Aliya Bekmurzayeva

Tuberculosis diagnosis using immunodominant, secreted antigens of Mycobacterium tuberculosis

Tuberculosis (TB) remains a major public health concern in most low-income countries. Hence, rapid and sensitive TB diagnostics play an important role in detecting and preventing the disease. In addition to established diagnostic methods, several new approaches have been reported. Some techniques are simple but time-consuming, while others require complex instrumentation. One prominent and readily available approach is to detect proteins that Mycobacterium tuberculosis secretes, such as Mpt64, the 6-kDa early secreted antigenic target (Esat6), the 10-kDa culture filtrate protein (Cfp10), and the antigen 85 (Ag85) complex. Although their functions are not fully understood, a growing body of molecular evidence implicates them in M. tuberculosis virulence. Currently these biomarkers are either being used or investigated for use in skin patch tests, biosensor analyses, and immunochromatographic, immunohistochemical, polymerase chain reaction-based, and enzyme-linked immunosorbent assays. This review provides a comprehensive discussion of the roles these immunodominant antigens play in M. tuberculosis pathogenesis and compares diagnostic methods based on the detection of these proteins with more established tests for TB.

Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer

The Bcl proteins play a critical role in apoptosis, as mutations in family members interfere with normal programmed cell death. Such events can cause cell transformation, potentially leading to cancer. Recent discoveries indicate that some viral proteins interfere with Bcl proteins either directly or indirectly; however, these data have not been systematically described. Some viruses encode proteins that reprogramme host cellular signalling pathways controlling cell differentiation, proliferation, genomic integrity, cell death, and immune system recognition. This review analyses and summarises the existing data and discusses how viral proteins interfere with normal pro- and anti-apoptotic functions of Bcl-2 and Bcl-xL. Particularly, this article focuses on how viral proteins, such as Herpesviruses, HTLV-1, HPV and HCV, block apoptosis and how accumulation of such interference predisposes cancer development. Finally, we discuss possible ways to prevent and treat cancers using a combination of traditional therapies and antiviral preparations that are effective against these viruses.

Detection of tilted fiber Bragg grating fiber-optic sensors with short-term KLT: towards low-cost biosensors

Tilted Fiber Bragg Grating (TFBG) optical fiber sensors can be employed as refractive index sensors, and functionalized as biosensors. The TFBG cladding modes exhibit a small yet detectable sensitivity to the refractive index in the surrounding of the sensing region. One of the weaknesses of TFBG is that classical interrogation methods require narrow wavelength resolution to analyze these spectral features which can be achieved only through a bulky setup. In this work, we propose a demodulation method, namely the short term Karhunen-Loeve Transform (ST-KLT) that can be applied to a low-cost spectrometer that detects the TFBG reflection spectrum. The method is capable of detecting refractive index variations in the order of 10-3 - 10-4 refractive index units (RIU), and is a potential pillar towards low-cost TFBG biosensors.

Detection of various Thrombin concentrations using etched fiber Bragg gratings functionalized with DNA aptamer

The response of etched fiber Bragg grating (EFBG) functionalized with 29-mer DNA aptamer to the different concentrations of Thrombin protein has been investigated. Etched FBGs are an efficient technology for detection of refractive index, and have been demonstrated also for biosensors applications. EFBGs have a simpler manufacturing approach comparing to other methodologies and are based on a low-cost device; their fabrication can be achieved by simple chemical etching, without requiring fusion splicing. During the test we assessed its feasibility for small variations of thrombin concentrations (10μg/ml, 20μg/ml, 40μg/ml and 80μg/ml). In particular, we performed experiments of chemical etching with hydrofluoric acid, which progressively depletes the fiber cladding exposing the core to the outer medium. Additionally, unstriped not etched FBGs were also used as a control for temperature pattern compensation. Before functionalization, EFBG was calibrated with different sucrose and ethanol solutions that validated the sensitivity to refractive index change. EFBG was further silanized with 3-Aminopropyl-triethoxysilane (APTES) in order to immobilize Thrombin binding aptamer on the silica surface of the fiber. The change of Bragg wavelength when functionalized EFBG is exposed to different concentrations of Thrombin using Micron Optics Hyperion si255-x55 sensing system was demonstrated. A small yet detectable sensitivity (several tens of nanomolars) even between small protein variations allows hypothesizing a future use of this kind of functionalized fiber for biosensor development.

An etched chirped fiber Bragg grating for measurement of refractive index and temperature pattern

In this work, partially etched chirped fiber Bragg grating (pECFBG) for the real-time multi-parameter measurement of temperature and refractive index is proposed. The sensor is fabricated by wet-etching a portion of a linearly chirped FBG with linear chirp profile. Obtained CFBG has two active areas: the unetched part of the grating that can be used either as a uniform temperature sensor, or to detect thermal gradients experienced through the grating length; the etched part, besides having a similar thermal sensitivity, is exposed to refractive index sensing through the variations of external refractive index. Overall, the pECFBG structure behaves as a compact sensor with multi-parameter capability, that can both measure temperature and refractive index on the same grating, but also spatially resolve temperature detection through the grating section. The results have been validated through both a model and experimental setup, showing that the mutual correlation algorithm applied to different spectral parts of the grating is able to discriminate between uniform and gradient-shaped temperature profiles, and refractive index changes. The reflected spectra showed a clear correlation between the RI change of the surrounding media and spectral shift with temperature variations.

Partially etched chirped fiber Bragg grating (pECFBG) for joint temperature, thermal profile, and refractive index detection

In this work, a partially etched chirped fiber Bragg grating (pECFBG) is introduced, as a compact sensor for multi-parametric measurement of temperature, thermal gradients over the active length, and refractive index. The sensor is fabricated by wet-etching a portion of a 14-mm linearly chirped FBG with linear chirp profile. The resulting device has two active areas: the unetched part of the grating (2 mm) can be used either as a uniform temperature sensor, or to detect thermal gradients experienced through the grating length by means of a spectral reconstruction technique; the etched part (12 mm), besides having a similar thermal sensitivity, is exposed to refractive index sensing through the introduction of a sensitivity to external refractive index. Overall, the pECFBG structure behaves as a compact sensor with multi-parameter capability, that can both measure temperature and refractive index on the same grating, but also spatially resolve temperature detection through the grating section. The results have been validated through both a model and experimental setup, showing that the mutual correlation algorithm applied to different spectral parts of the grating is able to discriminate between uniform and gradient-shaped temperature profiles, and refractive index changes.

Surface modification of stainless steel for biomedical applications: Revisiting a century-old material

Stainless steel (SS) has been widely used as a material for fabricating cardiovascular stents/valves, orthopedic prosthesis, and other devices and implants used in biomedicine due to its malleability and resistance to corrosion and fatigue. Despite its good mechanical properties, SS (as other metals) lacks biofunctionality. To be successfully used as a biomaterial, SS must be made resistant to the biological environment by increasing its anti-fouling properties, preventing biofilm formation (passive surface modification), and imparting functionality for eluting a specific drug or capturing selected cells (active surface modification); these features depend on the final application. Various physico-chemical techniques, including plasma vapor deposition, electrochemical treatment, and attachment of different linkers that add functional groups, are used to obtain SS with increased corrosion resistance, improved osseointegration capabilities, added hemocompatibility, and enhanced antibacterial properties. Existing literature on this topic is extensive and has not been covered in an integrated way in previous reviews. This review aims to fill this gap, by surveying the literature on SS surface modification methods, as well as modification routes tailored for specific biomedical applications. STATEMENT OF SIGNIFICANCE Stainless steel (SS) is widely used in many biomedical applications including bone implants and cardiovascular stents due to its good mechanical properties, biocompatibility and low price. Surface modification allows improving its characteristics without compromising its important bulk properties. SS with improved blood compatibility (blood contacting implants), enhanced ability to resist bacterial infection (long-term devices), better integration with a tissue (bone implants) are examples of successful SS surface modifications. Existing literature on this topic is extensive and has not been covered in an integrated way in previous reviews. This review paper aims to fill this gap, by surveying the literature on SS surface modification methods, as well as to provide guidance for selecting appropriate modification routes tailored for specific biomedical applications.

Wavelet analysis of multi-mode behavior of an etched Fiber Bragg Grating Sensor operating in sucrose solutions

Fiber optic sensors represent an attractive alternative in chemical, bio-chemical and medical applications. Their success can be retrieved in their peculiar properties such as: electromagnetic interference immunity, fast response, high sensitivity, and small size. In this context, Fiber Bragg Gratings (FBGs) play a key role in applications like measurements of temperature and strain. The mechanism of FBGs is related to the dependence between the characteristic wavelength reflected by the FBG and the effective index of the modes propagating inside the fibers. This property can be exploited to engineer a new and inexpensive class of FBG devices for measuring refractive index of solutions. By reducing the cladding thickness of the single mode fiber, where the FBG is inscribed, the structure becomes three layers and the modes guidance properties become more and more dependent on the external environment, including the refractive index of the solution to measure. In this work, an FBG has been etched by a solution of HF acid and immersed in different solutions of water and sucrose. Results show a strong multi-modal behavior induced by the guidance properties of the three-layer system. The reflected spectra, characterized by a large band whose width, are strictly dependent on the sucrose concentration in solution. As the sucrose increases, the refractive index of the solution increases. The bandwidth reduces, showing a wavelength shift toward longer wavelength. While the wavelength shift is not so relevant the variation of the bandwidth is significant, suggesting an effective interrogation method based on wavelet signal processing.

Interrogation of coarsely sampled Tilted Fiber Bragg Grating (TFBG) sensors with KLT

Tilted fiber Bragg gratings (TFBG) can be used as refractive index sensors, as their cladding modes, amplitude, and wavelength changes with the outer refractive index. However, as cladding modes have bandwidths that are narrower than the resolution of most infrared spectrometers, they can be detected only with an optical spectrum or vector analyzers. In this work, we demonstrate that through ad hoc implementation, the Karhunen-Loeve transform (KLT) algorithm can be used to demodulate a TFBG even using a coarse interrogator (156 pm), whereas cladding modes cannot be discriminated in the TFBG spectrum. We observe that the KLT output results are a reliable indicator to detect refractive index changes up to 1.85 ⋅ 10−3 refractive index units (RIU), down to a resolution of ~10−5 RIU. The KLT can be used to demodulate TFBG sensors and biosensors operating in small refractive index change conditions.