Donald S. McNeil and Dan Bantz

Laboratory instrument design engineers know that the secret to device precision lies in the subsystems. If you can improve the performance of the subsystem componentry, total system performance also improves. At the same time, the need to improve the subsystem components must be balanced against the need to quickly perform the tasks at hand, thereby increasing throughput and reducing the cost per sample. Often, technology limitations—including in the area of liquid handling—lead to tradeoffs between these needs, rendering decision making difficult when new instruments are designed.

An instrument’s sampling and reagent subsystems typically have the greatest potential to influence performance results. When such subsystems introduce a sample into a lab instrument, it must deliver a precise quantity to the reaction vessel to avoid impacting subsequent instrument operations. The same holds true for the reagent-addition system. If too much reagent is delivered, downstream errors are typically multiplied. While instrument manufacturers in many cases can compensate for accuracy issues, compensating for precision issues is very difficult. The fluid-delivery systems used in lab instruments must ensure this precision.

Trials and Tribulations of Low-Volume Dispensing

Newer generations of laboratory instrumentation are designed to reduce the liquid volumes used in sampling and reagent additions. This reduction increases throughput, promotes the efficient use of precious sample, and lowers the consumption of expensive reagents. It also reduces liquid waste, which helps to offset increasing waste disposal costs. Furthermore, the use of smaller liquid volumes enables labs to employ more-efficient chemistries and fluid dynamics, improving instrument throughput.

Among the most common pumps used for aspirating and dispensing liquids are syringe and piston pumps—positive-displacement technologies that provide the best accuracy and precision in liquid-flow applications. In contrast, air-displacement pumps are less precise than positive-displacement pumps and typically require disposable tips. Moreover, they add to the cost per sample and generate solid-waste disposal issues.

Existing pump technologies—including both positive- and air-displacement types—are least effective when they are used to dispense low microliter or nanoliter volumes of liquids. At such low volumes, fluid dynamics can prevent a portion of the dispensed liquid from reaching the target vessel because a portion of the liquid tends to remain on the end of the probe, compromising accuracy and precision.

While syringe and piston pumps are well suited for aspiration and dispensing operations when delivering larger volumes of liquid, they generally struggle when handling liquid volumes at levels around 10 µL and lower. At such low volumes, most such pump systems lack the resolution and speed to deliver liquids accurately and precisely and cannot prevent droplets from remaining on the probe, resulting in imprecise performance.

Most syringe and piston pumps use stepper motors to drive the syringe plunger or piston. While this technology has served the industry well for several decades, it is limited in its ability to deliver very small volumes of liquid at high throughput rates to accelerate data collection. In addition, stepper motors offer limited resolution, which is measured in the number of steps in which the syringe or plunger length can be divided—3000 in the case of most stepper motors. Although microstepping can be employed to increase this resolution to between 20,000 and 30,000 steps full stroke, it can do so only at the expense of accuracy and speed.

The ability of standard syringe and piston pumps to handle tiny quantities of liquid can be improved by using small-volume syringe barrels or pistons. Unfortunately, these solutions cause priming issues because bubbles tend to adhere to the small passageways inside the syringe or piston assembly. In addition, stepper motor–driven syringe and piston pumps have difficulty in handling small volumes of liquid because these volumes have lower velocities. They therefore do not create sufficient acceleration, running speed, and deceleration to overcome the surface tension that retains the droplet in the probe. As a result, system reproducibility is compromised because the lack of precision in the sampling and reagent system translates directly into test result errors.

The issues associated with customary syringe and piston pumps can be solved by using larger-volume syringe barrels or pistons. Assuming that the motor’s acceleration, running speed, and deceleration are rapid enough to clear the droplet from the probe precisely, barrels and pistons should be able to handle at least 500-µL volumes to increase fluid velocity, although 1000 µL volumes are preferred. However, stepper motors do not achieve sufficient acceleration, running speed, and deceleration to reliably eject the droplet. Moreover, larger-volume syringe or pump heads, coupled with the resolution limitations of typical syringe pumps, reduce the ability of such pumps to accurately and precisely deliver the correct amount of liquid at low dispense volumes.

Because of their size, most syringe and piston pumps are mounted deep within the dispensing instrument and use long transfer lines to transport fluid to the probe. Because these lines typically average about a meter in length, they reduce the pump’s fluid-metering performance, increase liquid waste, and decrease throughput.

Improving Pump Performance

Laboratory instrument manufacturers have indicated that the ability to perform reliable low-volume, noncontact dispensing, along with aspiration, is a pressing need. Hence, this need was considered during the design of a new syringe pump. The manufacturers also asked that a new pump be smaller and lighter than previous models and that it be able to accommodate standard 30-mm syringe barrels. A smaller pump, they said, could be mounted on a motion system at the point of dispense, while the probe could be mounted directly on the pump, eliminating the need for a transfer line.

To perform low-volume, noncontact dispensing reliably, a pump must contain a motor that can achieve much higher acceleration and speed than current stepper motors can. And to provide the resolution needed for dispensing microliter volumes of liquid using a large-volume syringe barrel, the motor must be capable of many times more steps than the 3000 typically provided by standard syringe pump stepper motors or even the 20,000 to 30,000 steps provided by microstepping motors. These capabilities are provided by a newly designed syringe pump driven by a position-control servomotor. The pump provides the flow velocity required for ejecting the droplet from the probe while providing the resolution required to precisely and accurately deliver the right amount of fluid at high throughput using a larger syringe barrel.

To test the capability of different pump technologies, we compared the performance of the newly designed syringe pump and the most precise and accurate 30-mm (half-height) syringe pumps from three leading manufacturers. Each of the pumps was optimized to provide the best low-volume, noncontact dispense performance. While one of the pumps required a special barrel plunger thread, all the others used the same 1000-µL syringe barrel. For all of the pumps, the same swaged-design probe was used to improve the droplet-cutoff characteristics.

To provide the best noncontact, open-tube dispense performance, all of the pumps were tested at their maximum acceleration, running speed, and deceleration. In addition, they were tested at the maximum resolution possible to provide the best accuracy and precision performance, balanced against the available motor torque. Because of motor-torque limitations, the stepper motor–driven pumps tended to stall at high-resolution setpoints and high speeds. The data in Table I show the performance of the newly designed syringe pump—with a transfer line or with a mounted probe—and the performance of the conventional syringe pumps.

When all the pumps were connected using a 1-m transfer line, the new syringe pump design dispensed fluid more precisely than the other pumps, as presented in the table. Performance improved further when the probe was attached directly to the pump, thereby eliminating the use of the transfer line. Using the transfer line, none of the pumps could dispense 1.5-µL droplets in noncontact operation, but when the probe was mounted directly on the new syringe pump, it could deliver this volume with good precision.

Conclusion

The servomotor-driven syringe pump’s improved resolution, fluid velocity, acceleration, and deceleration characteristics enable laboratory instrument manufacturers to quickly and reliably perform noncontact dispensing of small volumes of liquid. Its small size and weight also allow engineers to eliminate the transfer line and shrink the size of lab instruments, making them more attractive to end-users in today’s lab environments, in which space is at a premium.

Donald S. McNeil is senior product manager at Parker Hannifin Corp., Precision Fluidics Div. Reach him at [email protected].

Dan Bantz is senior applications engineer at Parker Hannifin Corp., Precision Fluidics Division. Reach him at [email protected].