Micromachines2016, 7(8), 130; doi:10.3390/mi7080130 - published 28 July 2016 Show/Hide Abstract
Abstract: With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment.
Micromachines2016, 7(8), 129; doi:10.3390/mi7080129 - published 26 July 2016 Show/Hide Abstract
Abstract: This paper proposes an optical fiber strain sensor based on packaged long-period fiber gratings (PLPFG) which is fabricated by the micro-electromechanical systems (MEMS) process and packaged with poly-dimethylsiloxane (PDMS) polymer materials. The optical fiber sensor packaged with PDMS improves robustness effectively. The proposed PLPFG sensors have periods of 610, 650, 660 μm and fiber diameter of 48, 60, 72 μm, respectively. The resonance dip of the PLPFG grows when a strain loaded onto the sensor. The results show that the largest strain sensitivity of the PLPFG strain sensor was −0.0652 dB/με from 0–1200 με and the linearity (R2) was 0.9812. Accordingly, the proposed PLPFG sensor has good potential for high-sensitivity strain sensing applications.
Micromachines2016, 7(7), 127; doi:10.3390/mi7070127 - published 21 July 2016 Show/Hide Abstract
Abstract: We describe a quantitative study of vortex generation due to non-equilibrium electrokinetics near a micro/nanochannel interface. The microfluidic device is comprised of a microchannel with a set of nanochannels. These perm-selective nanochannels induce flow instability and thereby produce strong vortex generation. We performed tracking visualization of fluorescent microparticles to obtain velocity fields. Particle tracking enables the calculation of an averaged velocity field and the velocity fluctuations. We characterized the effect of applied voltages and electrolyte concentrations on vortex formation. The experimental results show that an increasing voltage or decreasing concentration results in a larger vortex region and a strong velocity fluctuation. We calculate the normalized velocity fluctuation—whose meaning is comparable to turbulent intensity—and we found that it is as high as 0.12. This value is indicative of very efficient mixing, albeit with a small Reynolds number.
Micromachines2016, 7(7), 128; doi:10.3390/mi7070128 - published 21 July 2016 Show/Hide Abstract
Abstract: In this paper, we have systematically studied the holographic fabrication of three-dimensional (3D) structures using a single 3D printed reflective optical element (ROE), taking advantage of the ease of design and 3D printing of the ROE. The reflective surface was setup at non-Brewster angles to reflect both s- and p-polarized beams for the interference. The wide selection of reflective surface materials and interference angles allow control of the ratio of s- and p-polarizations, and intensity ratio of side-beam to central beam for interference lithography. Photonic bandgap simulations have also indicated that both s and p-polarized waves are sometimes needed in the reflected side beams for maximum photonic bandgap size and certain filling fractions of dielectric inside the photonic crystals. The flexibility of single ROE and single exposure based holographic fabrication of 3D structures was demonstrated with reflective surfaces of ROEs at non-Brewster angles, highlighting the capability of the ROE technique of producing umbrella configurations of side beams with arbitrary angles and polarizations and paving the way for the rapid throughput of various photonic crystal templates.
Micromachines2016, 7(7), 125; doi:10.3390/mi7070125 - published 20 July 2016 Show/Hide Abstract
Abstract: Field curvature and other aberrations are encountered inevitably when designing a compact fluorescence imaging system with a simple lens. Although multiple lens elements can be used to correct most such aberrations, doing so increases system cost and complexity. Herein, we propose a wide field-of-view (FOV) fluorescence imaging method with an unconventional optical-quality curved sample chamber that corrects the field curvature caused by a simple lens. Our optics simulations and proof-of-concept experiments demonstrate that a curved substrate with lens-dependent curvature can reduce greatly the distortion in an image taken with a conventional planar detector. Following the validation study, we designed a curved sample chamber that can contain a known amount of sample volume and fabricated it at reasonable cost using plastic injection molding. At a magnification factor of approximately 0.6, the curved chamber provides a clear view of approximately 119 mm2, which is approximately two times larger than the aberration-free area of a planar chamber. Remarkably, a fluorescence image of microbeads in the curved chamber exhibits almost uniform intensity over the entire field even with a simple lens imaging system, whereas the distorted boundary region has much lower brightness than the central area in the planar chamber. The absolute count of white blood cells stained with a fluorescence dye was in good agreement with that obtained by a commercially available conventional microscopy system. Hence, a wide FOV imaging system with the proposed curved sample chamber would enable us to acquire an undistorted image of a large sample volume without requiring a time-consuming scanning process in point-of-care diagnostic applications.
Micromachines2016, 7(7), 126; doi:10.3390/mi7070126 - published 20 July 2016 Show/Hide Abstract
Abstract: Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal models. In this regard, promising advances have recently been made by the so-called “organ-on-chip” (OOC) technology. By combining cell culture with microfluidics, biomedical researchers have started to develop microengineered models of the functional units of human organs. With the capacity to mimic physiological microenvironments and vascular perfusion, OOC devices allow the reproduction of tissue- and organ-level functions. When considering drug testing, nephrotoxicity is a major cause of attrition during pre-clinical, clinical, and post-approval stages. Renal toxicity accounts for 19% of total dropouts during phase III drug evaluation—more than half the drugs abandoned because of safety concerns. Mimicking the functional unit of the kidney, namely the nephron, is therefore a crucial objective. Here we provide an extensive review of the studies focused on the development of a nephron-on-chip device.