Tomáš Bertók

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• Doctor of Philosophy
• Senior Research Scientist at Slovak Academy of Sciences

Herein, the basic properties, composition, and isolation methods for the separation of exosomes are described, since they can be a rich source of disease biomarkers. Then an introduction to MXenes, a novel class of 2D nanomaterials with interesting properties applicable in numerous fields including biosensing is provided. Also, aptamers are describ...

The review article provides a short introduction to exosomes with the focus to use exosomes as disease markers itself (i.e. their concentration or presence of some specific receptors) or a source of disease biomarkers such as proteins and metabolites. In detail, we are discussing various methods of exosome isolation and the main focus of the review...

Post-translational modifications of proteins play an important role in their stability, solubility and in vivo function. Also, for several reasons, such as the Golgi fragmentation during cancerogenesis, glycosylation as the most common modification is especially promising in offering high cancer specificity which, in combination with tissue-specifi...

Background The medication used to treat benign prostate hyperplasia (BPH), a common condition in men over 50 years of age, can alter the levels of biomarkers used in prostate cancer detection. Commonly used medications for BPH include alpha‐blockers, 5‐alpha reductase inhibitors (5‐ARIs), and muscarinic antagonists. We studied the impact of these d...

This review briefly introduces readers to an area where glycomics meets modern oncodiagnostics with a focus on the analysis of sialic acid (Neu5Ac)-terminated structures. We present the biochemical perspective of aberrant sialylation during tumourigenesis and its significance, as well as an analytical perspective on the detection of these structure...

The glycoprofiling of two proteins, the free form of the prostate-specific antigen (fPSA) and zinc-α-2-glycoprotein (ZA2G), was assessed to determine their suitability as prostate cancer (PCa) biomarkers. The glycoprofiling of proteins was performed by analysing changes in the glycan composition on fPSA and ZA2G using lectins (proteins that recogni...

Prostate cancer (PCa) is the second most common cancer. In this paper, the isolation and properties of exosomes as potential novel liquid biopsy markers for early PCa liquid biopsy diagnosis are investigated using two prostate human cell lines, i.e., benign (control) cell line RWPE1 and carcinoma cell line 22Rv1. Exosomes produced by both cell line...

The glycoprofiling of two proteins, the free form of the prostate-specific antigen (fPSA) and zinc-α-2-glycoprotein (ZA2G), was assessed to determine their suitability as prostate cancer (PCa) biomarkers. The glycoprofiling of proteins was performed by analysing changes in the glycan composition on fPSA and ZA2G using lectins (proteins recognising...

This review provides a comprehensive overview of our understanding of the role that glycans play in the formation, loading and release of extracellular vesicles (EVs). The capture of EVs (typically with a size of 100-200 nm) is described, including approaches based on glycan recognition with glycan-based analysis offering highly sensitive detection...

Exosomes are considered to be a rich source of biomarkers, hence in this article we examine the best procedure for their isolation. We examine several isolation procedures, exosome storage conditions and other conditions affecting exosome production by prostate cell lines. We selected four different commercially available kits based on different pr...

Background: Testicular cancer (TC) is the most frequent type of cancer among young men aged between 15 and 34 years. TC is treated using cisplatin, but 3%-5% of TC patients fail to respond to cisplatin, with a very bad to fatal prognosis. Accordingly, it is most important to quickly and readily identify those TC patients who are resistant to cispl...

Colorectal cancer (CRC) is one of the most common types of cancer among men and women worldwide. Efforts are currently underway to find novel and more cancer-specific biomarkers that could be detected in a non-invasive way. The analysis of aberrant glycosylation of serum glycoproteins is a way to discover novel diagnostic and prognostic CRC biomark...

The review initially provides a short introduction to prostate cancer (PCa) incidence, mortality, and diagnostics. Next, the need for novel biomarkers for PCa diagnostics is briefly discussed. The core of the review provides details about PCa aetiology, alternative biomarkers available for PCa diagnostics besides prostate specific antigen and their...

In the field of printed electronics, carbon and its allotropes are today among the most studied materials due to their unique physical and chemical properties. In this work, carbon dispersions were used for the preparation of screen-printed carbon electrodes applied as counter electrodes (CEs) for the dye-sensitized solar cells and as working elect...

Prostate cancer (PCa) is one of the most common cancer types among men and also a common cause of death globally. With an increasing incidence, there is a need for low-cost, reliable biomarkers present in samples, which could be provided non-invasively (without a need to perform prostate biopsy). Glycosylation changes of free-PSA (fPSA) are conside...

The review provides articles discussing big challenges behind successful design of impedimetric biosensors and the way such challenges were/could be addressed for highly sensitive affinity detection of proteins. In particular, the effect of gold etching by chloride ions or by CN⁻ ions (released from the redox probe [Fe(CN)6]3-/4-), the effect of io...

This is the first work focused on glycoprofiling of whole N- and O- glycome using lectins in an array format applied for analysis of serum samples from healthy individuals, benign prostate hyperplasia (BPH) patients, and prostate cancer (PCa) patients. Lectin microarray was prepared using traditional lectins with the incorporation of 2 recombinant...

Background: To compare the clinical performance of a new PCa serum biomarker based on fPSA glycoprofiling to fPSA% and PHI. Methods: Serum samples from men who underwent prostate biopsy due to increased PSA were used. A comparison between two equal groups (with histologically confirmed PCa or benign, non-cancer condition) was used for the clinical...

For efficient and effective utilization of MXene such as biosensing or advanced applications, interfacial modification of MXene needs to be considered. To this end, we describe modification of Ti3C2Tx MXene by aryldiazonium-based grafting with derivatives bearing a sulfo- (SB) or carboxy- (CB) betaine pendant moiety. Since MXene contains free elect...

Two-dimensional layered nanomaterial Ti3C2TX (a member of the MXene family) was used to immobilise enzyme sarcosine oxidase to fabricate a nanostructured biosensor. The device was applied for detection of sarcosine, a potential prostate cancer biomarker, in urine for the first time. The morphology and structures of MXene have been characterised by...

Invited for this month's cover picture is the group of Dr. Jan Tkac (head of the Department of Glycobiotechnology at the Institute of Chemistry at the Slovak Academy of Sciences, Slovakia). The cover picture shows a common eukaryotic cell with basic organelles, as well as intracellular formation/preparation of exosomes for express delivery to dista...

The Front Cover illustrates a common eukaryotic cell with basic organelles, as well as intracellular formation/preparation of exosomes for express delivery to distant tissues.More information can be found in the Review by L. Lorencova et al.

Exosomes are naturally produced biological nanoparticles secreted by cells into body fluids and responsible for intercellular communication. Exosomes can also carry cargo affecting neighbouring cells and forming pre‐metastatic niches. Hence, exosomes are behind localised tumour development, progression, but also the induction of distant tumours for...

Glycomics (a comprehensive study of glycans, often denoted as the third alphabet of molecular biology, besides nucleic acids and proteins) relies on techniques that use "heavy machinery", such as mass spectrometry, liquid chromatography, and capillary electrophoresis. The use of biosensors and biochips for glycan analysis offers the possibility of...

2D MXenes as Perspective Immobilization Platforms for Design of Electrochemical Nanobiosensors. More details can be found in the Full Paper by Ludmila Šimková, Jan Svoboda, Jiři Pinkas, et al. (DOI: 10.1002/elan.201900288).

The article describes preparation, characterization and further modification of hybrid magnetic particles (Au nanoshells with a magnetic core (MPs@silica@Au)) by zwitterionic molecules bearing diazonium functional groups. Such hybrid magnetic particles modified by zwitterionic molecules exhibit the following features: •Responsiveness towards extern...

MXenes are a new group of 2D nanomaterials with fascinating properties including high electrical conductivity, hydrophilic nature, easily tunable structure and high surface area. This is why MXene modified interfaces are extremely promising for the preparation of sensitive electrochemical biosensors. While there are numerous reports on MXene‐based...

The initial part of this review details the controversy behind the use of a serological level of prostate-specific antigen (PSA) for the diagnostics of prostate cancer (PCa). Novel biomarkers are in demand for PCa diagnostics, outperforming traditional PSA tests. The review provides a detailed and comprehensive summary that PSA glycoprofiling can e...

In this paper several advances were implemented for glycoprofiling of prostate specific antigen (PSA), what can be applied for better prostate cancer (PCa) diagnostics in the future: 1) application of Au nanoshells with a magnetic core ([email protected]@Au); 2) use of surface plasmons of Au nanoshells with a magnetic core for spontaneous immobiliz...

In this work, the spontaneous and NaBH4-induced reduction of chloroplatinic acid on the surface of Ti3C2TX MXene was investigated to synthesize a hybrid PtNP-decorated MXene nanomaterial (MX-Pt) with potential as hydrogen evolution (HER) or oxygen reduction reaction (ORR) catalyst properties. The initial Pt concentration, reduction time and presenc...

The Cover Feature shows integration of electrochemical impedance spectroscopy for the analysis of clinically relevant samples toward cancer diagnostics.More information can be found in the Review by T. Bertok et al.

Introduction: Prostate cancer (PCa) is a life-threatening disease affecting millions of men. The current best PCa biomarker (level of prostate-specific antigen in serum) lacks specificity for PCa diagnostics and this is why novel PCa biomarkers in addition to the conventional ones based on biomolecules such as DNA, RNA and proteins need to be iden...

Impedimetric affinity biosensors are, without any doubt, among the most sensitive analytical devices available, offering low limits of detection and wide linear response ranges. There are, however, few papers detailing the application of impedimetric biosensors for the analysis of clinically relevant samples with due clinical performance. The fact...

There are two key novel components presented here behind identification of potential novel breast cancer (BCa) diagnostic approach: 1. application of photoimmobilizable zwitterionic hydrogels resisting non-specific protein adsorption for preparation of the biosensor interfaces and 2. integration of lectins (carbohydrate recognizing proteins) within...

Electrochemical performance of a 2D Ti3C2Tx (MXene, where T: [dbnd]O, –OH, –F) sheets modified with Pt nanoparticles (PtNPs) was investigated. The results showed that Ti3C2Tx/PtNP nanocomposite deposited on the surface of GCE showed much better and stable redox behavior in an anodic potential window as compared to the GCE modified with pristine Ti3...

In this study, one hundred serum samples from healthy people and patients with rheumatoid arthritis (RA) were analyzed. Standard immunoassays for detection of 10 different RA markers and analysis of glycan markers on antibodies in 10 different assay formats with several lectins were applied for each serum sample. A dataset containing 2000 data poin...

Films made of xylan (X) and quaternized chitosan (QC) were prepared and the interactions of the polysaccharides on interfaces were discussed. According to elemental analysis, the X film contained also cellulose (31%) which could not be separated from the water suspension. The QC sample was soluble in water due to the presence of quaternized glucosa...

In this study, two quaternary ammonium salts derived from l-lipoic acid were applied for self-assembled monolayers formation on rough structured gold surface. The derivatives differ in functionality since one possesses simple quaternary ammonium group whereas the other one is carboxybetaine ester containing quaternary ammonium group with pH hydroly...

Screening serum for the presence of prostate specific antigen (PSA) belongs to the most common approach for the detection of prostate cancer. This review (with 156 refs.) addresses recent developments in PSA detection based on the use of various kinds of nanomaterials. It starts with an introduction into the field, the significance of testing for P...

We describe a self-assembled monolayer (SAM) on a gold surface with carboxybetaine ester functionality to control the interaction between DNA and gold nanoparticles via pH. The negatively charged phosphate backbone of DNA interacts with and adsorbs to the positively charged carboxybetaine esters on the SAM. DNA release can be achieved by the hydrol...

In recent decades, it has become clear that most of human proteins are glycosylated and that protein glycosylation plays an important role in health and diseases. At present, simple, fast and inexpensive methods are sought for clinical applications and particularly for improved diagnostics of various diseases, including cancer. We propose a label-...

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, includi...

An extensive characterization of pristine and oxidized Ti3C2Tx (T: O, OH, F) MXene showed that exposure of MXene to an anodic potential in the aqueous solution oxidizes the nanomaterial forming TiO2 layer or TiO2 domains with subsequent TiO2 dissolution by F⁻ ions, making the resulting nanomaterial less electrochemically active compared to the pris...

In our study we used holocelluloses from sugar beet and bagasse for film preparation. Films from sugar beet holocellulose have better mechanical properties than from bagasse holocellulose. By subsequent carboxymethylation of bagasse holocellulose, films with better properties were produced. Specimens prepared from combined sugar beet and bagasse ca...

DOI: 10.1002/pmic.201500463 Mass spectrometry analysis of different linkages sialic acid is attached to the glycan backbone is a daunting task requiring derivatisation steps. In this work we applied lectins specifically recognizing either α-(2,3)- or α-(2,6)-linked terminal sialic acid for specific glycoprofiling of a prostate specific antigen (a p...

Impedimetric lectin biosensor for detection of changes in the glycan structure of antibodies isolated from human serum is here correlated with progression of rheumatoid arthritis (RA). The biosensor was built-up from a mixed self-assembled monolayer (SAM) on gold consisting of two different thiolated zwitterionic derivatives – carboxybetaine and su...

A simple fabrication method for preparation of surfaces able to switch from superhydrophobic to superhydrophilic state in a reversible and fast way is described. A self-assembled monolayer (SAM) consisting of quaternary ammonium group with aliphatic tail bearing terminal thiol functionality was created on gold nano/micro structured and gold planar...

The most attention, from all carbonaceous nanomaterials, is currently being paid to graphene-2D, one-atom-thick, highly ordered carbon sheets with excellent electrochemical, thermal, optical, and mechanical properties. From an application point of view, a good biocompatibility of graphene and its derivatives is highly appreciated and increasingly e...

The construction of a sensitive electrochemical lectin-based immunosensor for detection of a prostate specific antigen (PSA) is shown here. Three lectins with different carbohydrate specificities were used in this study to glycoprofile PSA, which is the most common biomarker for prostate cancer (PCa) diagnosis. The biosensor showed presence of α-L-...

A lot of strategies for smart approaches on surfaces were applied such as hydrogel layer, polymer brushes or self-assembly monolayers (SAM). [1] Nowadays switchable zwitterionic materials consisting of molecules with internally balanced charge between positive ammonium and negative carboxy group are promising candidates for this application. [2] Th...

Immobilization of glycans (complex carbohydrates) on surfaces is a tool on how to mimic exposure of glycans on proteins and cells to study their interaction with proteins, viral particlesg or human cells revealing details about pathological processes. Glycan biochips were successfully applied in such studies, but this technology requires presence o...

An ultrasensitive impedimetric glycan-based biosensor for reliable and selective detection of inactivated, but intact influenza viruses H3N2 was developed. Such glycan-based approach has a distinct advantage over antibody-based detection of influenza viruses since glycans are natural viral receptors with a possibility to selectively distinguish bet...

This study presents a proof-of-concept for the development of an impedimetric biosensor for ultra-sensitive glycoprofiling of prostate specific antigen (PSA). The biosensor exhibits three unique characteristics: (1) analysis of PSA with limit of detection (LOD) down to 4 aM; (2) analysis of the glycan part of PSA with LOD down to 4 aM level and; (3...

Impedimetric lectin biosensors capable of recognising two different carbohydrates (galactose and sialic acid) in glycans attached to antibodies isolated from human serum were prepared. The first step entailed the modification of a gold surface by a self-assembled monolayer (SAM) deposited from a solution containing a carboxybetaine-terminated thiol...

Impedimetric glycan biosensor with optimised glycan density was applied for detection of lectins and influenza hemagglutinins down to attomolar concentrations (aM).

Significant progress has been done in the electrochemical (EC) analysis of practically all proteins, based on the electroactivity of amino acid (aa) residues in proteins. From a transducer point of view, it can be anticipated that many different ways of how nanomaterials can be integrated into the EC detection platform of detection will be develope...

Gluconobacter oxydans bacteria exhibit a unique metabolism for quick and incomplete oxidation of a wide range of different compounds (aldoses, ketoses, mono- and poly-alcohols, etc.). Such biotransformation efficiency with simple biomass production led to the industrial applications of these bacteria in the production of several important commoditi...

Glycans and other saccharides attached to proteins and lipids, are involved in numerous physiological or pathological processes. The changes in glycosylation are usually associated with some pathological states (such as cancer), therefore these alterations are useful tools in diagnostics. This review gives basic insight into glycomics, describes th...

Saccharides play important roles in organisms. Changes in glycosylation and in structure of glycans can induce many diseases or can be induced by diseases. Glycan biochips and biosensors are novel techniques the main role of which is to study the glycan – protein interactions. In the construction of biochips and biosensors it is important to create...

In this mini-review the most advanced patterning protocols and transducing schemes for the development of ultrasensitive label-free and label-based lectin biosensors for the glycoprofiling of disease markers and some cancerous cells are described. The performance of such lectin biosensors with interfacial properties tuned to the nanoscale are criti...

Graphene-based nanomaterials have become the focus of attention in nanotechnology due to their unique properties. An exceptional charge transport mobility and thermal, optical and mechanical properties make them an interesting material in many applications including electrochemical biosensing. The aim of this review is to provide comprehensive info...

Glycan biochips and biosensors are potentially important tools for detection of glycan – protein interactions. Among several applications they can be used for rapid and precise diagnosis of various diseases and infections. Two major detection techniques available for construction of glycan biochips and biosensors – fluorescent labelled and label-fr...

We present here comparison of a build-up of two ultrasensitive lectin biosensors based on 2D or 3D architecture. A 2D lectin biosensor was prepared by a covalent immobilisation of lectin Sambucus nigra agglutinin (SNA) recognising sialic acid directly on a mixed self-assembled monolayer (SAM) on planar gold surfaces. A 3D biosensor was prepared...

This chapter would like to provide a short survey of the most promising concepts applied recently in analysis of glycoproteins based on lectins. The first part describes the most exciting analytical approaches used in the field of glycoprofiling based on integration of nanoparticles, nanowires, nanotubes, or nanochannels or using novel transducing...

We report on an ultrasensitive label-free lectin-based impedimetric biosensor for the determination of the sialylated glycoproteins fetuin and asialofetuin. A sialic acid binding agglutinin from Sambucus nigra I was covalently immobilised on a mixed self-assembled monolayer (SAM) consisting of 11-mercaptoundecanoic acid and 6-mercaptohexanol. Poly(...

Glycans and other saccharide moieties attached to proteins and lipids, or present on the surface of a cell, are actively involved in numerous physiological or pathological processes. Their structural flexibility (that is based on the formation of various kinds of linkages between saccharides) is making glycans superb "identity cards". In fact, glyc...

Ultrasensitive impedimetric lectin biosensors recognising different glycan entities on serum glycoproteins were constructed. Lectins were immobilised on novel mixed self-assembled monolayer containing 11-mercaptoundecanoic acid for covalent immobilisation of lectins and betaine terminated thiol to resist non-specific interactions. Construction of b...

We present here an ultrasensitive electrochemical biosensor based on a lectin biorecognition capable to detect concentrations of glycoproteins down to attomolar (aM) level by investigation of changes in the charge transfer resistance (Rct) using electrochemical impedance spectroscopy (EIS). On polycrystalline gold modified by an aminoalkanethiol li...