Topological Darkness: How to Design a Metamaterial for Optical Biosensing with Virtually Unlimited Sensitivity

Due to the absence of labels and fast analyses, optical biosensors promise major advances in biomedical diagnostics, security, environmental and food safety applications. However, sensitivity of the most advanced plasmonic biosensor implementations has a fundamental limitation caused by losses in the system and or geometry of biochips. Here, we report a scissor effect in topologically dark metamaterials which is capable of providing virtually unlimited bona fide sensitivity to biosensing thus solving the bottleneck sensitivity limitation problem. We explain how the scissor effect can be realized via a proper design of topologically dark metamaterials and describe strategies for their fabrication. To validate the applicability of this effect in biosensing, we demonstrate the detection of folic acid (vitamin important for human health) in the wide 3-log linear dynamic range with the limit of detection of 0.125 nM, which is orders of magnitude better than previously reported for all optical counterparts. Our work opens possibilities for designing and realising plasmonic, semiconductor and dielectric metamaterials with ultra-sensitivity to binding events.Comment: 22 pages, 4 figure

Modelling of the receptor-ligand interaction in a single cell mode

Membrane-associated intrareceptoral and ligand-receptor interactions are involved in intracellular signalling. Community of surface receptors represents extremely important target for modern therapeutics. Their developing evidently requires elaboration of effective screening platforms. In this study we suggest universal platform designed to test receptor-ligand interaction in a "single cell" mode. For this purpose we created a DNA vector utilizing modular structure of chimeric receptors. The whole platform was tested using myc peptide - anti-myc antibody counterpart, which is directly linked with regulation of cancer cell development. In this study we succeeded to obtain Jurkat cells transduced with cDNA coding for chimeric antigenic receptor containing extracellular scFv of the myc-specific antibody and human Fc fused with transmembrane anchor. We showed that chimeric receptor interacts with myc peptide in a "single cell" mode, which in turn leads to the activation of T cells. We further suggest that designed system can be used for any other receptor-ligand pair to detect their interaction directly on the cell surface. Elaborated platform may be applied for the widerange screening of the agents with therapeutic potential on the cell membrane ex vivo

Force spectroscopy of barnase-barstar single molecule interaction

Results of the single molecule force spectroscopy study of specific interactions between ribonuclease barnase and its inhibitor barstar are presented. Experimental data obtained for the force loading rate ranging 2-70 nN/s are well approximated by a single straight line, from which the dissociation barrier of the width of 0.12 nm and height of 0.75-0.85X10(-19) J can be inferred. The measured value of specific interaction does not depend on the NaCl concentration. This apparently contradicts the well-known dependence of the binding energy of this pair on the salt concentration, but such a "contradiction" is explained by the insensitivity of the force spectroscopy data to the relatively long-range electrostatic interaction. The latter essentially contributes to the value of barnase-barstar binding energy revealed by biochemical measurements, and it is exactly this electrostatic interaction which is influenced by the salt concentration. Copyright (C) 2010 John Wiley & Sons, Ltd

Possibilities of radionuclide visualization of HER2/neu-positive breast cancer using a radiopharmaceutical based on recombinant targeting molecules DARPin9_29

Epidermal growth receptor HER2/neu is still of great interest, the overexpression of which is most often observed in patients with breast cancer and accounts for 15–20 % of cases. Present methods of HER2/neu determination have a number of significant drawbacks. In recent years, alternative framework proteins are used for the targeted radionuclide imaging. Molecules of DARPin (Design Ankyrin Repeat Protein) are one of representatives of scaffolds. Material and methods. The study included 4 breast cancer patients (T1-2N0-1M0) who were not receiving systemic therapy at the time of the study: in 2 patients, HER2/neu overexpression was noted, in 2 patients – not detected. HER2/neu status was determined using an immunohistochemical method and a FISH assay. At the preclinical stage, radiopharmaceutical 99mTc-DARPin9_29 was injected intravenously to all patients, «WholeBody» scintigraphy and single-photon emission computed tomography were performed 2 hours after injection. Results. The distribution of radiopharmaceuticals in organs 2 hours after injection revealed the greatest accumulation in the liver and kidneys. In studying of tumor/background indicator it was revealed that values of the studied parameter in patients with overexpression of HER2 receptors are more than 3 times higher than the values in the subgroup of patients with negative expression of this marker. Conclusion. According to the results of preliminary studies, the 99mTc-DARPin9_29 demonstrated significant differences between tumors with and without HER2/neu overexpression

Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement

The identification of low-frequency antigen-specific CD4+ T cells is crucial for effective immunomonitoring across various diseases. However, this task still encounters experimental challenges necessitating the implementation of enrichment procedures. While existing antigen-specific expansion technologies predominantly concentrate on the enrichment of CD8+ T cells, advancements in methods targeting CD4+ T cells have been limited. In this study, we report a technique that harnesses antigen-presenting extracellular vesicles (EVs) for stimulation and expansion of antigen-specific CD4+ T cells. EVs are derived from a genetically modified HeLa cell line designed to emulate professional antigen-presenting cells (APCs) by expressing key costimulatory molecules CD80 and specific peptide–MHC-II complexes (pMHCs). Our results demonstrate the beneficial potent stimulatory capacity of EVs in activating both immortalized and isolated human CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Our technique successfully expands low-frequency influenza-specific CD4+ T cells from healthy individuals. In summary, the elaborated methodology represents a streamlined and efficient approach for the detection and expansion of antigen-specific CD4+ T cells, presenting a valuable alternative to existing antigen-specific T-cell expansion protocols

Новые данные о согласованности результатов кожного аллерготестирования к пищевым аллергенам с уровнем специфического иммуноглобулина Е и симптомами пищевой аллергии у детей в эндемичных по описторхозу очагах

Aim: to investigate the consistency of skin prick-tests results with specific IgE level and symptoms of food allergy. The criteria of food allergy in children of opisthorchiasis endemic areas were developed: symptoms of food allergy within 2 hours, skin pricktests weal size ≥1 mm and (or) specific IgE ≥0,35 kUA/l.Представлен анализ согласованности результатов кожного аллерготестирования к пищевым аллергенам с оценкой уровня специфического иммуноглобулина Е (IgE) и симптомами пищевой аллергии у детей. На основании результатов эпидемиологического исследования предложены следующие критерии диагноза пищевой аллергии у детей, проживающих в регионах с высокой распространенностью описторхоза: наличие клинических симптомов, возникающих в течение 2 ч после употребления продукта питания, положительные результаты кожного аллерготестирования — средний диаметр папулы не менее 1 мм и (или) повышение уровня специфического IgE сыворотки крови не менее 0,35 кЕдА/л

Информационное обеспечение мониторинга степени тяжести и хронизации заболеваний у детей из отдаленных районов Томской области

The unified modeling language is used to design a structurally functional model of an information-analytical system for assessment of the state of a disease for the early detection of children with the increased risk of serious states living at sparsely populated territories. Using this model and methods of structured programming, as well as client-server technologies along with a structured query language, it is possible to develop a territorially distributed on-line system, which uses a common information space and accumulates centrally data on the severity of a disease.С помощью унифицированного языка моделирования спроектирована структурно-функциональная модель информационно-аналитической системы оценки состояния болезни с целью раннего выявления детей с повышенным риском развития тяжелых состояний, проживающих на территориях с малой плотностью населения. Основываясь на данной модели и методах структурного программирования, клиент-серверные технологии совместно с языком структурированных запросов позволяют реализовать в реальном времени территориально распределенную систему, используя единое информационное пространство, централизованно накапливать данные о тяжести течения болезни

Tunable Growth Factor Delivery from Injectable Hydrogels for Tissue Engineering

Current sustained delivery strategies of protein therapeutics are limited by the fragility of the protein, resulting in minimal quantities of bioactive protein delivered. In order to achieve prolonged release of bioactive protein, an affinity-based approach was designed which exploits the specific binding of the Src homology 3 (SH3) domain with short proline-rich peptides. Specifically, methyl cellulose was modified with SH3-binding peptides (MC-peptide) with either a weak affinity or strong affinity for SH3. The release profile of SH3-rhFGF2 fusion protein from hyaluronan MC-SH3 peptide (HAMC-peptide) hydrogels was investigated and compared to unmodified controls. SH3-rhFGF2 release from HAMC-peptide was extended to 10 days using peptides with different binding affinities compared to the 48 h release from unmodified HAMC. This system is capable of delivering additional proteins with tunable rates of release, while maintaining bioactivity, and thus is broadly applicable

Территориально распределенная система диспансерного наблюдения и мониторинга состояния здоровья детей с неврологическими расстройствами, проживающих в отдаленных районах Томской области

A unified simulation language has been used to develop the structurally functional model of the territorially distributed information system for follow-up care and monitoring of the health status of children with neurological disorders living in remote areas of the Tomsk Region. With this model and structured programming methods, client-server technologies along with the structured query language allow the development of the on-line information-analytical system, which uses the common information space and accumulates data on children with neurological disorders.С помощью унифицированного языка моделирования спроектирована структурно функциональная модель территориально распределенной информационно системы диспансерного наблюдения и мониторинга состояния здоровья детей с неврологическими расстройствами, проживающих в отдаленных районах Томской области. Основываясь на данной модели и применяя методы структурного программирования, клиент-серверные технологии совместно с языком структурированных запросов позволяют реализовать информационно-аналитическую систему, в «реальном времени» используя единое информационное пространство, централизованно накапливать данные о детях с неврологическими расстройствами