white paper: control under pressure. how to use pneumatic

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

2

© Copyright 2020, Festo USWhite 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 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.

Pressure-controlled liquid dispensing systems, shown below, provide a simple, quick, and cost-effective way to dose nanoliter-to milliliter-scale volumes of fluid with precision, reliability, and scalability. This white paper will explore the basics of designing a pressurized dispensing system — including how to manage flow, pressure, and other control variables to optimize throughput in these critical applications.

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

Pressure Controller Safety Valve

Dosing Head

Liquid Reservoir

Balance

Nozzle

Manifold

2/2 Valve

Table

The essential components of a pressure/solenoid based dispense system

3


Microplate based lab automation systems depend on rapid, precise liquid dispensing. Eight-channel systems, shown here, are widely used to reduce dispense time and optimize workflow.

Liquid Control Challenges

The ability to control, regulate, and measure small liquid volumes is essential to many biomedical, life science, and other lab automation processes — from reagent dosing to analytical sample preparation. In these industries, precision can be 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, fluid properties change depending on temperature, dispensing speed, applied pressure, and other variables. In addition, dosing these costly, sometimes highly reactive liquids often requires painstaking cleaning procedures between batches to minimize cross-contamination and clogging of wetted parts — further driving up costs and downtime. Pressure controlled liquid dispensing systems have unique design flexibility to help overcome these challenges and enable precise dosing of a variety of fluids with exceptionally high throughput.

VTOE-8 in the lab

4


VTOE Dispense Heads Achieve Reliable, Repeatable Precision

Festo VTOE pre-assembled dispense heads consist of a manifold, 2/2 valve, dispenser nozzle, and tubing connector. This family of products is available with a wide variety of materials compatible with most liquids used in life science. Up to 12 dispense heads can be mounted 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.

A VTOE dispense head, shown below, achieves high precision when working with small fluid volumes. As indicated by gravimetric tests, the VTOE 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.

VTOE Dispense Head

Pressurized Systems: Setup and Design Considerations

Mechanically simple, pressure-operated liquid dispensing systems require a minimum number of components. A precision regulator, or pump, 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 a pressure-based system, it is important to keep the following three considerations in mind — each of which has a unique impact on the quantity and quality of doses:

Flow resistance. A system’s dispense rate is defined in large part by the pressure, as well as the overall resistance, of the fluid path. This depends on a number of variables, including tubing diameter, length, dispense valve geometry, and fittings. Proper selection of these components at the start of the project has a great impact on the flexibility and precision of the final system. In pressurized systems, the tip size directly affects the velocity of dispensed liquids. Unlike pressure and time — which can be controlled and modified via software — the correct tip needs to be selected prior to deploying the system. In general, smaller tips achieve the best velocity. Festo, for example, uses needle tips with calibrated orifices 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.

In addition, it is important for upstream components to be sized to achieve higher flows—maximizing the system’s ability to control dosing speeds and pressure at the tip. As a guideline, typical systems may use 2-mm ID tubing, with valve and manifold internal passages over 1.5 mm. These sizes work well with commercially available ranges of needles and disposable pipette tips .

5


0 200 400 600 800 900

900

800

700

600

500

400

300

200

100

0

1,8

1,6

1,4

1,2

1

0,8

0,6

0,4

0,2

0

1000

Valve Opening Time, ms

Do

sed

Vo

lum

e,

µl

Volume

Co

eff

icie

nt

of

Va

ria

tio

n (

CV

), %

CV

Dispense time.

The most repeatable and reliable way to control dispense volumes in a pressure- based system is with a solenoid valve at or near the dispense tip. Solenoid valves are highly repeatable, and the relationship between solenoid “on” time and dispense volume becomes linear after the valve fully opens, typically a small fraction of a second.

As an example, the chart below gives the gravimetric results of a solenoid dosing head with a 0.6-mm dispense orifice. CV remains under 1% down to short 50ms valve opening times. Above 50ms the dark blue line shows that dispense time is directly proportional to dose volume, making calibration simple. Changing tip size up or down changes dose volume proportionally. The light blue line indicates how CV remains under 1 percent through a short valve opening time.

Volume/Time Dispense Results(Volume in dark blue, CV in light blue, Opening Time in milliseconds)

A good rule of thumb is to avoid unnecessary heat generation and short open times, which also effect dispense performance. These two objectives can work against each other: smaller valves typically generate less power but have to remain open for longer periods of time to pass the same volume as larger valves and vice versa. The good news is there are ways around this. Using electronics, for example, it is possible to open a larger valve with a short, high-current pulse, reducing the current before the valve passes heat into the system. Some valve manufacturers build this control technology – referred to as spike and hold - into many of their products. For applications requiring a unique dispense valve without this feature, Festo also manufactures multi-channel current control modules for use with any solenoid.

6


Pressure Control

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. Pressure can be generated in several ways, including utilizing an external gas source, like nitrogen, or a compressor to pump air into the closed liquid reservoir. The pressure ranges found in lab automation dispense systems are generally low, only 100-250 millibars, and easy to manage. At the same time, it is important to consider safety measures in place such as a blow off valve that can relieve the pressure in the event of a leak or other technical failure. Along with the tip size, pressure can be used to optimize tip dispense velocity to achieving clean, splash-free dispenses.

Any pressurized system stores energy, which can be problematic in terms of leakage if not considered in the original design. Potential leakage issues will not be a problem, however, in a system that uses appropriate gas and liquid fittings where needed. When feasible, it is best to design the system so pressure is relieved when the system is not in use. This can be accomplished by, using either a switching valve or an electronic regulator that is shut off when power is removed. Source vessels should be rated for the highest working pressure in the system for safety considerations. In lab based liquid dosing systems, pressure is generally very low: under 2-3 PSI. Higher pressure systems can be used to supply, but special care should be taken to ensure safety.

Easy Way to Supply and Control Pressure

The FPVA AirBox is controlled from any RS232, USB, or Ethernet port. Designed for lab fluidic applications, it generates precision regulated, filtered air from -500mbar vacuum to 500mbar pressures. A single 24V digital outlet allows control of dosing solenoids as well, offering a single control solution for many applications.

7


Scaling Up: Multi-Tip Dispense Systems

In many cases where a single solution needs to be dosed repeatedly, a single solenoid can be used to deliver fluid through multiple nozzles, reducing size while also saving cost. However, care needs to be taken to assure all of the fluid channels downstream are equally proportioned. Even in the best cases this will still add to some tip to tip CV variation, but often this is an effective way to achieve high dispense throughput economically .

Higher precision multi channel dispensing requires separate solenoid control of each channel, but the individual channels need to be calibrated to each other. Without proper calibration, small differences in solenoid turn on/off performance can cause tip to tip CV errors approaching 5% in some cases. Fine tuning solenoid performance can be difficult with may PLC and IO cards software having control resolutions of 1ms, or more; the more robust way to calibrate is by tuning the individual solenoid “hit” and “hold” currents to match solenoid performance. Controlling hit/hold can also substantially improve switching repeatability and heat generation, further reducing error. There are products available today that make this relatively simple to do.

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

Combine Festo’s 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 allows dosing different

fluids and filling microplate wells in parallel. At the same

time, the ability to control each valve individually closes

the gap on tip-to-tip variability—maximizing dosing

precision.

VTOE-8 Multi- Channel Dispense Head

Higher throughput lab automation projects can involve making millions of dispenses per day, well beyond what can be done with a single dispense head. Automating these processes can lead to significant improvements in quality and productivity. One of the biggest benefits to pressure-based dispense systems is their scalability. For example, individual dispense heads combine easily, either by mounting them on a rail or retaining plate. By doing this, multi-channel dispense heads that handle different aliquot volumes, fluids, and pressures simultaneously can be created.

Mounting a multi channel head on a robot arm, or a cartesian gantry creates an easily scalable high throughput platform with minimal engineering time. This can be ideal for targeted sample prep or assay automation where there can be unique precision, throughput, or cost requirements.

Precision designed flow passages, quality

components, and calibrated dispense orifices

give the 8 tip VTOE excellent precision for simple

integration into a liquid handling system. Tip to tip

CV is generally under 2% in most applications.

8


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/labauto or e-mail: [email protected]

white paper: control under pressure. how to use pneumatic

Documents