A micropillar array-based microfluidic chip for label-free separation of circulating tumor cells: The best micropillar geometry?

Introduction The information derived from the number and characteristics of circulating tumor cells (CTCs), is crucial to ensure appropriate cancer treatment monitoring. Currently, diverse microfluidic platforms have been developed for isolating CTCs from blood, but it remains a challenge to develop a low-cost, practical, and efficient strategy. Objectives This study aimed to isolate CTCs from the blood of cancer patients via introducing a new and efficient micropillar array-based microfluidic chip (MPA-Chip), as well as providing prognostic information and monitoring the treatment efficacy in cancer patients. Methods We fabricated a microfluidic chip (MPA-Chip) containing arrays of micropillars with different geometries (lozenge, rectangle, circle, and triangle). We conducted numerical simulations to compare velocity and pressure profiles inside the micropillar arrays. Also, we experimentally evaluated the capture efficiency and purity of the geometries using breast and prostate cancer cell lines as well as a blood sample. Moreover, the device’s performance was validated on 12 patients with breast cancer (BC) in different states. Results The lozenge geometry was selected as the most effective and optimized micropillar design for CTCs isolation, providing high capture efficiency (>85 %), purity (>90 %), and viability (97 %). Furthermore, the lozenge MPA-chip was successfully validated by the detection of CTCs from 12 breast cancer (BC) patients, with non-metastatic (median number of 6 CTCs) and metastatic (median number of 25 CTCs) diseases, showing different prognoses. Also, increasing the chemotherapy period resulted in a decrease in the number of captured CTCs from 23 to 7 for the metastatic patient. The MPA-Chip size was only 0.25 cm2 and the throughput of a single chip was 0.5 ml/h, which can be increased by multiple MPA-Chips in parallel. Conclusion The lozenge MPA-Chip presented a novel micropillar geometry for on-chip CTC isolation, detection, and staining, and in the future, the possibilities can be extended to the culture of the CTCs

Recapitulating the Vasculature using organ-on-chip technology

\u3cp\u3eThe development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.\u3c/p\u3

Reynolds number effects in a turbulent pipe flow for low to moderate Re

We present in this paper high resolution, two-dimensional LDV measurements in a turbulent pipe flow of water over the Reynolds number range 500025000. Results for the turbulence statistics up to the fourth moment are presented, as well as power spectra in the near-wall region. These results clearly show that the turbulence statistics scaled on inner variables are Reynolds-number dependent in the aforementioned range of Reynolds numbers. For example, the constants in the dimensionless logarithmic mean-velocity profile are shown to vary with Reynolds number. Our conclusion that turbulence statistics depend on the Reynolds number is consistent with results found in other flow configurations, e.g., a channel flow. Our results for the pipe flow, however, lead nevertheless to quite different tendencies

Magnetically actuated artificial cilia: the effect of fluid inertia.

Natural cilia are hairlike microtubule-based structures that are able to move fluid on the micrometer scale using asymmetric motion. In this article, we follow a biomimetic approach to design artificial cilia lining the inner surfaces of microfluidic channels with the goal of propelling fluid. The artificial cilia consist of polymer films filled with superparamagnetic nanoparticles, which can mimic the motion of natural cilia when subjected to a rotating magnetic field. To obtain the magnetic field and associated magnetization local to the cilia, we solve the Maxwell equations, from which the magnetic body moments and forces can be deduced. To obtain the ciliary motion, we solve the dynamic equations of motion, which are then fully coupled to the Navier-Stokes equations that describe the fluid flow around the cilia, thus taking full account of fluid inertial forces. The dimensionless parameters that govern the deformation behavior of the cilia and the associated fluid flow are arrived at using the principle of virtual work. The physical response of the cilia and the fluid flow for different combinations of elastic, fluid viscous, and inertia forces are identified

Workshop meeting report Organs-on-Chips : human disease models

The concept of Organs-on-Chips has recently evolved and has been described as 3D (mini-) organs or tissues consisting of multiple and different cell types interacting with each other under closely controlled conditions, grown in a microfluidic chip, and mimicking the complex structures and cellular interactions in and between different cell types and organs in vivo, enabling the real time monitoring of cellular processes. In combination with the emerging iPSC (induced pluripotent stem cell) field this development offers unprecedented opportunities to develop human in vitro models for healthy and diseased organ tissues, enabling the investigation of fundamental mechanisms in disease development, drug toxicity screening, drug target discovery and drug development, and the replacement of animal testing. Capturing the genetic background of the iPSC donor in the organ or disease model carries the promise to move towards in vitro clinical trials , reducing costs for drug development and furthering the concept of personalized medicine and companion diagnostics. During the Lorentz workshop (Leiden, September 2012) an international multidisciplinary group of experts discussed the current state of the art, available and emerging technologies, applications and how to proceed in the field. Organ-on-a-chip platform technologies are expected to revolutionize cell biology in general and drug development in particular

Micro-moulded magnetic artificial cilia for anti-fouling surfaces

Cilia are microscopic hair-like filaments found in nature which can perform such functionalities as swimming, feeding, and particle manipulation [1]. The particle manipulation property of cilia has been extensively studied by the group of prof. Anna Balazs and co-workers using computational modelling [2]. Inspired by these, we propose the use of artificial cilia to create anti-fouling surfaces in man-made applications.\u3cbr/\u3eWe have fabricated magnetically actuated artificial cilia using an out-of-cleanroom, cost-effective and time-saving method – micro-moulding technology. The moulding process consists of seven steps: (1) moulds featured micro-holes are fabricated using photo-lithography; (2) a mixture composed of a base PDMS + curing agent and iron particles (P-I) is poured onto the mould, followed by a degassing procedure; (3) the top part of P-I which is outside of the micro-holes, is removed; (4) the mould is placed in a uniform magnetic field to align the iron particles; (5) pure base PDMS + curing agent are poured onto the mould, which will form the so-called base for cilia; (6) the liquid-like composition which covers the mould is cured in an oven; (7) the cured P-I – PDMS is peeled off the mould. Finally, we obtain magnetic artificial cilia, which “stand” on a transparent PDMS base (Fig. 2).\u3cbr/\u3eMagnetic artificial cilia made with the micro-moulding method can perform a tilted conical movement mimicking the motion of cilia in nature, which is achieved by positioning a rotating magnet underneath the PDMS base. An actuation video can be found on https://www.youtube.com/watch?v=9KVCVMa3Lvk . Our next step is to characterize the particle manipulation capability of our cilia and then to create an anti-fouling surface