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Tunable and reproducible size with high circularity is an important limitation to obtain three-dimensional (3D) cellular structures and spheroids in scaffold free tissue engineering approaches. Here, we present a facile methodology based on magnetic levitation (MagLev) to fabricate 3D cellular structures rapidly and easily in high-volume and low magnetic field. In this study, 3D cellular structures were fabricated using magnetic levitation directed assembly where cells are suspended and self-assembled by contactless magnetic manipulation in the presence of a paramagnetic agent. The effect of cell seeding density, culture time, and paramagnetic agent concentration on the formation of 3D cellular structures was evaluated for NIH/3T3 mouse fibroblast cells. In addition, magnetic levitation guided cellular assembly and 3D tumor spheroid formation was examined for five different cancer cell lines: MCF7 (human epithelial breast adenocarcinoma), MDA-MB-231 (human epithelial breast adenocarcinoma), SH-SY5Y (human bone-marrow neuroblastoma), PC-12 (rat adrenal gland pheochromocytoma), and HeLa (human epithelial cervix adenocarcinoma). Moreover, formation of a 3D coculture model was successfully observed by using MDA-MB-231 dsRED and MDA-MB-231 GFP cells. Taken together, these results indicate that the developed MagLev setup provides an easy and efficient way to fabricate 3D cellular structures and may be a feasible alternative to conventional methodologies for cellular/multicellular studies.

This work describes development of smartphone-assisted magnetic levitation assay for Point-of-Care (PoC) applications. Magnetic levitation is a technique that detects and separates particles based on their density differences in a magnetic field. Observation of the levitated micro-particles is mainly performed by light microscope or additional optical components, which mostly limits applicability of the magnetic levitation technique for PoC diagnostics. In this paper, we demonstrated the capability of the smartphone assisted-magnetic levitation platform for Hepatitis C (HCV) detection assay. This method utilizes microsensor beads (MS beads) that are functionalized with anti-HCV NS3 antibody. First, the magnetic levitation platform was optimized via density marker polyethylene beads (DMB); then HCV NS3 protein was successfully detected based on levitation height differences of MS beads caused by density changes. The capability of the magnetic levitation platform for HCV detection was determined as almost 10-fold sensitive compared to conventional techniques such as enzyme-linked immunosorbent assay (ELISA). The imaging capability and resolution of the setup was improved over previously used configurations, and the developed platform enabled visualization of micro-scale objects only by smartphone assistance. This method requires no power, it is an easy-to-use and cost effective, therefore it could be easily adaptable to varied sensing assays as PoC tool.

Microfluidic systems are relatively new technology field with a constant need of novel and practical manufacturing materials and methods. One of the main shortcomings of current methods is the inability to provide rapid bonding, with high bonding strength, and sound microchannel integrity. Herein we propose a novel method of assembly that overcomes the mentioned limitations. Polymer-assisted bonding is a novel, rapid, simple, and inexpensive method where a polymer is solubilized in a solvent and the constituted solution is used as a bonding agent. In this study, we combined this method with utilization of several phase-changing materials (PCMs) as channel-protective agents. Glauber’s salt appeared to be more suitable as a channel-protective agent compared to rest of the salts that have been used in this study. Based on the bonding strength, quality analyses, leakage tests, and SEM imaging, the superior assisting bonding solvent was determined to be dichloromethane with a PMMA concentration of 2.5% (W/V). It showed a bonding strength of 23.794 MPa and a nearly non-visible bonding layer formation of 2.83 µm in width which is proved by SEM imaging. The said combination of PCM, solvent, and polymer concentration also showed success in leakage tests and an application of micro-droplet generator fabrication. The application was carried out to test the applicability of developed prototyping methodology, which resulted in conclusive outcomes as the droplet generator simulation run in COMSOL Multiphysics version 5.1 software. In conclusion, the developed fabrication method promises simple, rapid, and strong bonding with sharp and clear micro-channel engraving.

Electrospun collagen is commonly used as a scaffold in tissue engineering applications since it mimics the content and morphology of native extracellular matrix (ECM) well. This report describes “toxic solvent free” fabrication of electrospun hybrid scaffold consisting of Collagen (Col) and Poly( l -lactide-co-e-caprolactone) (PLLCL) for three-dimensional (3D) cell culture. Biomimetic hybrid scaffold was fabricated via co-spinning approach where simultaneous electrospinning of PLLCL and Collagen was mediated by polymer sacrificing agent Polyvinylpyrrolidone (PVP). Acidified aqueous solution of PVP was used to solubilize collagen without using toxic solvents for electrospinning, and then PVP was readily removed by rinsing in water. Mechanical characterizations, protein adsorption, as well as biodegradation analysis have been conducted to investigate feasibility of biomimetic hybrid scaffold for 3D cell culture applications. Electrospun biomimetic hybrid scaffold, which has 3D-network structure with 300–450 nm fiber diameters, was found to be maximizing cell adhesion through assisting NIH 3T3 mouse fibroblast cells. 3D cell culture studies confirmed that presence of collagen in biomimetic hybrid scaffold have created a major impact on cell proliferation compared to conventional 2D systems on long-term, also cell viability increased with the increasing amount of collagen.

Nanotechnological approaches are the latest modality for early stage detection of cancer. The need of rapid, non-invasive, patient specific, and informative techniques in cancer diagnostics lead to the utilization of nanotechnology, microfluidics, and lab-on-a-chip platforms for liquid biopsy, and the developments through these technologies increased the knowledge also for case specific applications. In this review, nanotechnology-based methodologies that are developed in the last decade for cancer diagnostics are investigated and are discussed under four main categories for the purpose of simplification as; nanochip based, nanofilm based, magnetic nanomaterial-based methods, and combinational utilization of multiple methodologies. We suggest a combinational approach on device development with an aim of producing a compact, cost effective, rapid, sensitive, and non-invasive diagnostic device as a conclusion of literature review.

Contactless manipulation of small objects, such as micro−/nanoparticles, biological entities, and even cells is required in varied applications in biosciences. Magnetic levitation (MagLev) is a new-generation methodology to achieve contactless magnetic manipulation of objects. Lately, magnetic levitation methodology has been utilized in several applications in bioscience, such as biosensors, diagnostics and tissue engineering. Magnetic levitation enables separation or positioning of objects in three-dimensional (3D) space based on their density features. Therefore, density-based separation assays utilizing magnetic levitation for biosensing or diagnostic purposes are developed recently. Specific particles or cells, which are markers of any disease, could be detected by sorting them based on density differences through magnetic levitation. On the other hand, tissue engineering studies and production of self-assembled 3D cell culture structures are carried out by magnetic levitation, where cells are magnetically positioned while allowing cell-cell interaction resulting in 3D cell culture formation. Lately, magnetic levitation methodologies received more interest in the field of bioscience due to advantages about the efficiency and cost. This contribution broadly summarizes recent efforts in magnetic levitation techniques that are mainly applied in diagnostics and tissue engineering.

Natural gums and mucilages from plant-derived polysaccharides are potential candidates for a tissue-engineering scaffold by their ability of gelation and biocompatibility. Herein, we utilized Glucuronoxylan-based quince seed hydrogel (QSH) as a scaffold for tissue engineering applications. Optimization of QSH gelation was conducted by varying QSH and crosslinker glutaraldehyde (GTA) concentrations. Structural characterization of QSH was done by Fourier Transform Infrared Spectroscopy (FTIR). Furthermore, morphological and mechanical investigation of QSH was performed by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The protein adsorption test revealed the suitability of QSH for cell attachment. Biocompatibility of QSH was confirmed by culturing NIH-3T3 mouse fibroblast cells on it. Cell viability and proliferation results revealed that optimum parameters for cell viability were 2 mg mL−1 of QSH and 0.03 M GTA. SEM and DAPI staining results indicated the formation of spheroids with a diameter of approximately 300 μm. Furthermore, formation of extracellular matrix (ECM) microenvironment was confirmed with the Collagen Type-I staining. Here, it was demonstrated that the fabricated QSH is a promising scaffold for 3D cell culture and tissue engineering applications provided by its highly porous structure, remarkable swelling capacity and high biocompatibility.

This review discusses biocompatible hydrogels and stimuli-responsive 3D networking polymeric materials and building blocks of nanopharmaceuticals. We aimed to outline the basics of gels and hydrogels, responsive behaviors, and applications such as therapeutic and drug carriers, bioimaging agents, biosensing elements. The review also covers significant challenges, limitations, opportunities, new approaches, and future perspective. We review the general aspects of hydrogels to refresh the basic knowledge and theory that is covered in the section “General Properties of the Gels.” It discusses green synthesis of nanogels, swelling, and responsive and mechanical behavior of the gels. We also reviewed the broad applications of gels including therapeutic agent carriers, drug, protein, and genetic material delivery systems. In a separate section, biosensing and imaging applications have been reviewed from recent reports. Overall we highlighted advantages of hydrogels and their evolution that providing broad functionality, stability, and responsiveness as well as low toxicity. We also discussed the limitations and challenges as well as unique opportunities for developing alternative synthesis and processing strategies that revolutionize common understandings. In the last section, as closing remarks, the future needs in nanopharmaceutical applications have been elaborately articulated, and the combination of biomimetic-synthetic hydrogels and biocompatibility has been discussed.

Conventional drug discovery and screening processes have important drawbacks particularly in preclinical phase which include in vitro drug screening test, namely, 2D cell culture, and in vivo test on animal models. It is known that 2D cell cultures are insufficient to indicate drug response of real tissues and organs. Animal models also mislead about drug response with the same reason, and there are some ethical issues about animal models as well. These drawbacks lead to failure of drug candidate at later phases or after approved by the Food and Drug Administration (FDA). Since the drug development phases are very costly processes, this failure means time and money consumption to drug companies. More importantly if the drug fails after approval, many patients will be exposed and be affected by its side effects.

Arslan Yildiz, Ahu/0000-0003-0348-0575, WOS: 000427539200003, The magnetic levitation technique has been utilized to orientate and manipulate objects both in two dimensions (2D) and three dimensions (3D) to form complex structures by combining various types of materials. Magnetic manipulation holds great promise for several applications such as self-assembly of soft substances and biological building blocks, manipulated tissue engineering, as well as cell or biological molecule sorting for diagnostic purposes. Recent studies are proving the potential of magnetic levitation as an emerging tool in biotechnology. This review outlines the advances of newly developing magnetic levitation technology on biological applications in aqueous environment from the biotechnology perspective.

Arslan Yildiz, Ahu/0000-0003-0348-0575; Turker, Esra/0000-0002-9328-5513, WOS: 000447710700007, PubMed: 29700506, Three-dimensional (3D) cell culture has emerged as a pioneering methodology and is increasingly utilized for tissue engineering, 3D bioprinting, cancer model studies and drug development studies. The 3D cell culture methodology provides artificial and functional cellular constructs serving as a modular playground prior to animal model studies, which saves substantial efforts, time and experimental costs. The major drawback of current 3D cell culture methods is their dependency on biocompatible scaffolds, which often require tedious syntheses and fabrication steps. Herein, we report an easy-to-use methodology for the formation of scaffold-free 3D cell culture and cellular assembly via magnetic levitation in the presence of paramagnetic agents. To paramagnetize the cell culture environment, three different Gadolinium(III) chelates were utilized, which led to levitation and assembly of cells at a certain levitation height. The assembly and close interaction of cells at the levitation height where the magnetic force was equilibrated with gravitational force triggered the formation of complex 3D cellular structures. It was shown that Gd(III) chelates provided an optimal levitation that induced intercellular interactions in scaffold-free format without compromising cell viability. NIH 3T3 mouse fibroblasts and HCC827 non-small-cell lung cancer cells were evaluated via the magnetic levitation system, and the formation of 3D cell culture models was validated for both cell lines. Hereby, the developed magnetic levitation system holds promises for complex cellular assemblies and 3D cell culture studies.