Publications by authors named "Kristina A Malsagova"

14 Publications

  • Page 1 of 1

Use of Silicon Nanowire Sensors for Early Cancer Diagnosis.

Molecules 2021 Jun 18;26(12). Epub 2021 Jun 18.

Institute of Biomedical Chemistry, 119121 Moscow, Russia.

The review covers some research conducted in the field of medical and biomedical application of devices based on silicon sensor elements (Si-NW-sensors). The use of Si-NW-sensors is one of the key methods used in a whole range of healthcare fields. Their biomedical use is among the most important ones as they offer opportunities for early diagnosis of oncological pathologies, for monitoring the prescribed therapy and for improving the people's quality of life.
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http://dx.doi.org/10.3390/molecules26123734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234636PMC
June 2021

Micro-Raman Characterization of Structural Features of High-k Stack Layer of SOI Nanowire Chip, Designed to Detect Circular RNA Associated with the Development of Glioma.

Molecules 2021 Jun 18;26(12). Epub 2021 Jun 18.

Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia.

The application of micro-Raman spectroscopy was used for characterization of structural features of the high-k stack (h-k) layer of "silicon-on-insulator" (SOI) nanowire (NW) chip (h-k-SOI-NW chip), including AlO and HfO in various combinations after heat treatment from 425 to 1000 °C. After that, the NW structures h-k-SOI-NW chip was created using gas plasma etching optical lithography. The stability of the signals from the monocrine phase of HfO was shown. Significant differences were found in the elastic stresses of the silicon layers for very thick (>200 nm) AlO layers. In the UV spectra of SOI layers of a silicon substrate with HfO, shoulders in the Raman spectrum were observed at 480-490 cm of single-phonon scattering. The h-k-SOI-NW chip created in this way has been used for the detection of DNA-oligonucleotide sequences (oDNA), that became a synthetic analog of circular RNA-circ-SHKBP1 associated with the development of glioma at a concentration of 1.1 × 10 M. The possibility of using such h-k-SOI NW chips for the detection of circ-SHKBP1 in blood plasma of patients diagnosed with neoplasm of uncertain nature of the brain and central nervous system was shown.
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http://dx.doi.org/10.3390/molecules26123715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234461PMC
June 2021

Molecular Portrait of an Athlete.

Diagnostics (Basel) 2021 Jun 15;11(6). Epub 2021 Jun 15.

Biobanking Group, Branch of Institute of Biomedical Chemistry "Scientific and Education Center", 109028 Moscow, Russia.

Sequencing of the human genome and further developments in "omics" technologies have opened up new possibilities in the study of molecular mechanisms underlying athletic performance. It is expected that molecular markers associated with the development and manifestation of physical qualities (speed, strength, endurance, agility, and flexibility) can be successfully used in the selection systems in sports. This includes the choice of sports specialization, optimization of the training process, and assessment of the current functional state of an athlete (such as overtraining). This review summarizes and analyzes the genomic, proteomic, and metabolomic studies conducted in the field of sports medicine.
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http://dx.doi.org/10.3390/diagnostics11061095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232626PMC
June 2021

Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols.

Nutrients 2021 May 12;13(5). Epub 2021 May 12.

Institute of Biomedical Chemistry, Group of Biobanking, 10 Pogodinskaya Str., Bld. 8, 119121 Moscow, Russia.

The way of plant sterols transformation and their benefits for humans is still a question under the massive continuing revision. In fact, there are no receptors for binding with sterols in mammalians. However, possible biotransformation to steroids that can be catalyzed by gastro-intestinal microflora, microbial cells in prebiotics or cytochromes system were repeatedly reported. Some products of sterols metabolization are capable to imitate resident human steroids and compete with them for the binding with corresponding receptors, thus affecting endocrine balance and entire physiology condition. There are also tremendous reports about the natural origination of mammalian steroid hormones in plants and corresponding receptors for their binding. Some investigations and reports warn about anabolic effect of sterols, however, there are many researchers who are reluctant to believe in and have strong opposing arguments. We encounter plant sterols everywhere: in food, in pharmacy, in cosmetics, but still know little about their diverse properties and, hence, their exact impact on our life. Most of our knowledge is limited to their cholesterol-lowering influence and protective effect against cardiovascular disease. However, the world of plant sterols is significantly wider if we consider the thousands of publications released over the past 10 years.
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http://dx.doi.org/10.3390/nu13051623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150896PMC
May 2021

Detection of Influenza Virus Using a SOI-Nanoribbon Chip, Based on an N-Type Field-Effect Transistor.

Biosensors (Basel) 2021 Apr 12;11(4). Epub 2021 Apr 12.

Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia.

The detection of influenza A virions with a nanoribbon detector (NR detector) has been demonstrated. Chips for the detector have been fabricated based on silicon-on-insulator nanoribbon structures (SOI nanoribbon chip), using a complementary metal-oxide-semiconductor (CMOS)-compatible technology-by means of gas-phase etching and standard optical photolithography. The surface of the SOI nanoribbon chip contains a matrix of 10 nanoribbon (NR) sensor elements. SOI nanoribbon chips of n-type conductance have been used for this study. For biospecific detection of target particles, antibodies against influenza virus have been covalently immobilized onto NRs. Influenza A virus detection was performed by real-time registration of the source-drain current through the NRs. The detection of the target viral particles was carried out in buffer solutions at the target particles concentration within the range from 10 to 10 viral particles per milliliter (VP/mL). The lowest detectable concentration of the target viral particles was 6 × 10 M (corresponding to 10 VP/mL). The use of solutions containing ~10 to 10 VP/mL resulted in saturation of the sensor surface with the target virions. In the saturation mode, detection was impossible.
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http://dx.doi.org/10.3390/bios11040119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069153PMC
April 2021

Raman Spectroscopy-Based Quality Control of "Silicon-On-Insulator" Nanowire Chips for the Detection of Brain Cancer-Associated MicroRNA in Plasma.

Sensors (Basel) 2021 Feb 13;21(4). Epub 2021 Feb 13.

Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia.

Application of micro-Raman spectroscopy for the monitoring of quality of nanowire sensor chips fabrication has been demonstrated. Nanowire chips have been fabricated on the basis of «silicon-on-insulator» (SOI) structures (SOI-NW chips). The fabrication of SOI-NW chips was performed by optical litography with gas-phase etching. The so-fabricated SOI-NW chips are intended for highly sensitive detection of brain cancer biomarkers in humans. In our present study, two series of experiments have been conducted. In the first experimental series, detection of a synthetic DNA oligonucleotide (oDNA) analogue of brain cancer-associated microRNA miRNA-363 in purified buffer solution has been performed in order to demonstrate the high detection sensitivity. The second experimental series has been performed in order to reveal miRNA-363 itself in real human plasma samples. To provide detection biospecificity, the SOI-NW chip surface was modified by covalent immobilization of probe oligonucleotides (oDNA probes) complementary to the target biomolecules. Using the SOI-NW sensor chips proposed herein, the concentration detection limit of the target biomolecules at the level of 3.3 × 10 M has been demonstrated. Thus, the approach employing the SOI-NW chips proposed herein represents an attractive tool in biomedical practice, aimed at the early revelation of oncological diseases in humans.
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http://dx.doi.org/10.3390/s21041333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918486PMC
February 2021

Optical Monitoring of the Production Quality of Si-Nanoribbon Chips Intended for the Detection of ASD-Associated Oligonucleotides.

Micromachines (Basel) 2021 Feb 3;12(2). Epub 2021 Feb 3.

Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia.

Gas-phase etching and optical lithography were employed for the fabrication of a silicon nanoribbon chip (Si-NR chip). The quality of the so-fabricated silicon nanoribbons (Si-NRs) was monitored by optical Raman scattering spectroscopy. It was demonstrated that the structures of the Si-NRs were virtually defect-free, meaning they could be used for highly sensitive detection of biological macromolecules. The Si-NR chips were then used for the highly sensitive nanoelectronics detection of DNA oligonucleotides (oDNAs), which represent synthetic analogs of 106a-5p microRNA (miR-106a-5p), associated with the development of autism spectrum disorders in children. The specificity of the analysis was attained by the sensitization of the Si-NR chip sur-face by covalent immobilization of oDNA probes, whose nucleotide sequence was complementary to the known sequence of miR-106a-5p. The use of the Si-NR chip was demonstrated to al-low for the rapid label-free real-time detection of oDNA at ultra-low (~10 M) concentrations.
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http://dx.doi.org/10.3390/mi12020147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913754PMC
February 2021

Mass Spectrometric Identification of Proteins Enhanced by the Atomic Force Microscopy Immobilization Surface.

Int J Mol Sci 2021 Jan 4;22(1). Epub 2021 Jan 4.

Institute of Biomedical Chemistry, 119121 Moscow, Russia.

An approach to highly-sensitive mass spectrometry detection of proteins after surface-enhanced concentrating has been elaborated. The approach is based on a combination of mass spectrometry and atomic force microscopy to detect target proteins. (1) Background: For this purpose, a technique for preliminary preparation of molecular relief surfaces formed as a result of a chemical or biospecific concentration of proteins from solution was developed and tested on several types of chip surfaces. (2) Methods: mass spectrometric identification of proteins using trailing detectors: ion trap, time of flight, orbital trap, and triple quadrupole. We used the electrospray type of ionization and matrix-assisted laser desorption/ionization. (3) Results: It is shown that when using locally functionalized atomically smooth surfaces, the sensitivity of the mass spectrometric method increases by two orders of magnitude as compared with measurements in solution. Conclusions: It has been demonstrated that the effective concentration of target proteins on specially prepared surfaces increases the concentration sensitivity of mass spectrometric detectors-time-of-flight, ion trap, triple quadrupole, and orbital ion trap in the concentration range from up to 10 M.
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http://dx.doi.org/10.3390/ijms22010431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795915PMC
January 2021

Highly Sensitive Detection of CA 125 Protein with the Use of an n-Type Nanowire Biosensor.

Biosensors (Basel) 2020 Dec 18;10(12). Epub 2020 Dec 18.

Laboratory of nanotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia.

The detection of CA 125 protein in a solution using a silicon-on-insulator (SOI)-nanowire biosensor with n-type chip has been experimentally demonstrated. The surface of nanowires was modified by covalent immobilization of antibodies against CA 125 in order to provide the biospecificity of the target protein detection. We have demonstrated that the biosensor signal, which results from the biospecific interaction between CA 125 and the covalently immobilized antibodies, increases with the increase in the protein concentration. At that, the minimum concentration, at which the target protein was detectable with the SOI-nanowire biosensor, amounted to 1.5 × 10 M.
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http://dx.doi.org/10.3390/bios10120210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766891PMC
December 2020

Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization.

Pharmaceutics 2020 Dec 19;12(12). Epub 2020 Dec 19.

Biobanking Group, Branch of Institute of Biomedical Chemistry "Scientific and Education Center", 109028 Moscow, Russia.

Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician's ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.
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http://dx.doi.org/10.3390/pharmaceutics12121240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765968PMC
December 2020

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development.

Molecules 2020 Jan 31;25(3). Epub 2020 Jan 31.

V.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia.

Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant ( < 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
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http://dx.doi.org/10.3390/molecules25030619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036866PMC
January 2020

Micro-Raman Spectroscopy for Monitoring of Deposition Quality of High-k Stack Protective Layer onto Nanowire FET Chips for Highly Sensitive miRNA Detection.

Biosensors (Basel) 2018 Jul 27;8(3). Epub 2018 Jul 27.

Institute of Biomedical Chemistry (IBMC), Moscow 119121, Russia.

Application of micro-Raman spectroscopy for the monitoring of quality of high-k (h-k) dielectric protective layer deposition onto the surface of a nanowire (NW) chip has been demonstrated. A NW chip based on silicon-on-insulator (SOI) structures, protected with a layer of high-k dielectric ((h-k)-SOI-NW chip), has been employed for highly sensitive detection of microRNA (miRNA) associated with oncological diseases. The protective dielectric included a 2-nm-thick Al₂O₃ surface layer and a 8-nm-thick HfO₂ layer, deposited onto a silicon SOI-NW chip. Such a chip had increased time stability upon operation in solution, as compared with an unprotected SOI-NW chip with native oxide. The (h-k)-SOI-NW biosensor has been employed for the detection of DNA oligonucleotide (oDNA), which is a synthetic analogue of miRNA-21 associated with oncological diseases. To provide biospecificity of the detection, the surface of (h-k)-SOI-NW chip was modified with oligonucleotide probe molecules (oDVA probes) complementary to the sequence of the target biomolecule. Concentration sensitivity of the (h-k)-SOI-NW biosensor at the level of ~10 M has been demonstrated.
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http://dx.doi.org/10.3390/bios8030072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164057PMC
July 2018

Highly sensitive protein detection by biospecific AFM-based fishing with pulsed electrical stimulation.

FEBS Open Bio 2017 08 10;7(8):1186-1195. Epub 2017 Jul 10.

Institute of Biomedical Chemistry Moscow Russia.

We report here the highly sensitive detection of protein in solution at concentrations from 10 to 10 m using the combination of atomic force microscopy (AFM) and mass spectrometry. Biospecific detection of biotinylated bovine serum albumin was carried out by fishing out the protein onto the surface of AFM chips with immobilized avidin, which determined the specificity of the analysis. Electrical stimulation was applied to enhance the fishing efficiency. A high sensitivity of detection was achieved by application of nanosecond electric pulses to highly oriented pyrolytic graphite placed under the AFM chip. A peristaltic pump-based flow system, which is widely used in routine bioanalytical assays, was employed throughout the analysis. These results hold promise for the development of highly sensitive protein detection methods using nanosensor devices.
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http://dx.doi.org/10.1002/2211-5463.12253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537060PMC
August 2017

SOI nanowire for the high-sensitive detection of HBsAg and α-fetoprotein.

Lab Chip 2012 Dec;12(23):5104-11

Institute of Biomedical Chemistry RAMS, Russia, Moscow.

Silicon-on-isolator-nanowires (SOI-NWs) were used for the label-free, real-time biospecific detection of the hepatitis B marker HBsAg and cancer marker α-fetoprotein (AFP). Specific protein-protein recognition was carried out using individual NWs that were functionalized with antibodies. To solve the problem of non-specific binding of target protein molecules to the sensor element the use of a reference NW with immobilized antibodies against non-target proteins was proposed. Using individual SOI-NW surface functionalization allowed the fabrication of a NW array, containing working NWs and reference NWs within one chip. It was shown that this approach allows us to reach a detection limit up to 10(-14) and 10(-15) M for HBsAg and AFP, respectively. Our investigations also allowed us to reveal the influence of the charged state of the target protein molecules and antibodies in solutions with various pH values on the target protein detection limit. A high sensitivity NW-detector is of interest for the creation of diagnosticums for hepatitis B and for the early stages of cancer diseases.
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http://dx.doi.org/10.1039/c2lc40555eDOI Listing
December 2012
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