A novel methodology for cancer diagnosis and treatment using new generation microfluidic devices: hydrodynamic cavitation on a chip

Hydrodynamic cavitation (HC) is a phase change phenomenon, where energy release in a fluid occurs upon the collapse of bubbles, which form due to the low local pressures. Although macro-scale hydrodynamic cavitation has a very destructive effect due to the high released energy from the cavitation bubble explosion, damaging effects of cavitation could be minimized and utilized for biomedical applications through micro-scale hydrodynamic cavitation inside a miniaturized microfluidic device. Since microfluidic devices enable the performance of controlled experiments by enabling spatial control over the cavitation process and by precisely monitoring its evolution. Early cancer diagnosis and effective therapeutic technologies appears to be inevitable needs for the human health. In this regard, this thesis presents comprehensive investigation and analysis related to role of the HC on circulating tumor cell (CTC) detection and cancer treatment through in vitro studies by utilizing cell culture and human blood samples. Performed in vitro experiments demonstrate that micro-scale HC, which is an emerging tool in biological applications, is a promising approach to investigate different cellular responses and to increase the chemotherapeutic efficacy of the anticancer drug and to rapidly detect CTCs

Hydrodynamic cavitation on a chip: a tool to detect circulating tumor cells

Circulating tumor cells (CTCs) are essential biomarkers for cancer diagnosis. Although various devices have been designed to detect, enumerate, and isolate CTCs from blood, some of these devices could have some drawbacks, such as the requirement of labeling, long process time, and high cost. Here, we present a microfluidic device based on the concept of "hydrodynamic cavitation-on-chip (HCOC)", which can detect CTCs in the order of minutes. The working principle relies on the difference of the required inlet pressure for cavitation inception of working fluids when they pass through the microfluidic device. The interface among the solid/floating particles, liquid, and vapor phases plays an important role in the strength of the fluid to withstand the rupture and cavitation formation. To this end, four experimental groups, including the "cell culture medium", "medium + Jurkat cells", "medium + Jurkat cells + CTCs", and "medium + CTCs", were tested as a proof of concept with two sets of fabricated microfluidic chips with the same geometrical dimensions, in which one set contained structural sidewall roughness elements. Jurkat cells were used to mimic white blood cells, and MDA-MB-231 cells were spiked into the medium as CTCs. Accordingly, the group with CTCs led to detectable earlier cavitation inception. Additionally, the effect of the CTC concentration on cavitation inception and the effect of the presence of sidewall roughness elements on the earlier inception were evaluated. Furthermore, CTC detection tests were performed with cancer cell lines spiked in blood samples from healthy donors. The results showed that this approach, HCOC, could be a potential approach to detect the presence of CTCs based on cavitation phenomenon and offer a cheap, user-friendly, and rapid tool with no requirement for any biomarker or extensive films acting as a biosensor. This approach also possesses straightforward application procedures to be employed for detection of CTCs

Fundamentals, biomedical applications and future potential of micro-scale cavitation-a review

Thanks to the developments in the area of microfluidics, the cavitation-on-a-chip concept enabled researchers to control and closely monitor the cavitation phenomenon in micro-scale. In contrast to conventional scale, where cavitation bubbles are hard to be steered and manipulated, lab-on-a-chip devices provide suitable platforms to conduct smart experiments and design reliable devices to carefully harness the collapse energy of cavitation bubbles in different bio-related and industrial applications. However, bubble behavior deviates to some extent when confined to micro-scale geometries in comparison to macro-scale. Therefore, fundamentals of micro-scale cavitation deserve in-depth investigations. In this review, first we discussed the physics and fundamentals of cavitation induced by tension-based as well as energy deposition-based methods within microfluidic devices and discussed the similarities and differences in micro and macro-scale cavitation. We then covered and discussed recent developments in bio-related applications of micro-scale cavitation chips. Lastly, current challenges and future research directions towards the implementation of micro-scale cavitation phenomenon to emerging applications are presented

Biomedical Applications of Microfluidic Devices: A Review

Both passive and active microfluidic chips are used in many biomedical and chemical applications to support fluid mixing, particle manipulations, and signal detection. Passive microfluidic devices are geometry-dependent, and their uses are rather limited. Active microfluidic devices include sensors or detectors that transduce chemical, biological, and physical changes into electrical or optical signals. Also, they are transduction devices that detect biological and chemical changes in biomedical applications, and they are highly versatile microfluidic tools for disease diagnosis and organ modeling. This review provides a comprehensive overview of the significant advances that have been made in the development of microfluidics devices. We will discuss the function of microfluidic devices as micromixers or as sorters of cells and substances (e.g., microfiltration, flow or displacement, and trapping). Microfluidic devices are fabricated using a range of techniques, including molding, etching, three-dimensional printing, and nanofabrication. Their broad utility lies in the detection of diagnostic biomarkers and organ-on-chip approaches that permit disease modeling in cancer, as well as uses in neurological, cardiovascular, hepatic, and pulmonary diseases. Biosensor applications allow for point-of-care testing, using assays based on enzymes, nanozymes, antibodies, or nucleic acids (DNA or RNA). An anticipated development in the field includes the optimization of techniques for the fabrication of microfluidic devices using biocompatible materials. These developments will increase biomedical versatility, reduce diagnostic costs, and accelerate diagnosis time of microfluidics technology

On the application of hydrodynamic cavitation on a chip in cellular injury and drug delivery

Hydrodynamic cavitation (HC) is a phase change phenomenon, where energy release in a fluid occurs upon the collapse of bubbles, which form due to the low local pressures. During recent years, due to advances in lab-on-a-chip technologies, HC-on-a-chip (HCOC) and its potential applications have attracted considerable interest. Microfluidic devices enable the performance of controlled experiments by enabling spatial control over the cavitation process and by precisely monitoring its evolution. In this study, we propose the adjunctive use of HC to induce distinct zones of cellular injury and enhance the anticancer efficacy of Doxorubicin (DOX). HC caused different regions (lysis, necrosis, permeabilization, and unaffected regions) upon exposure of different cancer and normal cells to HC. Moreover, HC was also applied to the confluent cell monolayer following the DOX treatment. Here, it was shown that the combination of DOX and HC exhibited a more pronounced anticancer activity on cancer cells than DOX alone. The effect of HC on cell permeabilization was also proven by using carbon dots (CDs). Finally, the cell stiffness parameter, which was associated with cell proliferation, migration and metastasis, was investigated with the use of cancer cells and normal cells under HC exposure. The HCOC offers the advantage of creating well-defined zones of bio-responses upon HC exposure simultaneously within minutes, achieving cell lysis and molecular delivery through permeabilization by providing spatial control. In conclusion, micro scale hydrodynamic cavitation proposes a promising alternative to be used to increase the therapeutic efficacy of anticancer drugs