Sharif Digital Repository

Polymerase chain reaction (PCR) is a powerful tool for nucleic acid amplification and quantification. However, long thermocycling time is a major limitation of the commercial PCR devices in the point-of-care (POC). Herein, we have developed a rapid droplet-based photonic PCR (dpPCR) system, including a gold (Au) nanofilm-based microfluidic chip and a plasmonic photothermal cycler. The chip is fabricated by adding mineral oil to uncured polydimethylsiloxane (PDMS) to suppress droplet evaporation in PDMS microfluidic chips during PCR thermocycling. A PDMS to gold bonding technique using a double-sided adhesive tape is applied to enhance the bonding strength between the oil-added PDMS and the... 

Achieving high efficiency and throughput in droplet-based mixing over a small characteristic length, such as microfluidic channels, is one of the crucial parameters in Lab-on-a-Chip (LOC) applications. One solution to achieve efficient mixing is to use active mixers in which an external power source is utilized to mix two fluids. One of these active methods is magnetic micromixers using ferrofluid. In this technique, magnetic nanoparticles are used to make one phase responsive to magnetic force, and then by applying a magnetic field, two fluid phases, one of which is magneto-responsive, will sufficiently mix. In this study, we investigated the effect of the magnetic field’s characteristics... 

Droplet-based microfluidics is an attractive approach for producing microgels due to its high potential to control the size and shape of the particles and precisely entrap the substances within the hydrogel matrix. However, the microfluidic generation of monodisperse microgels with desired structures is still challenging. Indeed, the rheological and interfacial properties of the immiscible fluids, as well as the adopted gelling strategy, play important roles in microfluidic methods. Herein, sodium alginate droplets with different concentrations are generated via a microfluidic device with a flow-focusing unit. Besides, a combined in situ and ex situ strategy is optimized to crosslink sodium... 

Since plasma is rich in many biomarkers used in clinical diagnostic experiments, microscale blood plasma separation is a primitive step in most of microfluidic analytical chips. In this paper, a passive microfluidic device for on-chip blood plasma separation based on Zweifach–Fung effect and plasma skimming was designed and fabricated by hot embossing of microchannels on a PMMA substrate and thermal bonding process. Human blood was diluted in various times and injected into the device. The main novelty of the proposed microfluidic device is the design of diffuser-shaped daughter channels. Our results demonstrated that this design exerted a considerable positive influence on the separation... 

Since plasma is rich in many biomarkers used in clinical diagnostic experiments, microscale blood plasma separation is a primitive step in most of microfluidic analytical chips. In this paper, a passive microfluidic device for on-chip blood plasma separation based on Zweifach–Fung effect and plasma skimming was designed and fabricated by hot embossing of microchannels on a PMMA substrate and thermal bonding process. Human blood was diluted in various times and injected into the device. The main novelty of the proposed microfluidic device is the design of diffuser-shaped daughter channels. Our results demonstrated that this design exerted a considerable positive influence on the separation... 

Miniaturized systems based on the principles of microfluidics are widely used in various fields, such as biochemical and biomedical applications. Systematic design processes are demanded the proper use of these microfluidic devices based on mathematical simulations. Aggregated proteins (e.g., inclusion bodies) in solution with chaotropic agents (such as urea) at high concentration in combination with reducing agents are denatured. Refolding methods to achieve the native proteins from inclusion bodies of recombinant protein relying on denaturant dilution or dialysis approaches for suppressing protein aggregation is very important in the industrial field. In this paper, a modeling approach is... 

This paper presents a compact and cost effective method for on-chip separation of silica-coated magnetic nanoparticles (SMNPs) with different hydrodynamic size. Three types of SMNPs (Fe3O4@SiO2) with the same magnetic core but with different thickness of silica shells were successfully separated using the developed microfluidic platform. The innovative aspect of the presented separation method is that the induced velocity on the three different types of SMNPs while imposed to the same magnetic field gradient in a static fluid is inversely proportional to their overall, non-magnetic volume. This is due to the enhanced Stokes’ drag force exerted on the nanoparticles (NPs) resulting from their... 

Alzheimer’s disease (AD) is an irreversible neurological disorder that progresses gradually and can cause severe cognitive and behavioral impairments. This disease is currently considered a social and economic incurable issue due to its complicated and multifactorial characteristics. Despite decades of extensive research, we still lack definitive AD diagnostic and effective therapeutic tools. Consequently, one of the most challenging subjects in modern medicine is the need for the development of new strategies for the treatment of AD. A large body of evidence indicates that amyloid-β (Aβ) peptide fibrillation plays a key role in the onset and progression of AD. Recent studies have reported... 

In the current study, two series of antimicrobial dressings conjugated with silver sulfadiazine (SSD) and silver nanoparticles (AgNPs) were developed and evaluated for chronic wound healing. Highly porous polycaprolactone (PCL)/polyvinyl alcohol (PVA) nanofibers were loaded with different concentrations of SSD or AgNPs and compared comprehensively in vitro and in vivo. SSD and AgNPs indicated a strong and equal antimicrobial activity against S. aureus. However, SSD had more toxicity against fibroblast cells over one week in vitro culture. An in vivo model of wound healing on male Wistar rats was developed with a full thickness wound. All the wound dressings indicated enough flexibility and... 

Separation of circulating tumor cells (CTCs) from blood samples and subsequent DNA extraction from these cells play a crucial role in cancer research and drug discovery. Microfluidics is a versatile technology that has been applied to create niche solutions to biomedical applications, such as cell separation and mixing, droplet generation, bioprinting, and organs on a chip. Centrifugal microfluidic biochips created on compact disks show great potential in processing biological samples for point of care diagnostics. This study investigates the design and numerical simulation of an integrated microfluidic device, including a cell separation unit for isolating CTCs from a blood sample and a... 

Formation of the amyloid beta (Aβ) peptide aggregations represents an indispensable role in appearing and progression of Alzheimer disease. β-sheet breaker peptides can be designed and modified with different amino acids in order to improve biological properties and binding affinity to the amyloid beta peptide. In the present study, three peptide sequences were designed based on the hopeful results of LIAIMA peptide and molecular docking studies were carried out onto the monomer and fibril structure of amyloid beta peptide using AutoDock Vina software. According to the obtained interactions and binding energy from docking, the best-designed peptide (D-GABA-FPLIAIMA) was chosen and... 

Droplet generation is very important in biochemical processes such as cell encapsulation, digital PCR (Polymerase Chain Reaction), and drug delivery. In the present paper, a density-based method called “fluidic barrier” is introduced to produce multiple emulsions on a centrifugal microfluidic platform or Lab-on-a-CD (LOCD). We show that the density and the viscosity of the fluids involved are important parameters for predicting the characteristics of the droplets generated with this method. Moreover, we broadened this concept by using the fluidic barriers to separate reactive chemicals. As a proof of concept, alginate and CaCl2 solutions are separated by an oil barrier to control the... 

Cell-laden hydrogel microcapsules enable the high-throughput production of cell aggregates, which are relevant for three-dimensional tissue engineering and drug screening applications. However, current microcapsule production strategies are limited by their throughput, multistep protocols, and limited amount of compatible biomaterials. We here present a single-step process for the controlled microfluidic production of single-core microcapsules using enzymatic outside-in cross-linking of tyramine-conjugated polymers. It was hypothesized that a physically, instead of the conventionally explored biochemically, controlled enzymatic cross-linking process would improve the reproducibility,... 

We introduce a two-channel microfluidic atomic force microscopy (AFM) cantilever that combines the nanomechanical sensing functionality of an AFM cantilever with the ability to manipulate fluids of picolitres or smaller volumes through nanoscale apertures near the cantilever tip. Each channel is connected to a separate fluid reservoir, which can be independently controlled by pressure. Various systematic experiments with fluorescent liquids were done by either injecting the liquids from the on-chip reservoir or aspirating directly through the nanoscale apertures at the tip. A flow rate analysis of volume dosing, aspiration and concentration dosing inside the liquid medium was performed. To... 

Fabrication of well-ordered and bio-mimetic scaffolds is one of the most important research lines in tissue engineering. Different techniques have been utilized to achieve this goal, however, each method has its own disadvantages. Recently, melt electrowriting (MEW) as a technique for fabrication of well-organized scaffolds has attracted the researchers’ attention due to simultaneous use of principles of additive manufacturing and electrohydrodynamic phenomena. In previous research studies, polycaprolactone (PCL) has been mostly used in MEW process. PCL is a biocompatible polymer with characteristics that make it easy to fabricate well-arranged structures using MEW device. However, the... 

The integration of microfluidics with electrochemical analysis has resulted in the development of single miniaturized detection systems, which allows the precise control of sample volume with multianalyte detection capability in a cost- and time-effective manner. Microfluidic electrochemical sensing devices (MESDs) can potentially serve as precise sensing and monitoring systems for the detection of molecular markers in various detrimental diseases. MESDs offer several advantages, including (i) automated sample preparation and detection, (ii) low sample and reagent requirement, (iii) detection of multianalyte in a single run, (iv) multiplex analysis in a single integrated device, and (v)... 

Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 × 106 cells/mL... 

Organ-on-a-chip technology tries to mimic the complexity of native tissues in vitro. Important progress has recently been made in using this technology to study the gut with and without microbiota. These in vitro models can serve as an alternative to animal models for studying physiology, pathology, and pharmacology. While these models have greater physiological relevance than two-dimensional (2D) cell systems in vitro, endocrine and immunological functions in gut-on-a-chip models are still poorly represented. Furthermore, the construction of complex models, in which different cell types and structures interact, remains a challenge. Generally, gut-on-a-chip models have the potential to... 

Cell survival during the early stages of transplantation and before new blood vessels formation is a major challenge in translational applications of 3D bioprinted tissues. Supplementing oxygen (O2) to transplanted cells via an O2 generating source such as calcium peroxide (CPO) is an attractive approach to ensure cell viability. Calcium peroxide also produces calcium hydroxide that reduces the viscosity of bioinks, which is a limiting factor for bioprinting. Therefore, adapting this solution into 3D bioprinting is of significant importance. In this study, a gelatin methacryloyl (GelMA) bioink that is optimized in terms of pH and viscosity is developed. The improved rheological properties... 

Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high-efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label-free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor-intensive steps of labeling molecular signatures of cells. In general, microfluidic-based cell sorting approaches can separate cells using “intrinsic”...