Organ-on-a-chip (OoC) devices require the precise control of various media. This is mostly done using several fluid control components, which are much larger than the typical OoC device and connected through fluidic tubing, i.e., the fluidic system is not integrated, which inhibits the system’s portability. Here, we explore the limits of fluidic system integration using off-the-shelf fluidic control components. A flow control configuration is proposed that uses a vacuum to generate a fluctuation-free flow and minimizes the number of components used in the system. 3D printing is used to fabricate a custom-designed platform box for mounting the chosen smallest footprint components. It provides flexibility in arranging the various components to create experiment-specific systems. A demonstrator system is realized for lung-on-a-chip experiments. The 3D-printed platform box is 290 mm long, 240 mm wide and 37 mm tall. After integrating all the components, it weighs 4.8 kg. The system comprises of a switch valve, flow and pressure controllers, and a vacuum pump to control the diverse media flows. The system generates liquid flow rates ranging from 1.5 μ Lmin ^{- 1} to 68 μ Lmin ^{- 1} in the cell chambers, and a cyclic vacuum of 280 mbar below atmospheric pressure with 0.5 Hz frequency in the side channels to induce mechanical strain on the cells-substrate. The components are modular for easy exchange. The battery operated platform box can be mounted on either upright or inverted microscopes and fits in a standard incubator. Overall, it is shown that a compact integrated and portable fluidic system for OoC experiments can be constructed using off-the-shelf components. For further down-scaling, the fluidic control components, like the pump, switch valves, and flow controllers, require significant miniaturization while having a wide flow rate range with high resolution.

Reciprocating piezoelectric micropumps enable miniaturization in microfluidics for lab-on-a-chip applications such as organs-on-chips (OoC). However, achieving a steady flow when using these micropumps is a significant challenge because of flow ripples in the displaced liquid, especially at low frequencies or low flow rates (<50 µL/min). Although dampers are widely used for reducing ripples in a flow, their efficiency depends on the driving frequency of the pump. Here, we investigated multi-phase rectification as an approach to minimize ripples at low flow rates by connecting piezoelectric micropumps in parallel. The efficiency in ripple reduction was evaluated with an increasing number (n) of pumps connected in parallel, each actuated by an alternating voltage waveform with a phase difference of 2π/n (called multi-phase rectification) at a chosen frequency. We introduce a fluidic ripple factor ((Formula presented.)), which is the ratio of the root mean square ((Formula presented.)) value of the fluctuations present in the rectified output to the average fluctuation-free value of the discharge flow, as a metric to express the quality of the flow. The fluidic ripple factor was reduced by more than 90% by using three-phase rectification when compared to one-phase rectification in the 2–60 μL/min flow rate range. Analytical equations to estimate the fluidic ripple factor for a chosen number of pumps connected in parallel are presented, and we experimentally confirmed up to four pumps. The analysis shown can be used to design a frequency-independent multi-phase fluid rectifier to the desired ripple level in a flow for reciprocating pumps.

Microfluidic organs-on-chips (OoCs) technology has emerged as the trend for in vitro functional modeling of organs in recent years. Simplifying the complexities of the human organs under controlled perfusion of required fluids paves the way for accurate prediction of human organ functionalities and their response to interventions like exposure to drugs. However, in the state-of-the-art OoC, the existing methods to control fluids use external bulky peripheral components and systems much larger than the chips used in experiments. A new generation of compact microfluidic flow control systems is needed to overcome this challenge. This study first presents a structured classification of OoC devices according to their types and microfluidic complexities. Next, we suggest three fundamental fluid flow control mechanisms and define component configurations for different levels of OoC complexity for each respective mechanism. Finally, we propose an architecture integrating modular microfluidic flow control components and OoC devices on a single platform. We emphasize the need for miniaturization of flow control components to achieve portability, minimize sample usage, minimize dead volume, improve the flowing time of fluids to the OoC cell chamber, and enable long-duration experiments.

Being one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strategy to effectively enrich CTCs from whole blood based on size, utilizing a spiral microfluidic channel embedded with a hydrofoil structure at the downstream of the spiral channel. The hydrofoil increases the distance between the streams of CTCs and peripheral blood cells, which are already distributed about two focal axes by the spiral channel, thereby improving the resolution of the separation. Analytical validation of the system has been carried out using Michigan Cancer Foundation-7 (MCF7) breast cancer cell lines spiked into blood samples from healthy donors, and the performance of the system in terms of white blood cell (WBC) depletion, CTC recovery rate and cell viability has been shown in single or two-step process: by passing the sample once or twice through the microfluidic chip. Single step process yielded high recovery (77.1%), viable (84.7%) CTCs. When the collected cell suspension is re-processed by the same chip, recovery decreases to 65.5%, while the WBC depletion increases to 88.3%, improving the purity. Cell viability of >80% was preserved after two-step process. The novel microfluidic chip is a good candidate for CTC isolation applications requiring high recovery rate and viability, including functional downstream analyses for variety of cancer types.