins at the hospital level. A possibility to address the required combinatorial diversity is to use smaller entities made by combination of the constituent amino acids, peptides. Peptides can provide a very rich variety of chemical combinations. With only 15 amino acids (a.a.’s) the number of possible combinations (>1027) is much bigger than the number of transistors shipped ever since the technology was invented (>1021). This diversity can only be addressed with flexible programmable molecular libraries, which are in the case of these molecules peptide microarrays. Peptide microarrays can hold in fact the potential to detect, differentiate and characterize proteins providing significant biological information [5,6]. In addition to the complexity and variability of proteins, protein diagnostics face the ultralow concentrations at which these molecules are found in biological conditions in the absence of molecular preamplification like in the case of DNA. Therefore, the assays have to employ ultra-sensitive transducers preferably with label free sensing. Nanostructured sensors open new perspectives since their size is comparable to the molecules to detect reaching good sensitivities with ultralow concentrations [7]. However few of these sensors are García CP (2018) New opportunities for nanotechnology in the field of diagnostics based on proteomics Volume 5(1): 2-4 Front Nanosci Nanotech, 2018 doi: 10.15761/FNN.1000S2001 candidates to be used for multiplexing the high number of spots present in peptide microarrays. Currently, plasmonic or highly sensitive field effect transistors (FETs) are the main candidates that can provide the miniaturisation necessary to offer hundreds of thousands of features per cm2. The biggest obstacle found by nanostructure nanosensors has been their standardisation that makes them reliable for clinical uses. An improved chemical manipulation of proteomic entities combined with label free techniques is the request to implement proteomic diagnostics for personalised medicine. If the use of peptides is the chosen route, the challenge is producing high-throughput programmable peptide microarrays to study the possible interactions of proteins that can translate relevant clinical information. Currently peptide microarrays are still expensive and unreliable for their use in clinical diagnostics. They can benefit from the use of nanotechnologies to increase their yield and efficiency. As nanotechnologies are also rapidly advancing lowering the limits of detection of molecules in biological tissues and fluids now it seems possible that these tests will help in the decision making of clinicians in the next future. Here we review at glance the current technologies for the synthesis of microarrays and sensitive label free sensing in which nanotechnology can help to improve to provide the next generation diagnostic tools.