Modares Journal of Biotechnology

Abstract Microfluidic technology, known as the study and manipulation of fluid flow in channels with micrometer-scale dimensions, is one of the most important achievements in recent decades in the field of miniaturization technologies. By integrating knowledge from engineering, physics, chemistry, and biology, this technology enables the precise control and analysis of very small volumes of liquids, where fluid behavior at this scale differs significantly from the macro scale. Key features of microfluidics include precise control of physical parameters, reduced consumption of samples and reagents, faster experimentation, and the ability to perform multiple processes simultaneously. These advantages have led to the development of devices known as “lab-on-a-chip,” which can carry out complex biological processes in small, portable formats. In recent years, this technology has gained a prominent position in various fields of biotechnology and medicine. Its notable applications include rapid disease diagnosis, genetic analysis, drug screening, targeted drug delivery, and modeling of human tissues and organs. Moreover, advances in polymeric chips and paper-based microfluidics have further expanded the potential applications of this technology. The aim of this article is to provide a comprehensive review of microfluidic technology applications in biotechnology and to examine the most significant advancements, challenges, and future perspectives in three areas: pharmaceuticals, diagnostics, and bioengineering.

Abstract Interleukin-6 (IL-6) is a key cytokine with dual pro- and anti-inflammatory roles, critically involved in immune regulation, cell differentiation, and tissue injury. Elevated serum levels of IL-6 serve as an indicator of various pathological conditions, including chronic infections, cancer, autoimmune diseases, and Alzheimer’s disease. Despite advances in ELISA-based assays, these methods remain costly, time-consuming, and require relatively large sample volumes.
In this study, a novel omniphobic biosensor inspired by biological structures was developed for the sensitive detection of IL-6. Anti-IL-6 antibodies were uniformly immobilized using spray-coating onto a fluorosilane-treated polymethyl methacrylate (PMMA) substrate. To enhance stability and minimize nonspecific adsorption, a layer of biocompatible lubricating liquid was introduced onto the sensor surface.
The fabricated biosensor demonstrated exceptional sensitivity, detecting IL-6 at concentrations as low as 2.5 pg/mL, even in human whole blood samples. Its high specificity, wide linear response range, and excellent reproducibility make this platform a promising candidate for rapid and sensitive detection of inflammatory biomarkers.

Abstract Mesenchymal stem cells (MSCs) are among the most widely used types of adult stem cells in studies related to tissue engineering, cell therapy, and regenerative medicine. Ensuring the appropriate conditions and medium for the proliferation of these cells, as well as guiding their differentiation towards target cells, particularly for tissues with limited self-repair capabilities (e.g., neural cells), has been a focus in numerous studies. In the present study, the proliferative and differnetiative behavior of MSCs derived from the bone marrow of mice was examined in proximity to a collagen hydrogel and different concentrations of hippocampal extract obtained from fetal mouse brain tissue. Results from cellular assays, including the MTT test, confirmed the high biocompatibility of collagen hydrogel and the positive effect of hippocampal extract on cell growth. The expression levels of proteins such as nestin and GFAP, as well as fluorescence microscopy images, indicated that the presence of hippocampal extract along with collagen hydrogel not only promotes the formation of neural progenitor cells, but also encourages these cells to retain their stemness and enhances their growth and proliferation. Overall, it appears that collagen hydrogel and the neurotrophic effects of hippocampal extract can create suitable conditions for the production of neural progenitor cells.

Abstract Mnemiopsin 2 is a Ca2+ regulated photo protein with 207 residues and a molecular weight of 24722 Daltons. In the structure of this photoprotein, the EF-hand I-III-IV motifs have retained their function in binding to Ca2+, while the EF-hand II has lost its activity during evolution. Each EF-hand has a helix-loop-helix (HLH) structure. Loops with length of 12 residues are responsible for Ca2+ binding. In this study, in order to recovery the structural and functional of the EF-hand loop II, a Photoprotein Mnemiopsin Chimeric (PMC) was designed using direct evolution and rational design. The mutant structure were modeled by Modeller v2.10 software. Then the best model was evaluated using the Chimera x.8.1 software and Modeval and SAVES and ModEval server for RMSD, RRDistance, Z-Dope, Errat and Verify 3D parameters were investigated. Also, the secondary structure, free energy of folding and accessible surface of the models were investigated by the VADAR server. The hydrophobicity and instability index were evaluated by Protscale and ProtParam servers. The Prosite results indicate the formation of EF-hand II loop in PMC. It is worth mentioning that Changes in the surface hydrophobicity of the recovered EF-hand II motif may affect the interaction with Ca2+. That means, due to the increase the Ca2+ binding sites, sensitivity to Ca2+ and activity were predicted to change.
 

Abstract Objectives: Methanotrophs are microorganisms that utilize methane as a carbon and energy source, playing a crucial role in the carbon cycle. Due to their high potential for single-cell protein (SCP) production, they are considered valuable candidates in biotechnological industries. This study aimed to investigate the enhancement of biomass production under aerobic and anaerobic methane conditions for three methanotrophic species-Methylococcus capsulatus (Bath), Methylomicrobium album BG8, and Methanoperedens nitroreducens-using in silico approach.
Materials and Methods: The genome-scale metabolic models of these microorganisms (iMcBath, iJV803, and iMN22HE) were reconstructed and analyzed using the COBRA Toolbox in the MATLAB environment. Target reactions for optimization were selected based on flux sensitivity analysis and a comprehensive literature review identifying key reactions in methane oxidation and nitrogen metabolism. Subsequently, Flux Balance Analysis (FBA) was performed to evaluate biomass flux under baseline and optimized conditions, and the results were comparatively assessed.
Results: After the applied metabolic modifications, the biomass flux of M. capsulatus, M. album, and M. nitroreducens increased by 2.28, 1.94, and 1.25-fold compared to their baseline states, respectively. Moreover, flux sensitivity and variability analyses indicated that the model predictions were robust against changes in substrate uptake rates.
Conclusion: Given the substantial increase in biomass yield of Methylococcus capsulatus (Bath), along with its established biotechnological relevance and available cultivation technology, it is recommended that the proposed metabolic modifications be experimentally validated to expand its potential industrial and bioprocess applications.

Abstract Fruite juices were already under intensive analytical authenticity control for decades. Adulteration is releativly easy to perform because of the chemical composition and the wide natural variation seen in juice. Addition of water and/or sugar, acidification, cheaper fruit, colorants, flavor, and vitamins are typically frauds that are performed with criminal intent and sometimes with high level sophistication to make the adulterated products as difficult as possible to detect. In this sense, effective, reliable and rapid food authentication methods represent a valuable and irreplaceable tool for the authorities to set up control systems to ensure juice quality and safety and to promote mitigation of fraud. D-Isocitric acid and citric acid are two organic acid found in most fruit juices.  They are an important marker in multicomponent procedures for the evaluation of authenticity and quality of fruit products; high citric/isocitric acid ratios can be used as an indicator of citric acid addition in some juices especially in lime juice. The measurement of D-Isocitric acid by HPLC method is very difficult and time consuming in addition in this time, enzymatic method is one of the main international standard method for this component. One of the main aim in this research set up enzymatic method for measurement of these organic acids as one of the most commonly used analytical techniques (enzymatic method) and it represents a very attractive choice because this method is simple, rapid and cost effective.
 

Abstract Ferrite nanoparticles showed an important role in enhancing magnetic resonance imaging (MRI) image contrast because of their unique magnetic properties and potential to modulate water proton relaxation times. Their super-paramagnetic characterizations and biocompatibility provide high-sensitivity and high-precision imaging. In our study, cobalt ferrite nanoparticles were synthesized using the hydrothermal method and the structure and their characterizations were investigated. following phantom preparation, their effects on T₁ and T₂ in MRI were estimated. Elemental analysis (EDX) indicated that the nanoparticles comprised O (56.47%), Fe (27.89%), and Co (15.67%). The mean particle diameter was approximately 152 nm. FTIR spectroscopy revealed characteristic Fe–O and Co–O vibrational bands at 402.1 cm⁻¹ and 588.02 cm⁻¹, respectively, confirming the spinel crystal structure. UV-vis spectra showed metal-oxygen charge transfer 288 nm and d-d transitions (410, 495 nm), verifying the electronic properties. XRD analysis also presented pure spinel phase with characteristic (311), (400), and (440) peaks at 35.5°, 43.1°, and 62.76° (JCPDS 22-1086). This nanoparticle displayed a saturation magnetization of 28.18 emu/g and outstanding relaxivities (r₁ = 341.84, r₂ = 2367.3 mM⁻¹s⁻¹), validating a dual-contrast capability for both T₁ (positive) and T₂ (negative) weighted MRI imaging.

Abstract     Echium amoenum is a member of the Boraginaceae family, which has very valuable medicinal properties that are highly regarded in traditional Iranian medicine. Because different plant species Echium inappropriate harvesting of natural areas by humans, and the growing threat of biotic and abiotic stresses following the work resulted in reduced genetic diversity of a species is, a species of genetically keep reserves Curb upper's. Using seed cryopreservation, as one of the Ex situ plant germplasm conservation method we can store seed for long-term, with much lower expenses and without losing seed viability. In order to preserve E. amoenum seed under -196 ºC condition, three pre cryopreservation treatments, PVS2 solution, Desiccation and Glycerol were applied. The treated seeds were transferred into Liquid Nitrogen (LN) and stored for 1 week. In this study the effect of cryopreservation on germination and growth indices (germination percent, germination rate of plant species (E. amoenum) in storage conditions of cryopreservation (-196ºC) were evaluated for 1 week. Comparing treatments, significant differences were observed on germination percent and germination rate. The best treatment was desiccation. The results showed that, the long-term preservation of the species, seed in -196 ºC is possible.