A perfect pipette tip, please!
Pipette tips are precision articles whose production is complex and technically demanding. In addition to a high-performance, repeatable injection molding machine, high-precision molds, fast robotics with valid part inspection, and automated networking of all components are required to manufacture them with the highest quality and cost-effectiveness. A new, fully coordinated turnkey system combines the specific requirements.
By Wolfgang Zangerle , Head of Business Development at Netstal
Due to the pandemic-related surge in demand, pharmaceutical and medtech manufacturers and suppliers are increasingly considering their own production of pipette tips. However, they often lack the technical background to build these themselves. Pipette tips for in-vitro diagnostics and other laboratory analysis must meet high quality standards and tight production tolerances. Specifically, the defined design tolerances must be met exactly in order to absorb the defined amount of liquid and transfer it without carryover.
In today’s automated liquid handling systems, capacitive liquid sensing is the predominant technology, which requires electrically conductive pipette tips. The perfect pipette tip (Fig. 1) is the result of an optimized production flow in which material, mold and production technology work together seamlessly.
Components of the production system
Complete production cells according to cGMP offer one option. The production centers can be continuously qualified and deliver both quality, production reliability and high volumes. Netstal demonstrated a reference system at K 2022: the all-electric machine of the ELION series has a clamping force of 120 tons in the medical version and works with an injection mold from Männer. The pipettes produced are gently and quickly removed from the mold by means of an automation system from MA micro automation and 100 percent optically inspected and dispensed in trays.
The production cell delivers fully tested „100 μl pipettes“ from a 64-cavity mold in a very fast cycle time of 5.3 seconds. The production center requires only 25 m² of production area, which corresponds to a gross capacity of around 43,000 pipettes per hour, i.e. around 1720 pipettes per hour and square meter.
Requirements for the injection molding machine
The injection molding machine must fulfill specific tasks for pipette production. In material preparation, for example, an appropriate plasticization must be selected which does not contaminate the raw material, does not de-homogenize it or even degrades it impermissibly. If one of these factors is not controlled, the pipettes could fail in the automated diagnostic process, necessitate repetition or even lead to incorrect measurements.
Netstal has devised a proprietary RFC control for accurate production results, which keeps the process of injection into the mold stable to produce high dimensional consistency at the pipettes. Figure 2 shows the difference in shot weight consistency for production with and without RFC control.
Precise mold
In addition to the high precision of Männer’s mold, the hot runner with its 64 nozzles must also be perfectly controlled and balanced in order to achieve symmetrical filling of the cavities and thus identical pipettes. This is ensured, among other things, by temperature sensors at all 64 hot runner nozzle tips, whose signals are passed on to the G24 Gammaflux controller. The controller records the values 20 per second and makes adjustments if they deviate 0.014°C from the setpoint.
HB-Therm temperature control units are used for high-precision temperature control of the entire mold and, in particular, of all 64 cavities. Supply temperature, pressure and flow are controlled. 16 flow sensors monitor the 64 cavities and the return heating. The result is identical caloric conditions for all cavities. Any deviation must be avoided, as dimensional changes on the pipettes lead to rejects during the subsequent optical inspection.
Connected via OPC UA
To ensure that the various components and systems act correctly in the network, they are networked by means of OPC UA interfaces. The operator of the production unit can control all system units via a central panel and be guided by SMART OPERATION, the automated start and stop program from Netstal. The mold is also an important element of production safety. Using predefined sequences, the control system can guide the operator through their operating operations. This is important when producing in a four-shift system.
As soon as the pipette tips have cooled down to removal temperature and the mold moves up, the modular automation system from MA micro automation with its high-speed linear axis goes into action. It removes the 64 pipettes within 1.07 seconds and transfers them on. Now a quality shot can be removed or the parts continue to the camera inspection.
Inspection and clean room
Visual inspection is just one of many inspections developed by MA micro automation for fully automated production lines for the manufacture of pipette tips. The 100% inspection monitors wobble/curvature of each pipette. 100% inspection of the pipette tip (frontal and radial) and the pipette holder (frontal) can be additionally applied in a controlled manner to make absolutely sure that no pipettes are placed in racks that do not exactly meet the defined part accuracy. During the inspection, up to 48 measurements/second are performed, and this in a cGMP qualified state. After successful inspection, the pipettes are filled into appropriate racks, which are injection molded or thermoformed, or into bags, depending on the customer’s desired configuration.
Pipette production is subject to the requirements of a controlled environment, mostly cleanroom ISO 8 and GMP C. A qualification of the turnkey plant according to cGMP and the fulfillment of the corresponding clean room requirements is therefore mandatory, here the calibration of the machine plays a decisive role. Netstal is certified according to ISO 17025 and is also allowed to perform recalibrations on production equipment at the customer’s site to ensure the production consistency and validity of the machine.
First turnkey production
Until now, there has been no completely coordinated turnkey plant for pipette tips on the market. The novel production cell (Fig. 3) is an impressive result for hand-in-hand cooperation between the manufacturer and all suppliers involved. This makes it very easy for the customer to configure his own system. The time-consuming and cost-intensive trial-and-error phase is skipped; after successfully completed acceptance tests, the pipette cell is directly „ready to produce“ as a system. In addition to a high level of safety when taking the step into the product segment, the new production island offers maximum efficiency and the highest output in series production.
Highest precision and reproducibility under all conditions
The Netstal brand has always stood for high performance but also for maximum precision and reproducibility. The demands from the industry on the quality and consistency of the produced components are constantly increasing. The unique and highly accurate RFC injection control system from Netstal plays a decisive role precisely in this context. Thanks to stable mechanical construction, highly accurate measurement technology and sophisticated control technology, the injection units from Netstal achieve an extremely high shot weight consistency. This means that the user can fully rely on his production.
In addition to the high demands on precision and reproducibility, productivity is constantly increasing. Cycle times are decreasing and the number of cavities is increasing. An example of this is the production of pipette tips. Today, high-performance systems produce on 64-cavity molds with a cycle time of less than 5s.Netstal already proved at the K show 2016 that 128 cavities are also possible:https://www.youtube.com/watch?v=fZ19sM7-KQw&ab_channel=NetstalIn terms of quality and reproducibility, the control of the injection process plays a central role. Already when filling the cavities, it is decided whether the parts will be within the set tolerance or not.The developers at Netstal are aware of this fact and have always placed a strong focus on injection control. From the machine’s point of view, the control quality of the injection process is based on the following three features:
- Stable design and the most direct power transmission possible from the drive to the screw tip
- Highly sensitive sensors and high sampling rates
- Powerful control algorithms and real-time capable computer systems
Netstal RFC (responsive filling control)
The control of the injection process includes two phases:
- Injection phase
- Holding pressure phase
During the injection phase, the injection speed is tracked as the leading controlled variable. During this phase, the specified velocity profile is readjusted as accurately as possible and without delay. This can be seen clearly in the following screenshot in the diagram on the left.
Diagram: Injection phase (left) and holding pressure phase (right)
As soon as the cavities are filled volumetrically, the controller switches to the holding pressure phase and here the injection force is tracked as the leading controlled variable. This can be seen in the right diagram of the screenshot above.
The decisive factor is now how and at which screw position the switchover from speed to pressure control takes place. This is commonly referred to as v/P changeover.
Displacement or pressure dependent?
In practice, changeover is usually position-dependent. This means that the changeover takes place at a certain screw position, irrespective of the current quality of the melt. Due to various external influences, the melt quality can be subject to fluctuations, which are subsequently reflected in a greater scattering of the shot weight and thus of the component quality.
However, pressure-dependent changeover is particularly advantageous, especially for short injection times and fast cycles. Here, the changeover process is determined by the melt pressure. This strategy has the advantage that fluctuations in melt quality are automatically compensated. This leads to a higher shot weight consistency and thus to better quality reproducibility.
The pressure-based v/P switchover RFC detects very precisely when the mold cavities are filled volumetrically and the optimum time for initiating the holding pressure phase has been reached. This leads to a high shot weight consistency by automatically compensating for external environmental influences such as material fluctuations and the closing behavior of the non-return valve.
The role of the non-return valve
As a mechanical element at the screw tip, the non-return valve plays an important role in the injection process. Its correct function is a mandatory prerequisite for a controlled and cleanly controllable injection process. On the one hand, it must be ensured that the non-return valve seals well when closed and that no disturbing leakage losses occur, and on the other hand, the closing behavior is also of great importance. For these reasons, regular inspection and maintenance of the non-return valve is highly recommended.
To positively influence the closing behavior, the highly flexible functionality of the aXos control system can be used. Namely, if the metering process is designed in such a way that the back pressure is maintained at the end of the metering time, the non-return valve is actively closed after metering. The subsequent injection process can then already be started with the non-return valve closed, which further improves shot weight consistency. As of control version aXos 8.5.1, the user is additionally supported in this setting with a new synchronization mechanism, which significantly simplifies the setting process.
The result can be measured.
The precision and reproducibility can be demonstrated using the example of a test series on the „Connector“ component.
Diagram: Measurement series „Connector“
The diameter b was measured for 200 consecutive cycles. The mean value of the measurements was 18.499mm. The values scattered minimally by 0.008mm which, with the set tolerance of 18.5 +/- 0.0.1 mm, results in an excellent CpK value of 1.96 .
Quality through process reliability
Achieving high and, above all, consistent quality requires that the production process is 100% under control. The production system must be able to compensate for external influencing factors and ensure a sufficiently large process window with the available performance. Netstal machines provide the basic prerequisites for this right from the start: Stable construction, high-precision sensor technology and sophisticated control technology.
So when it comes to high-precision and reproducible production, it pays to choose Netstal.