In their latest publication, a team from the laboratory of Mohammad A. Qasaimeh, at New York University Abu Dhabi, set a new milestone for open space microfluidics in the field of cell biology. The researchers developed a new kind of open-space microfluidic system for the sequential cell separation and patterning based on dielectrophoresis, and are able to reach a cell purity of ~90 %.

The syringe pumps were used to generate flow from the injection to aspiration aperture of their device, in order to generate a hydrodynamic flow confinement within which cell separation occurred.

Laboratory Setup:

For the research work it was necessary to use specially developed and 3D-printed microfluidic chips. Based on the Hele-Shaw-cell approximation, the flow was generated between two parallel flat plates by simultaneous injection and aspiration of fluids from the microelectrofluidic probe. Dielectrophoresis forces were then used to isolate target cells out of the flow stream and sequentially pattern them on the bottom substrate. Based on this method, cell purity of up to ~90 % was reached, characterized by fluorescence microscopy.

With their publication in Lab on a Chip last year, Qasaimeh et al. provide new tools to separate specific cells from heterogeneous cell population without need of any microchannels and have thus laid important foundations for this field of research.

Laboratory setup cell separation

The setup for the investigation of open space microfluidics for cell separation could be realized with a modular and high-precision CETONI dosing system. In order to generate continuous multipoles to separate cells with a high isolation efficiency, an extremely uniform and pulsation-free fluid flow is required. The nemesys precision syringe pumps are ideally suited for precise and smooth dosing of smallest fluid quantities. Thanks to its modularity, the setup can also be extended at any time, giving the research team complete flexibility in their work.

Used CETONI devices:

• Base 120
• 6x CETONI nemesys Low Pressure Syringe Pumps 290N

Literature:
A. T. Brimmo, A. Menacherya, M. A. Qasaimeh: Microelectrofluidic probe for sequential cell separation and patterning. 2019, (19), 4052-4063. DOI: 10.1039/C9LC00748B

Gold nanoparticles have recently become very important in different application fields. The reproducible synthesis of such nanoparticle is quite difficult due to many reaction parameters, which affect the optical and electrical properties of the particles. The size, shape and dispersity can also affect these properties.

Chow et al. In their scientific article Chow et al. report about a new flow-controlled method for the synthesis of gold nanoparticles using a liquid-liquid membrane-based separation technology.

Laboratory Setup

The flow-controlled synthesis of nanoparticles has a lot of convincing advantages. Mainly because of the precise control of the reaction parameters and surrounding conditions, i.e. mixing ratio, residence times and temperatures. Finally, flow-controlled synthesis minimizes batch-to-batch variability while benefitting yield and quality of the gold nanoparticles.

In the article Chow et al. describe a flow-controlled study for the synthesis of DMAP stabilized gold nanoparticles split into 3 synthesis stages. Based on the modular neMESYS syringe pump system and CETONI’s automation software QmixElements, a novel flow setup for the gold nanoparticle synthesis could be realized. A setup of six CETONI neMESYS Mid Pressure syringe pumps were used to generate the exact and pulsation-free flow stream to allow the formation of TOAB-Au stabilized nanoparticles using sodium borohydride as a reducing agent. In addition, a modular peristaltic pump (peRISYS-S, CETONI) was used to deliver three lines of solution for the washing of TOAB-Au stabilized nanoparticles in a 2 m mixing coil. For effective diffusion and advective mixing a glass-silicon split and recombine KombiMix micromixer (CETONI) was used in the third stage.

To separate the organic and aqueous phases a liquid-liquid membrane has been used, too. In order to balance the pressure on both sides for an efficient separation, precise pressure measurements are essential. CETONI’S pressure module QmixP was used to monitor any pressure-build up upstream due to nanoparticle aggregation which may cause a blockage of the T-mixer.

Within the scope of this brilliant research work a liquid-liquid membrane-based separation of gold nanoparticles could be demonstrated for the first time. A versatile and easy-to-use software tool in combination with various off-the-shelf plug and play components (neMESYS syringe pumps, peRISYS-S peristaltic pump, pressure measurement module etc.) from a single source had a decisive influence on the research progresses and success.

Used CETONI devices:

• Base 600
• Syringe pumps: 6x neMESYS Mid Pressure modules 1000N
• Peristaltic pump: 1x peRISYS-S
• Pressure controller: 1x QmixP
• Micromixer: KombiMix
• Software: CETONI Elements (QmixElements)

Literature:
Chow E., Raguse B., Della Gaspera E., Barrow S. J., Hong J., Hubble L. J., Chai R., Cooper J. S., Sosa Pintos A., Flow-controlled synthesis of gold nanoparticles in a biphasic system with inline liquid–liquid separation. React. Chem. Eng., 2020, 5, 356. DOI: 10.1039/c9re00403c

In their latest publication, a team from the laboratory of Thomas Gervais, at École Polytechnique de Montréal set the foundations of “microfluidic multipoles”, a new kind of open-space microfluidic systems. The experimental demonstration of the principles exposed required the use of up to 12 Low Pressure Syringe Pumps neMESYS 290N. The pumps powered microfluidic multipoles were further used to automate an immunofluorescence assay on an antibody array.

Laboratory Setup

Specially developed and 3D-printed sample heads were used, which were positioned in close proximity with the surface to be processed. By simultaneous injection and aspiration of fluids from the numerous apertures, periodic patterns of confined reagents could be formed on the surface. The flow under these devices could be modeled by using a direct analogy with electromagnetic theory (so-called multipoles). Under this analogy, the neMESYS pumps impose a flow rate which is analogous to a constant charge in an electrostatic field. The flow streamlines generated are, in turn, mathematically analogous to the electric field distribution around charges and can be modeled easily. By using the fluorescent dyes, the patterns could be further visualized and analyzed by fluorescence microscopy.

With their publication in Nature Communications this year, Goyette, Boulais, et al. provide new tools to design and perform surface processing and biological assays to further the development of open-space microfluidics. The setup for the investigation of multipoles could be realized with a modular and high-precision CETONI dosing system. In order to generate continuous multipoles with sub-millimetre accuracy while minimizing reagent consumption, an extremely uniform and pulsation-free fluid flow is required. The neMESYS precision syringe pumps are ideally suited for precise dosing of smallest fluid quantities.

Microfluidic multipoles

The PID-regulated drive unit of the syringe pump ensures an extremely even drive of the syringe piston, prevents stick-slip effects and thus guarantees the high accuracy and pulsation-free flow of the generated fluid, which was a prerequisite for this application. Due to the modularity, the setup can also be extended at any time.

Used CETONI devices:

• Base 120
• 12 x neMESYS Low Pressure module 290N

Literature:

Goyette P.-A., Boulais E., Normandeau F., Laberge G., Juncker D., Gervais T. Microfluidic multipoles theory and applications. Nature Communications. 2019, (10), 1781. DOI: 10.1038/s41467-019-09740-7

Postek et al. demonstrated an automated high-throughput screening for MIC determination (minimal inhibitory concentration) of an antibiotic in nanolitre droplets for different E.coli concentrations. With the help of the specially developed DropChop chip, different physically separated compartments can be generated. With the resulting ultra-small sample volumes, comprehensive test series can subsequently be carried out with maximum efficiency and large scaling.

Laboratory Setup

In this study, µl-volume droplets of different E.coli dilutions were automatically generated by neMESYS syringe pumps in combination with the versatile rotAXYS miniature positioning system. These µl-volume droplets were then transferred into nL-volume droplets within a compartment using the DropChop chip, which was specially developed for this specific application, then cultured and subsequently comprehensively analyzed using fluorescence microscopy.

This application illustrates the advantages of the CETONI product philosophy: Thanks to the modular system design, various devices could be combined effortlessly and integrated easily into the customer’s software environment via the practical CETONI software development kit. The precisely controllable rotAXYS facilitated the fully automated and precise processing of µl-volume droplets by the neMESYS syringe pump system from a 96-well microtiter plate. The reproducible generation of these uniform small droplets was mainly achieved by the interruption-free motion characteristics of the neMESYS syringe pumps, while the physical separation of subsequent emulsions was achieved with the easy programming of the pump protocol of operations with the Qmix software.

The CETONI system also easily met the requirements of a sterile working environment with the right accessories.

Used CETONI devices:

• Base 120
• 3 x Low Pressure Syringe Pump neMESYS 290N
• Compact Positioning System rotAXYS

Literature:

Postek W., Gargulinski P., Scheler O., Kaminski T. , Garstecki P. Microfluidic screening of antibiotic susceptibility at a single-cell level shows the inoculum effect of cefotaxime on E. coli

A new versatile computer-controlled gustometer has recently been described Andersen et al. The device was built to match the specific needs of scientists running behavioral, electrophysiologal, and hemodynamic investigations.

Hardware

Laboratory Setup

The research group of Dr. Kathrin Ohla, hosted at the Institute of Neuroscience and Medicine 3 at Research Center Jülich, developed an affordable gustometer suitable for various experiments in taste research. The setup mainly consists of several low-pressure pumps neMESYS 290N for dosing of liquid taste solutions directly onto the participants’ tongues.

Andersen et al. employed a mouth piece that was mostly built from off-the-shelf components, allowing for an independent stimulation of the left and right side of the tongue (Fig. 3). In their particular investigation, de-ionized water was delivered to one or both sides of the tongue; 18 participants reported the perceived stimulation side. To test whether the stimulation system is suitable for electrophysiological investigations with a high temporal precision (in the milli-second range), some participants were repeatedly stimulated with a taste stimulus (sodium chloride solution) while brain activity was recorded using electroencephalography (EEG). Data analysis in fact revealed neural activation evoked by the taste stimulation. The flow rate was 1 ml/s, and automated dosing and refill cycles were enabled with the help of a computer-controlled 3/2 solenoid valve (3 connectors, 1/4”-28 UNF thread).

 

A necessary requirement in the investigation was precise and pulsation-free stimulus delivery, combined with high reproducibility – key features of our neMESYS syringe pump technology. Further, the modularized setup is easy to extend and can be adjusted to meet new demands of future experiments; it also makes cleaning and replacement of individual components easy to comply with the high standards of hygiene, which is required in taste research.

Software

The research team implemented a pump control interface in Python based on the CETONI Qmix Software Development Kit (SDK). This pyqmix package uses the Qmix SDK libraries (DLLs) and exposes the hardware interface via object-oriented Python code. The package was published under a free and open-source license and is available from GitHub. All interested users of our SDK may also use this Python package and adjust it to their needs. It is, therefore, a second option for using Python alongside CETONI’s official Python interface.

The following table provides a short comparison between both Python interfaces:

	CETONI Qmix SDK for Python	pyqmix
C call interface	ctypes	cffi
Supported devices	Pumps Valves I/O Interfaces Controllers Motion Control Devices	Pumps Valves
Installation	Zip Archive	Via pip (PyPI) or conda (conda-forge), contained in PsychoPy (standalone)
PsychoPy-Integration	no	yes
License	Modified BSD License	GPL 3.0
GitHub Repository	https://github.com/CETONI-Software/qmixsdk-for-python	https://github.com/psyfood/pyqmix
Online documentation	QmixSDK_Python.html	https://pyqmix.readthedocs.io

The following code snippet demonstrates how a pump can be operated via pyqmix:

from pyqmix import QmixBus, QmixPump, config
import time

# Specify the QmixELements configuration
config.set_qmix_config('qmix_config')

# Initialize the first pump
bus = QmixBus()
pump = QmixPump(index=0)
pump.set_flow_unit(prefix='milli', volume_unit='litres', time_unit='per_second')
pump.set_volume_unit(prefix='milli', unit='litres')
pump.set_syringe_params_by_type(syringe_type='50 ml glass')

# Fill the syringe
pump.generate_flow(-0.5, wait_until_done=True)

# Dispense 10x every 2 sec
for i in range(10):
    pump.dispense(volume=1, flow_rate=1, wait_until_done=True, switch_valve_when_done=True)
    time.sleep(2)

 

Andersen et al. also developed a remote control interface based on pyqmix, named pyqmix-web, allowing the user to control the pumps from within a web browser: Therefore, the user can control the gustometer via a graphical interface in the browser, i.e. remotely.

This simple graphical interface also makes it possible to operate the pumps via a touchscreen, like an iPad or smartphone. Again, this software is provided under a free license and can be downloaded from the respective GitHub repository.

Lastly, PsychoPy, a popular free and open-source software for conducting psychological and neuroscientific experiments, offers integration of pyqmix, thereby further simplifying the use of syringe pumps in neuroscientific studies:

Summary

A compact, computer-controlled setup for precise and reproducible delivery of liquid taste stimuli has been developed. The system is suitable for electrophysiological investigations. The high precision of the neMESYS syringe pumps, combined with an elaborated setup, allowed the researchers to present taste stimuli with high precision and reproducibility. This versatile gustometer can be used to deliver multiple stimuli independently. Further, a Python (remote) control interface was developed based on the CETONI Software Development Kit (Qmix SDK), even allowing pump operation from a touchscreen-based device like an iPad or phone.

Used CETONI devices:

• Base Module BASE 120
• 5 x low-pressure syringe pumps neMESYS 290N
• Qmix SDK

Literature:

Andersen C., Alfine L., Ohla K., Höchenberger R.: A new gustometer: Template for the construction of a portable and modular stimulator for taste and lingual touch. Behavior Research Methods, 2018:1-15. DOI: 10.3758/s13428-018-1145-1

In a recent publication, Peschke et al. successfully realized microfluidic biocatalytic cascades in a compartmentalized microfluidic chip with excellent stereoselectivities.

Laboratory Setup

In this experimental set-up, different substrates and cofactors solutions were placed in neMESYS low pressure syringe pumps and perfused through a four-channel PMMA microchip, which is loaded with enzymes immobilized on magnetic beads at a very low flow rate of 1 µl/min. After a successful enzymatic reaction on the chip, individual samples were taken by the rotAXYS sample handling system for the subsequent quantitative chiral HPLC analysis and characterization of the biocatalytic reaction products.

Altogether, this publication gives a vivid description how CETONI devices can automate a complete application setup from biocatalytical reaction up to the sample collection for the analysis with the usual high precision and extreme accuracy of the neMESYS syringe pumps. The combination of the neMESYS low pressure pumps and the rotAXYS enable a parallelization and fractionation of several experiments at the same time.

Used CETONI devices:

• Base 120
• 7 x Low Pressure Syringe Pump neMESYS 290N
• Compact Positioning System rotAXYS

Literature:

Peschke T., Skoupi M., Burgahn T., Gallus S., Ahmed I., Rabe K. S., Niemeyer Ch.M., Self-Immobilizing Fusion Enzymes for Compartmentalized Biocatalysis. ACS Catalysis 2017 7 (11), 7866-7872; DOI: 10.1021/acscatal.7b02230

We are pleased to announce the first release of the QmixElements software in 2019. With this release we extend the functional range of the CETONI devices by new features, functions and we supplement the software with many useful details or improve existing functions. Highlight of the new QmixElements version v20190108 is the improved graphical user interface with the new Advanced Docking System.

In the previous QmixElements software there was a central area for switching workspaces. Individual tool windows could be freely arranged and moved around this central area. So it was possible to customize the graphical user interface to a limited extent.

However, the individual workspaces displayed in the central area could not be moved and only one workspace was visible at a time. For example, one could work either in the user interface of the neMESYS pumps, or in the positioning map for the rotAXYS or one could show the graphical logger. A simultaneous display was not possible up to now.

Dock everywhere – no central widget

In the new QmixElements software this limitation no longer exists. Due to the new advanced docking system there is no longer a central workspace, but only single views (windows) which can be positioned freely in the graphical user interface or can be detached from it.

You can dock all views at any edge of the main window or in any other view – so you can dock virtually anywhere and move any view to any position. Markers make it easy to see where you can insert a view.

Detach views as separate windows – perfect for multi-monitor use

Not only can you move all views to new positions in the main window, but you can also detach the individual views completely from the application window and move them as a stand-alone window. This allows you, for example, to move each individual view to a different monitor. This ensures that you always keep an eye on important information and make optimum use of the available screen space.

Individual views can be “docked” to any position not only in the main window of the application, but in every window and every individual view of the application. This allows you to distribute all views across multiple windows or even across multiple monitors.

Moving Multiple Views Simultaneously

You can not only move individual views and detach them from the user interface, but also complete view groups. If you have grouped several views in tabs, you can remove the entire view group by clicking on the title bar of the group and pulling it out of its position. This allows you to quickly customize even complex layouts.

Perspectives – fast switching of the entire user interface

A certain layout of views that is perfectly suited for a particular application or user may be less suited for other tasks or other users. The new graphical user interface helps you to switch the complete layout with just one mouse click and to completely change the arrangement of views and windows in a second. The software offers so-called “perspectives” for this purpose. A perspective is nothing more than a certain layout of views with a fixed name. This means that if you have found the perfect configuration of views for a certain task, simply save this configuration under a name as a perspective.

Other perspectives can be created for other tasks and other users. Later, you can simply select a perspective from the perspective menu to quickly switch the interface layout for a new task.

The video on our youtube channel gives you a first impression of what is possible with the new advanced docking system of the QmixElements software.

In their scientific article report, Kashyap et al. from the team of Dr. Govind Kaigala at IBM Research Zurich describes a new method for local lysis of living adherent cells within a microfluidic probe for genomic and transcription profiling.

Laboratory Setup

A microfluidic probe was used for the local analysis of biological samples (e.g. co-cultures). To realize the microscale confinement of biochemicals, a simultaneous injection and aspiration process was applied — hydrodynamic flow confinement (HFC). The liquid-handling process was implemented using 4 neMESYS Low Pressure Syringe Pumps. Large lysate volumes (> 100 µl) were directly collected within the syringes associated with the corresponding aspiration pumps. Small volumes (< 10 µL) were collected at the microfluidic probe head using an additional neMESYS Low Pressure Syringe Pump and then injected into a PCR tube. Intermediate lysate volumes (≈ 50 µL) were extracted into sampling loops using a Qmix V Valve module.

In summary, based on the modular neMESYS syringe pump system and features of automation software QmixElements, a novel setup for cell lysis and sample collection could be realized. Overall, 5 pumps providing the necessary injection and aspiration of independent streams of various reagents enabled continuous lysis to generate highly concentrated lysates for DNA analysis. In addition to the microfluidic probe and periphery (motorized xyz stages, microscope), the neMESYS system characterized by reliable precision and pulsation-free flow in combination with the versatile control software, is ideal for this customer application.

Used CETONI products:

• Cableset BASE120
• 5 x Low Pressure Syringe Pump neMESYS 290N
• Low Pressure Valve Qmix V EX
• QmixElements software

Literature:

Kashyap A., Autebert J., Delamarche E., Kaigala G. V., Selective local lysis and sampling of live cells for nucleic acid analysis using a microfluidic probe. Sci Rep 2016, 6 (29579). DOI: 10.1038/srep29579

Fabricius et al. Fabricius et al. reported in their scientific article on an automated sample collection system (micro profiling and micro sampling system- missy) for the spatial high resolution investigation of water samples from water saturated boundary layers with small volumes of < 500 µl (sediments, biofilms or soils).

Laboratory Setup

After sample collection, the water sample was pumped via the neMESYS Low Pressure Syringe Pump through the Qmix V EX valve module (multiport valve) and transferred into a 96-well plate via the compact 3D-positioning system rotAXYS. Conducting a chemical characterization of the samples, like e.g., multielement analyses, insight into the conditions and processes in the sediment at a small scale can be obtained.

In summary, a setup for sample collection was developed by using the CETONI devices, which enables a continuous sampling at water saturated boundary layers at a millimetre scale. Our modular neMESYS syringe pumps offers an extremely precise and stable flow with no pulsation in ranges from picolitres to millilitres per second or for the high-precision dosing of smallest fluid quantities up to continuous dosing on a large scale.

Used CETONI products:

• Base Module BASE 120
• Low Pressure Syringe Pump neMESYS 290N
• Low Pressure Valve Qmix V EX
• Compact Positioning System rotAXYS
• QmixElements software

Literature:

Fabricius A.-L., Duester L., Ecker D., Ternes T.-A. New Microprofiling and Micro Sampling System for Water Saturated Environmental Boundary Layers. Environ. Si. Technol. 2014, 48 (14), 8053-61. DOI: 10.1021/es501814b