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Infrared thermographic images of the chip with temperature gradients: a ambient 230 ° C and hot bath temperature 600 ° C; b ambient 280 ° C and hot bath temperature 600 ° C; c ambient 190 ° C and hot bath temperature 700 ° C; d ambient 190 ° C and hot bath temperature 800 ° C.
Source publication
Studies on the effects of variations in temperature and mild temperature gradients on cells, gels, and scaffolds are important from the viewpoint of biological function. Small differences in temperature are known to elicit significant variations in cell behavior and individual protein reactivity. For the study of thermal effects and gradients in vi...
Citations
... Temperature gradient chamber fabrication. Temperature gradient chambers were manufactured based on a modification of the system described in Das et al. 49 , using ridged Plexiglas molds with ridge dimensions of 8.0 × 2.0 × 0.2 mm 3 (l:w:h) (Fig. 3a). As a heat source and heat sink, rectangular hollow copper reservoirs (18:6:8 mm 3 ) were used with inlets and outlets to supply heated and chilled water. ...
Cell migration plays an essential role in wound healing and inflammatory processes inside the human body. Peripheral blood neutrophils, a type of polymorphonuclear leukocyte (PMN), are the first cells to be activated during inflammation and subsequently migrate toward an injured tissue or infection site. This response is dependent on both biochemical signaling and the extracellular environment, one aspect of which includes increased temperature in the tissues surrounding the inflammation site. In our study, we analyzed temperature-dependent neutrophil migration using differentiated HL-60 cells. The migration speed of differentiated HL-60 cells was found to correlate positively with temperature from 30 to 42 °C, with higher temperatures inducing a concomitant increase in cell detachment. The migration persistence time of differentiated HL-60 cells was higher at lower temperatures (30–33 °C), while the migration persistence length stayed constant throughout the temperature range. Coupled with the increased speed observed at high temperatures, this suggests that neutrophils are primed to migrate more effectively at the elevated temperatures characteristic of inflammation. Temperature gradients exist on both cell and tissue scales. Taking this into consideration, we also investigated the ability of differentiated HL-60 cells to sense and react to the presence of temperature gradients, a process known as thermotaxis. Using a two-dimensional temperature gradient chamber with a range of 27–43 °C, we observed a migration bias parallel to the gradient, resulting in both positive and negative thermotaxis. To better mimic the extracellular matrix (ECM) environment in vivo, a three-dimensional collagen temperature gradient chamber was constructed, allowing observation of biased neutrophil-like differentiated HL-60 migration toward the heat source.
... According to the results, the device was able to operate with temperatures ranging between 2 °C and 37 °C using cooling and heating components (Figure 3a). A similar study was conducted by Das and coworkers [59], in which a microfluidic device to study the viability and activity of the cells under a temperature gradient was developed. Through numerical simulations, the temperature gradient that can be reached in the proposed chip was assessed, and it was found that the proposed chip is capable of creating temperature conditions that realistically mimic physiological/biological conditions (Figure 3b). ...
... Adapted from [58]; (b) temperature distribution in the chip in the incubator environment (370 K ambient and bath at 900 K). Adapted from [59]. ...
Numerical simulations have revolutionized research in several engineering areas by contributing to the understanding and improvement of several processes, being biomedical engineering one of them. Due to their potential, computational tools have gained visibility and have been increasingly used by several research groups as a supporting tool for the development of preclinical platforms as they allow studying, in a more detailed and faster way, phenomena that are difficult to study experimentally due to the complexity of biological processes present in these models—namely, heat transfer, shear stresses, diffusion processes, velocity fields, etc. There are several contributions already in the literature, and significant advances have been made in this field of research. This review provides the most recent progress in numerical studies on advanced microfluidic devices, such as organ-on-a-chip (OoC) devices, and how these studies can be helpful in enhancing our insight into the physical processes involved and in developing more effective OoC platforms. In general, it has been noticed that in some cases, the numerical studies performed have limitations that need to be improved, and in the majority of the studies, it is extremely difficult to replicate the data due to the lack of detail around the simulations carried out.
... The miniaturization in microfluidics helps reduce the thermal mass, thereby leading to increases in precision and sensitivity, reduction of power consumption, and shorter time scales for heating and cooling. Micro Polymerase Chain Reaction (µPCR) for rapid DNA amplification through thermal cycling, Temperature Gradient Focusing (TGF), and studies of protein behavior under thermal gradients [8,9] are few notable examples for the application of microscale thermal reactors [1]. ...
... For instance, TGF as a technique for focusing and separating the species in the microchannel requires a comparatively wide thermal gradient [25]. Das et al. applied a moderate thermal gradient (0.4-1.4 K/mm) generated by counter-current heat exchanger over a well-based PDMS reactor to analyze the activity of the cells under the thermal gradient [9]. ...
This work presents a novel counter-flow design for stabilizing microfluidic thermal reactors. In such devices, the substrate material is held in an unchanging thermal state while any combination of isothermal and gradient regions may be enacted on the surface region, all of which are stable in time. When such a state is achieved, precise control of the temporal temperature of the moving liquid is possible. The aim of this work is to establish a linear thermal gradient within the microfluidic reactor under a no-flow condition and to maintain the temperature profile for a broad range of flow conditions. Experimental results show that counter-flow will have a powerful stabilizing effect: isothermal regions remain isothermal, and gradient regions linearize. Distortions due to both external and internal convection/advection are reduced by several orders of magnitude. Counter-flow and direct-flow glass composite devices with different interlayer materials (silicon, quartz, and glass) were fabricated to investigate the role of interlayer thermal conductivity. The best performance was achieved for a counter-flow case with silicon interlayer for which a wide and stable linear thermal gradient (1 K/mm) was established, enabling ramp rates of up to 143 K/s. 3-D numerical models are used to predict the in-channel fluid temperature and its relation with device surface temperature, as well as evaluate the performance of the devices under other heating configurations.
... Thermal gradient-based pumps employ a temperature difference to induce fluid transport in microfluidics (Salari et al. 2019). Flow rate control in such pumps is achieved through adjusting the temperature gradient within the fluid which may not be suitable for biomedical applications due to potential thermal damage to biomaterials (Das et al. 2008). Although peristaltic microfluidic pumps, which have been widely explored for on-chip fluid handling, provide relatively cheaper alternatives that are generally capable of higher flow rates, they have various drawbacks including potential detrimental effects to cells due to pulsatile flows (Li et al. 2013), poor long-time durability due to constant deformations, and limited flow profiles (Stewart 2019). ...
Simple and low-cost solutions are becoming extremely important for the evolving necessities of biomedical applications. Even though, on-chip sample processing and analysis has been rapidly developing for a wide range of screening and diagnostic protocols, efficient and reliable fluid manipulation in microfluidic platforms still require further developments to be considered portable and accessible for low-resource settings. In this work, we present an extremely simple microfluidic pumping device based on three-dimensional (3D) printing and acoustofluidics. The fabrication of the device only requires 3D-printed adaptors, rectangular glass capillaries, epoxy and a piezoelectric transducer. The pumping mechanism relies on the flexibility and complexity of the acoustic streaming patterns generated inside the capillary. Characterization of the device yields controllable and continuous flow rates suitable for on-chip sample processing and analysis. Overall, a maximum flow rate of ~ 12 μL/min and the control of pumping direction by frequency tuning is achieved. With its versatility and simplicity, this microfluidic pumping device offers a promising solution for portable, affordable and reliable fluid manipulation for on-chip applications.
Supplementary information:
The online version contains supplementary material available at 10.1007/s10404-020-02411-w.
... For analyzing thermal problems in biology, numerical model not only serves as a quick, accurate and low-cost method but also enables researchers to simultaneously optimize other parameters such as device dimensions. Das et al. reported a microfluidic device for studying the function of cells under a temperature gradient [71]. ...
Microfluidics has been demonstrating enormous potential through its role in recent advances in biological sciences. However, designing a new and customized microfluidic platform, gaining a better understanding of its function and the underlying physics still pose significant technical challenges. On the one hand, experimental approaches have been commonly used for the development of microfluidic devices since they are accurate and evidence-based methods. However, these approaches are expensive and laborious. Numerical approaches, on the other hand, are now recognized as a reliable complementary method to reducing cost, time, and effort and being relatively accurate. This paper systematically reviews the capability of numerical approaches in developing efficient microfluidic technologies for cell analysis. Moreover, this paper provides an initial insight for researchers who are interested in establishing numerical approaches for microfluidic cell analysis platforms.
... INTRODUCTION When working on biologic systems like cell cultures, environmental conditions need to be accurately controlled to obtain physiologically relevant data during the cell study [1,2]. Commonly, bulky incubators are used to regulate both temperature and surrounding gas composition. ...
In this paper, we present a platform composed of three transparent heater-sensor microsystems capable of maintaining a cell culture at a desired temperature. Accurate and stable temperature conditions are therefore accessible throughout the entire culture cycle.
... Additionally, the Joule heating driven by the applied electric field increases the temperature in the OEK chip further, similar to the conditions of dielectrophoresis (DEP)-based manipulations 27,30 . For biological applications, small temperature differences may induce significant variations in cell behavior and activity and protein reactivity [30][31][32] . Irreversible cell damage or death can arise from either a short, sharp increase or a sustained moderate increase in temperature 33,34 . ...
... This temperature gradient will induce thermophoresis in the cell, influencing molecular movement across the cytoplasm 37 . The temperature gradient along the PS chip will also influence the viability and activity of cells located in different positions 31 . Therefore, for biological applications, the light pattern must be properly designed to generate heat satisfying the cell requirements, and the temperature gradient must be decreased to minimize negative effects, e.g., thermophoresis. ...
Optically induced electrokinetics (OEK)-based technologies, which integrate the high-resolution dynamic addressability of optical tweezers and the high-throughput capability of electrokinetic forces, have been widely used to manipulate, assemble, and separate biological and non-biological entities in parallel on scales ranging from micrometers to nanometers. However, simultaneously introducing optical and electrical energy into an OEK chip may induce a problematic temperature increase, which poses the potential risk of exceeding physiological conditions and thus inducing variations in cell behavior or activity or even irreversible cell damage during bio-manipulation. Here, we systematically measure the temperature distribution and changes in an OEK chip arising from the projected images and applied alternating current (AC) voltage using an infrared camera. We have found that the average temperature of a projected area is influenced by the light color, total illumination area, ratio of lighted regions to the total controlled areas, and amplitude of the AC voltage. As an example, optically induced thermocapillary flow is triggered by the light image-induced temperature gradient on a photosensitive substrate to realize fluidic hydrogel patterning. Our studies show that the projected light pattern needs to be properly designed to satisfy specific application requirements, especially for applications related to cell manipulation and assembly.
... Second, in the Minihypoxy system, the cells are steadily kept on a heat plate, which eliminates the stress effects caused by the temperature changes. Even small temperature changes might affect significantly the behaviour of cells [42,43]. Third, the pH changes in the Minihypoxy system are minimized compared to other hypoxia systems as the constant CO 2 supply maintains the buffering capacity of the media. ...
Background:
Cells in solid tumours are variably hypoxic and hence resistant to radiotherapy - the essential role of oxygen in the efficiency of irradiation has been acknowledged for decades. However, the currently available methods for performing hypoxic experiments in vitro have several limitations, such as a limited amount of parallel experiments, incapability of keeping stable growth conditions and dependence on CO2 incubator or a hypoxia workstation. The purpose of this study was to evaluate the usability of a novel portable system (Minihypoxy) in performing in vitro irradiation studies under hypoxia, and present supporting biological data.
Materials and methods:
This study was conducted on cancer cell cultures in vitro. The cells were cultured in normoxic (~ 21% O2) or in hypoxic (1% O2) conditions either in conventional hypoxia workstation or in the Minihypoxy system and irradiated at dose rate 1.28 Gy/min ± 2.9%. The control samples were sham irradiated. To study the effects of hypoxia and irradiation on cell viability and DNA damage, western blotting, immunostainings and clonogenic assay were used. The oxygen level, pH, evaporation rate and osmolarity of the culturing media on cell cultures in different conditions were followed.
Results:
The oxygen concentration in interest (5, 1 or 0% O2) was maintained inside the individual culturing chambers of the Minihypoxy system also during the irradiation. The radiosensitivity of the cells cultured in Minihypoxy chambers was declined measured as lower phosphorylation rate of H2A.X and increased clonogenic capacity compared to controls (OER~ 3).
Conclusions:
The Minihypoxy system allows continuous control of hypoxic environment in multiple wells and is transportable. Furthermore, the system maintains the low oxygen environment inside the individual culturing chambers during the transportation and irradiation in experiments which are typically conducted in separate facilities.
... Nano-architectural effects on implant interface have been investigated for silicon, titanium, and some polymethyl methacrylate (PMMA)-based electrodes. Many methods can be used to create the nano-architecture on substrates, such as photolithography, optical lithography, soft lithography, nano-sphere lithography, and nano-stencil (Blattler et al., 2006;Kriparamanan et al., 2006;Das et al., 2008;Ding et al., 2010). The benefits of using fabrication methods discussed below, is to create specific patterns, geometries, and sizes that are reproducible. ...
Intracortical microelectrodes (IME) are neural devices that initially were designed to function as neuroscience tools to enable researchers to understand the nervous system. Over the years, technology that aids interfacing with the nervous system has allowed the ability to treat patients with a wide range of neurological injuries and diseases. Despite the substantial success that has been demonstrated using IME in neural interface applications, these implants eventually fail due to loss of quality recording signals. Recent strategies to improve interfacing with the nervous system have been inspired by methods that mimic the native tissue. This review focusses on one strategy in particular, nano-architecture, a term we introduce that encompasses the approach of roughening the surface of the implant. Various nano-architecture approaches have been hypothesized to improve the biocompatibility of IMEs, enhance the recording quality, and increase the longevity of the implant. This review will begin by introducing IME technology and discuss the challenges facing the clinical deployment of IME technology. The biological inspiration of nano-architecture approaches will be explained as well as leading fabrication methods used to create nano-architecture and their limitations. A review of the effects of nano-architecture surfaces on neural cells will be examined, depicting the various cellular responses to these modified surfaces in both in vitro and pre-clinical models. The proposed mechanism elucidating the ability of nano-architectures to influence cellular phenotype will be considered. Finally, the frontiers of next generation nano-architecture IMEs will be identified, with perspective given on the future impact of this interfacing approach.
... However, no microfluidic device for thermotaxis of blood cells such as leukocytes has been developed yet, although their thermotactic response was reported years ago [78]. Thermotaxis in microfluidics can be conducted using microfluidic thermal gradient systems (µTGS) in which a thermal gradient is generated by a counterflow heat exchanger, as shown in Figure 3 [79]. The main advantage of these systems is eliminating joule heating and the need for metal elements. ...
Taxis has been reported in many cells and microorganisms, due to their tendency to migrate toward favorable physical situations and avoid damage and death. Thermotaxis and chemotaxis are two of the major types of taxis that naturally occur on a daily basis. Understanding the details of the thermo- and chemotactic behavioral response of cells and microorganisms is necessary to reveal the body function, diagnosing diseases and developing therapeutic treatments. Considering the length-scale and range of effectiveness of these phenomena, advances in microfluidics have facilitated taxis experiments and enhanced the precision of controlling and capturing microscale samples. Microfabrication of fluidic chips could bridge the gap between in vitro and in situ biological assays, specifically in taxis experiments. Numerous efforts have been made to develop, fabricate and implement novel microchips to conduct taxis experiments and increase the accuracy of the results. The concepts originated from thermo- and chemotaxis, inspired novel ideas applicable to microfluidics as well, more specifically, thermocapillarity and chemocapillarity (or solutocapillarity) for the manipulation of single- and multi-phase fluid flows in microscale and fluidic control elements such as valves, pumps, mixers, traps, etc. This paper starts with a brief biological overview of the concept of thermo- and chemotaxis followed by the most recent developments in microchips used for thermo- and chemotaxis experiments. The last section of this review focuses on the microfluidic devices inspired by the concept of thermo- and chemotaxis. Various microfluidic devices that have either been used for, or inspired by thermo- and chemotaxis are reviewed categorically.
