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Intestinal organoids are 3D cell structures that replicate some aspects of organ function and are organized with a polarized epithelium facing a central lumen. To enable more applications, new technologies are needed to access the luminal cavity and apical cell surface of organoids. We developed a perfusion system utilizing a double-barrel glass capillary with a pressure-based pump to access and modify the luminal contents of a human intestinal organoid for extended periods of time while applying cyclic cellular strain. Cyclic injection and withdrawal of fluorescent FITC-Dextran coupled with real-time measurement of fluorescence intensity showed discrete changes of intensity correlating with perfusion cycles. The perfusion system was also used to modify the lumen of organoids injected with GFP-expressing E. coli. Due to the low concentration and fluorescence of the E. coli, a novel imaging analysis method utilizing bacteria enumeration and image flattening was developed to monitor E. coli within the organoid. Collectively, this work shows that a double-barrel perfusion system provides constant luminal access and allows regulation of luminal contents and luminal mixing.

In this study, a valveless pump was successfully designed and fabricated for the purpose of medium transportation. Different from traditional pumps, the newly designed pump utilizes an actuated or a deflected membrane, and it serves as the function of a check valve at the same time. For achieving the valveless property, an inlet or outlet port positioned in an upper- or lower-layer thin membrane was designed to be connected to an entrance or exit channel. Theoretical analysis and numerical simulation were conducted simultaneously to investigate the large deformation characteristics of the membranes and to determine the proper location of the inlet or outlet port on the proposed pump. Then, the valveless pump was fabricated on the basis of the proposed design. In the experiment, the maximum flow rate of the proposed pump exceeded 12.47 mL/min at a driving frequency of 5.0 Hz and driving pressure of 68.95 kPa.

This paper introduces the synchronous micromotor concept and presents new investigations on its application as an integrated driving mechanism in microfluidic systems. A spiral channel viscous micropump and a microstirrer are considered and tested as examples to verify the concept. The fabrication technology of such integrated systems is based on UV depth lithography, electroplating and soft lithography. The synchronous micromotor consists of a stator including double layer coils, and a rotor disk containing alternate permanent magnets. The coils are distributed evenly around the stator and arranged in three phases. The phases are excited by sinusoidal currents with a corresponding phase shift resulting in a rotating magnetic field. Regarding the spiral channel viscous micropump, a spiral disk was fixed onto the rotor disk and run at different rotational speeds. Tests showed very promising results, with a flow rate up to 1023 µL·min−1 at a motor rotational speed of 4500 rpm. Furthermore, for the application of a microstirred-tank bioreactor, the rotor disk design was modified to work as a stirrer. The performance of the developed microbioreactor was tested over a time period of approximately 10 h under constant stirring. Tests demonstrated the successful cultivation of S. cerevisiae through the integration of the microstirrer in a microbioreactor system. These systems prove that synchronous micromotors are well suited to serve as integrated driving mechanisms of active microfluidic components.

The flow of liquids in centrifugal microfluidics is unidirectional and dominated by centrifugal and Coriolis forces (i.e., effective only at T-junctions). Developing mechanisms and discovering efficient techniques to propel liquids in any direction other than the direction of the centrifugal force has been the subject of a large number of studies. The capillary force attained by specific surface treatments, pneumatic energy, active and passive flow reciprocation and Euler force have been previously introduced in order to manipulate the liquid flow and push it against the centrifugal force. Here, as a new method, the moment of inertia of the liquid inside a chamber in a centrifugal microfluidic platform is employed to manipulate the flow and propel the liquid passively towards the disc center. Furthermore, the effect of the moment of inertia on the liquid in a rectangular chamber is evaluated, both in theory and experiments, and the optimum geometry is defined. As an application of the introduced method, the moment of inertia of the liquid is used in order to mix two different dyed deionized (DI) waters; the mixing efficiency is evaluated and compared to similar mixing techniques. The results show the potential of the presented method for pumping liquids radially inward with relatively high flow rates (up to 23 mm³/s) and also efficient mixing in centrifugal microfluidic platforms. [ABSTRACT FROM AUTHOR]

This paper presents an integrated digitally controllable microfluidic system for continuous solution supply with a real-time concentration control. This system contains multiple independently operating mixing modules, each integrated with two vortex micropumps, two Tesla valves and a micromixer. The interior surface of the system is made of biocompatible materials using a polymer micro-fabrication process and thus its operation can be applied to chemicals and bio-reagents. In each module, pumping of fluid is achieved by the vortex micropump working with the rotation of a micro-impeller. The downstream fluid mixing is based on mechanical vibrations driven by a lead zirconate titanate ceramic diaphragm actuator located below the mixing chamber. We have conducted experiments to prove that the addition of the micro-pillar structures to the mixing chamber further improves the mixing performance. We also developed a computer-controlled automated driver system to control the real-time fluid mixing and concentration regulation with the mixing module array. This research demonstrates the integration of digitally controllable polymer-based microfluidic modules as a fully functional system, which has great potential in the automation of many bio-fluid handling processes in bio-related applications.

The flow of liquids in centrifugal microfluidics is unidirectional and dominated by centrifugal and Coriolis forces (i.e., effective only at T-junctions). Developing mechanisms and discovering efficient techniques to propel liquids in any direction other than the direction of the centrifugal force has been the subject of a large number of studies. The capillary force attained by specific surface treatments, pneumatic energy, active and passive flow reciprocation and Euler force have been previously introduced in order to manipulate the liquid flow and push it against the centrifugal force. Here, as a new method, the moment of inertia of the liquid inside a chamber in a centrifugal microfluidic platform is employed to manipulate the flow and propel the liquid passively towards the disc center. Furthermore, the effect of the moment of inertia on the liquid in a rectangular chamber is evaluated, both in theory and experiments, and the optimum geometry is defined. As an application of the introduced method, the moment of inertia of the liquid is used in order to mix two different dyed deionized (DI) waters; the mixing efficiency is evaluated and compared to similar mixing techniques. The results show the potential of the presented method for pumping liquids radially inward with relatively high flow rates (up to 23 mm3/s) and also efficient mixing in centrifugal microfluidic platforms.

This paper introduces the synchronous micromotor concept and presents new investigations on its application as an integrated driving mechanism in microfluidic systems. A spiral channel viscous micropump and a microstirrer are considered and tested as examples to verify the concept. The fabrication technology of such integrated systems is based on UV depth lithography, electroplating and soft lithography. The synchronous micromotor consists of a stator including double layer coils, and a rotor disk containing alternate permanent magnets. The coils are distributed evenly around the stator and arranged in three phases. The phases are excited by sinusoidal currents with a corresponding phase shift resulting in a rotating magnetic field. Regarding the spiral channel viscous micropump, a spiral disk was fixed onto the rotor disk and run at different rotational speeds. Tests showed very promising results, with a flow rate up to 1023 µ⋅L-min-1 at a motor rotational speed of 4500 rpm. Furthermore, for the application of a microstirred-tank bioreactor, the rotor disk design was modified to work as a stirrer. The performance of the developed microbioreactor was tested over a time period of approximately 10 h under constant stirring. Tests demonstrated the successful cultivation of S. cerevisiae through the integration of the microstirrer in a microbioreactor system. These systems prove that synchronous micromotors are well suited to serve as integrated driving mechanisms of active microfluidic components. [ABSTRACT FROM AUTHOR]

This paper presents an integrated digitally controllable microfluidic system for continuous solution supply with a real-time concentration control. This system contains multiple independently operating mixing modules, each integrated with two vortex micropumps, two Tesla valves and a micromixer. The interior surface of the system is made of biocompatible materials using a polymer micro-fabrication process and thus its operation can be applied to chemicals and bio-reagents. In each module, pumping of fluid is achieved by the vortex micropump working with the rotation of a micro-impeller. The downstream fluid mixing is based on mechanical vibrations driven by a lead zirconate titanate ceramic diaphragm actuator located below the mixing chamber. We have conducted experiments to prove that the addition of the micro-pillar structures to the mixing chamber further improves the mixing performance. We also developed a computer-controlled automated driver system to control the real-time fluid mixing and concentration regulation with the mixing module array. This research demonstrates the integration of digitally controllable polymer-based microfluidic modules as a fully functional system, which has great potential in the automation of many bio-fluid handling processes in bio-related applications. [ABSTRACT FROM AUTHOR]

Intestinal organoids are 3D cell structures that replicate some aspects of organ function and are organized with a polarized epithelium facing a central lumen. To enable more applications, new technologies are needed to access the luminal cavity and apical cell surface of organoids. We developed a perfusion system utilizing a double-barrel glass capillary with a pressure-based pump to access and modify the luminal contents of a human intestinal organoid for extended periods of time while applying cyclic cellular strain. Cyclic injection and withdrawal of fluorescent FITC-Dextran coupled with real-time measurement of fluorescence intensity showed discrete changes of intensity correlating with perfusion cycles. The perfusion system was also used to modify the lumen of organoids injected with GFP-expressing E. coli. Due to the low concentration and fluorescence of the E. coli, a novel imaging analysis method utilizing bacteria enumeration and image flattening was developed to monitor E. coli within the organoid. Collectively, this work shows that a double-barrel perfusion system provides constant luminal access and allows regulation of luminal contents and luminal mixing. [ABSTRACT FROM AUTHOR]

In this study, a valveless pump was successfully designed and fabricated for the purpose of medium transportation. Different from traditional pumps, the newly designed pump utilizes an actuated or a deflected membrane, and it serves as the function of a check valve at the same time. For achieving the valveless property, an inlet or outlet port positioned in an upper- or lower-layer thin membrane was designed to be connected to an entrance or exit channel. Theoretical analysis and numerical simulation were conducted simultaneously to investigate the large deformation characteristics of the membranes and to determine the proper location of the inlet or outlet port on the proposed pump. Then, the valveless pump was fabricated on the basis of the proposed design. In the experiment, the maximum flow rate of the proposed pump exceeded 12.47 mL/min at a driving frequency of 5.0 Hz and driving pressure of 68.95 kPa. [ABSTRACT FROM AUTHOR]

In this study, a valveless pump was successfully designed and fabricated for the purpose of medium transportation. Different from traditional pumps, the newly designed pump utilizes an actuated or a deflected membrane, and it serves as the function of a check valve at the same time. For achieving the valveless property, an inlet or outlet port positioned in an upper- or lower-layer thin membrane was designed to be connected to an entrance or exit channel. Theoretical analysis and numerical simulation were conducted simultaneously to investigate the large deformation characteristics of the membranes and to determine the proper location of the inlet or outlet port on the proposed pump. Then, the valveless pump was fabricated on the basis of the proposed design. In the experiment, the maximum flow rate of the proposed pump exceeded 12.47 mL/min at a driving frequency of 5.0 Hz and driving pressure of 68.95 kPa.