white paper: control under pressure. how to use pneumatic ... · • the benefits of using pressure...

This white paper provides information on:

• The benefits of using pressure to dispense fluids in lab automation• The basic elements of a pressure-controlled dispensing system• Design considerations when using pressurized systems• A look at some of the systems and products in place today

White paper: Control Under Pressure.How to use pneumatic technology to build high-performance liquid dispensing systems for lab automation applications

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© Copyright 2019, Festo AG & Co. KGWhite Paper “Control Under Pressure”

From in vitro diagnostics to pharmaceuticals, many biomedical and life science applications depend on precise, repeatable liquid handling. Oftentimes, these processes involve dispensing nanoliter-scale fluid volumes into hundreds of microplates—some of which contain up to 1,536 wells each. Under these conditions, manual pipetting is imprecise at best and unachievable in high-throughput applications. And while automated liquid handling robots overcome this challenge, they often include unnecessary features and often come with a hefty price tag.

Fortunately, you have another option. Pressure-controlled liquid dispensing systems provide a simple, quick and cost-effective way to dose nanoliter- to milliliter-scale volumes of fluid with precision, reliability and scalability. In this white paper, we’ll explore the basics of designing a pressurized dispensing system—including how to manage flow, pressure and other control variables to optimize your throughput in these critical applications.

VTOE-8 in the lab

The Benefits of Pressure-Based Liquid Handling Systems

• Small doses—starting at 0.25 µl• Lower cost• Fewer moving parts• Easy to clean, maintain and calibrate• High speed—constant flow pressure improves performance over piston systems• Open loop CVs under 3% are commonly achieved, with CVs under 0.01% possible in closed loop,

gravimetric feedback systems

Executive summary

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Introduction

From in vitro diagnostics to pharmaceuticals, many biomedical and life science applications depend on precise, repeatable liquid handling. Oftentimes, these processes involve dispensing nanoliter-scale fluid volumes into hundreds of microplates—some of which contain up to 1,536 wells each. Under these conditions, manual pipetting is imprecise at best and difficult-to-impossible in high-throughput applications. And while automated liquid handling robots overcome this challenge, they often include unnecessary features and come with a hefty price tag.

Fortunately, you have another option. Pressure-controlled liquid dispensing systems provide a simple, quick and cost-effective way to dose nanoliter- to milliliter-scale volumes of fluid with precision, reliability and scalability. In this white paper, we’ll explore the basics of designing a pressurized dispensing system—including how to manage flow, pressure and other control variables to optimize your throughput in these critical applications.

Liquid Control Challenges

The ability to control, regulate and measure small liquid volumes is essential to a variety of biomedical, life science and other lab automation processes—from reagent dosing to sample handling. In these industries, precision is key. In a drug discovery application, for example, a dosing error of only a few percent could render a potential cure ineffective or toxic.

At the same time, delivering liquid samples into microplates and other small vessels comes with its share of challenges. For one, fluid properties and compositions vary widely. For example, viscosities can range from as thin as alcohol to as thick as honey. Fluids can also be highly corrosive, acidic or basic. To complicate things further, these fluid properties can change depending on temperature, dispensing speed, applied pressure and other variables. In addition, dosing these costly, sometimes highly reactive liquids often requires elaborate cleaning procedures between batches to minimize contamination and clogging of wetted parts—further driving up your costs and downtime.

Pressure Controller Safety Valve

Dosing Head

Liquid Reservoir

Balance

Nozzle

Manifold

2/2 Valve

TableThe components in a pressure-operated liquid dispensing system.

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VTOE Dispense Heads Achieve Unparalleled Precision

Festo VTOE pre-assembled dispense heads consist of a manifold, 2/2 valve, dispenser nozzle and tubing connector. This family is available with a transparent polycarbonate (PC) channel plate, as well as a media-resistant channel plate made from polyether ether ketone (PEEK) for applications involving aggressive media. You can mount up to 12 dispense heads on a single rail—enabling different fluids and aliquot volumes to be dosed in parallel. Dosing needle IDs are available in 0.32, 0.6 and 1.0 mm.

VTOE dispense heads achieve high precision when working with small fluid volumes. As indicated by gravimetric tests, the head’s

dispense behavior achieves high linearity over a wide range of impulse times—

indicating high precision with a

coefficient of variation (CV) < 1% from 10–1,000 µl. Figure 1 displays these results for a VTOE dosing

head with a 0.6-mm ID nozzle.

VTOE Dispense Head

Pressure controlled liquid dispensing systems have unique design flexibility to help help you overcome these challenges—enabling you to precisely dose a variety of fluids with exceptionally high throughput.

Pressurized Systems: Setup and Design Considerations

Mechanically simple, pressure-operated liquid dispensing systems require a minimum number of components. A pressure regulator, paired with a safety valve, pressurizes the reservoir containing the liquid. This pressure then drives the liquid through the tubing and solenoid dispense valve. Finally, the nozzle dispenses the liquid into the vessel via a needle tip with a calibrated orifice.

When designing your own pressure-based system, it’s important to keep the following three considerations in mind—all of which will affect the quantity and quality of your doses:

Flow resistance. Your system’s flow rate is defined by the pressure, as well as the overall resistance of the fluid path. This resistance depends on a number of variables, including the tube’s inner diameter (ID), length, dispense valve geometry and fittings.

The most important variable affecting flow is the dispense tip. Working tips—also referred to as channels—can include stationary equipment, such as tubes or hypodermic needles. They can also be disposable in nature or made from metal or plastic. Systems with multiple tips speed up the transfer of liquids by simultaneously aspirating or dispensing fluids into multiple corresponding containers.

In pressurized systems, the tip size directly affects the velocity of dispensed liquids. Unlike pressure and time—which you can control and modify via software—you’ll need to select the right tip prior to deploying your system. In general, smaller tips achieve the best velocity. Festo, for example, uses needle tips with standard IDs between -0.3 and 1 mm. This range works well for most aqueous fluids and dispense volumes from under 1 to 1,000 µl or more. Depending on your application, we can also develop special tips.

In addition, it’s important for your system’s upstream components to achieve higher flows—maximizing your ability to control dosing speeds and pressure at the tip. At Festo, we typically use 2-mm ID tubing, as well as valve and manifold internal passages over 1.5 mm. These sizes work well with our standard range of needles and disposable pipette tips.

VEAB Pressure Regulators

Designed specifically for applications requiring low pressure, the Festo VEAB series provides noiseless, reliable pressure regulation from -1 to 6 bar. These three-way proportional regulators also achieve flow rates up to 20 l/min.

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Figure 1: The gravimetric results of a VTOE dosing head with a 0.6-mm ID dispense tip.

Pressure has a significant effect on dosing volumes and—more importantly—helps control the velocity of the fluid as it passes through the dispense tip. You can generate pressure in several ways, including utilizing an external gas source, like nitrogen, for example, or a compressor to pump air into the closed liquid reservoir. Although pressurized systems can create safety issues, the pressure ranges found in lab automation dispense systems are generally low—only 100–250 millibars. At the same time, it’s important to have safety measures in place that can relieve the pressure in the event of a leak or other technical failure.

Along with the tip size, you can use pressure to control for fluid viscosities—achieving clean, splash-free dispenses.

Dispense time. In pressure dispensing systems, the solenoid valve controls the dispense quantities. The primary factor influencing the volume of dispensed fluids is the valve’s cycle time—allowing you, in theory, to calibrate the timing of the valve according to specific dispense volumes. Because your system’s dispensing performance relies on the valve’s response time, it’s important to choose your solenoid valve carefully: valves with short, highly repeatable response times offer much better dispense precision at higher speeds. Bear in mind, too, that solenoids generate energy when open, and their performance often changes as they warm up. Operating a higher-flow valve for shorter durations reduces this heat but requires a valve with excellent repeatability.

A good rule of thumb is to avoid unnecessary heat generation and very short open times, which also have an effect on dispense performance. Unfortunately, these two objectives can work against each other: smaller valves generate less power but have to remain open for longer periods of time to pass the same volume as larger valves—and vice versa. But the good news is there are ways around this. Using electronics, for example, it’s possible to open a larger valve with a short, high-current pulse—reducing the current before the valve passes heat into the system. Festo builds this control technology into many of our isolation valves. For applications requiring a unique dispense valve, we also manufacture multi-channel current control modules for use with any solenoid.

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Scaling Up: Multi-Head Dispense Systems

Because many lab processes involve liquid control and handling, automating these processes will lead to significant improvements in productivity. One of the biggest benefits to pressure-based dispense systems is their scalability. For example, you can easily combine individual dispense heads—either by mounting them on a rail or retaining plate—to create multi-channel dispense heads that handle different aliquot volumes, fluids and pressures. You can even dispense fluids with different classes by mounting multi-channel dispense heads on an electric axis—creating a planar surface gantry system. Ideal for preparing samples or adding fluids to microplates, these systems maximize your working space and improve throughput without breaking the bank.

When it comes to multi-channel systems, however, keep in mind that small differences among the inlets, valves and nozzles can cause some channels to dispense higher volumes than others—leading to intrinsic tip-to-tip variability on the order of 4%. At resolutions of 1 ms or higher, it’s difficult to compensate for these small variations using whatever processor is controlling the solenoid dose time. A better course of action is to calibrate the separate channels by varying the pull-in and hold-in solenoid current so that all channels dispense the same quantity using the same dispense times. Festo makes this easy with the VAEM valve control module, which utilizes user-friendly software to reduce the tip-to-tip variability to less than 1% in most cases.

According to photometric analysis tests of our VTOE-8 multi-head dispensing system, adjusting the impulse time on each individual channel reduces tip-to-tip variability from 4–1% (left to right images, respectively).

VTOE-8 Multi-Channel Dosing

You can combine our single-channel VTOE dispense heads

to create 8-channel liquid dispensing systems. Ideal for

manufacturing dilutions, nutrient solutions and dispensing

reagents, this multi-channel system lets you dose

different fluids and fill microplate wells in parallel. At the

same time, the ability to control each valve individually

closes the gap on tip-to-tip variability—maximizing your

dosing precision.

VTOE-8 Multi- Channel Dispense Head

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VAEM Offers Precision Valve Control

Easy to integrate into your dispensing system, our VAEM valve control module allows you to preset and

calibrate the parameters of your solenoid valve, including setting peak/hold currents and actuation

times with 0.2-ms resolution. Control up to eight valves individually by sending

commands via RS-232, Modbus TCP Ethernet or IO-Link digital interfaces. It also

includes a graphical user interface and external trigger.

VAEM Module

Conclusion

Pressurized liquid dispensing systems can help you optimize your throughput in lab automation applications by providing a mechanically simple, cost-effective way to dose nanoliter-scale fluid volumes with speed, precision and reliability. These systems easily meet criteria related to flow, pressure and other control variables while offering scalability—enabling you to easily build higher-level liquid handling systems at a fraction of the cost of complex robotics.

From single-channel dispense systems, to motion control solutions, we can combine and scale our standard products—including pressure regulators, tubing, kinematics and controllers—to create liquid handling systems tailored to your specific needs. From start to finish, our life sciences experts stand ready to support your lab automation needs—no matter how technically challenging.

To learn more about our liquid handling capabilities, visit: www.festo.com

white paper: control under pressure. how to use pneumatic ... · • the benefits of using pressure...

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