Ultimate precision
New fully-automatic coating system for diagnostic products

Diagnostic products in combination with biopharmaceutical drugs are taking on a new significance. A new fully-automatic coating system is now available which is designed to handle the complex workflows.
Accurate, reliable diagnosis of infection and disease is becoming increasingly important, especially where biopharmaceutical products are involved. Optima has taken an entirely new approach to automation of micro-titration plate production for diagnostics applications. The project is based on micro-titration plates with 96 wells. During the very high precision coating process, substances are placed into the 96 wells from two to four times in multiple process/intermediate steps depending on the product. The system offers different incubation times and includes extraction, drying and control stations. It deposits high-precision multi-layer coatings around the edges of micro-titration plates, and it can dose around 24 different diagnostic substances.

The U-shaped system is divided into three process segments. A fourth segment, the incubation zone where the micro-titration plates are held in magazines during the incubation time, is located inside the U. The three process segments are linked together. The incubation phase can be included between two process sequences or the plates can be routed via a bypass to the next process segment. To maximize system utilization, multiple batches can be processed simultaneously.

Single-position time-pressure system

A loading station with a capacity of around 200 plates is located in the first process segment. The height of the micro-titration plates is checked prior to coating. If the height exceeds the defined limit, the plates are immediately removed. The plates are deionized and the orientation is checked. If the plates are the wrong way around, they can then be rotated 180°. A printer applies a unique batch and plate number to each plate and a data matrix reader verifies the printing.

The filling station is a single-position time-pressure module with temperature compensation. In this configuration of the filling system with 96 needles, dosing accuracy must be kept within very tight tolerances to comply with the diagnostic product manufacturer’s specification. An extremely uniform distribution in the manifold was needed to achieve this level of performance.

During in-process control, the micro-titration plates with filled wells are lifted off the conveyor with the aid of a linear motor and pressed against a stop with a defined force. Eight optical sensors move in parallel over the rows which have twelve wells each. Each sensor detects and records the fill level (height) which is then used to calculate the fill volume. The maximum allowable tolerance is 0.1 mm. If one of the wells fails to meet this criterion, the entire micro-titration plate is rejected.

Non-conforming plates are removed and placed in an overhead reject station. The reject station has a capacity to temporarily store ten micro-titration plates, allowing the machine to continue without interruption.

Space for 21,000 micro-titration plates

Under the command of the system controller, the plates are moved to the second process segment via a 90° bypass (pneumatic axis) or placed in a magazine for incubation. If the micro-titration plate is moved from the process segment to the incubation zone, a robot is activated which grasps the magazines by a ball head at the top and stabilizes them at the bottom as it positions them vertically into the designated pallet slot. The incubation zone has twelve pallet slots which can hold up to 35 magazines each, providing space for 21,000 micro-titration plates.

Management of the incubation zone is provided by the robot’s dedicated computer-based controller which “collaborates” with the three process segments. Micro-titration plate data, storage time and storage slot management are handled autonomously and automatically.

The robot loads and unloads the magazines within 15 seconds on average. The micro-titration plates are retained in the incubation zone for periods ranging between ten minutes and 36 hours depending on the diagnostic fluid. It takes that much time for the liquids to work into the area around the edges to create a defined coating in combination with the downstream processing steps. The incubation times are stored in the storage station controller. The robot then returns the micro-titration plates to the process.

Using FIFO (first-in-first-out) sequencing, the micro-titration plates are moved to the second process segment with the aid of a destacker and a temporary storage station. Other micro-titration plates can be moved directly to the second process segment via the bypass depending on the commands issued by the system controller for the particular product. Four extraction stations and four time-pressure stations are located in the second process segment. The configuration of the dosing systems is exactly the same as in the first process segment.

The plates are moved to the third process segment either directly or following an additional incubation period, and processing begins with the familiar destacking operation. The micro-titration plates pass through three extraction stations, three time-pressure filling stations and 100% in-process control. They are then routed to additional drying stations and another extraction station. The drying aspirator has larger needles which are needed to dry the wells. At the end of this process, no more than 0.03 µl of liquid remains in each well.

When the coating process is finished, the micro-titration plates are transferred to the unloading station. The plates are piled into stacks of ten to 25 units, and they are then placed onto two parallel conveyors without interrupting the flow. An operator removes the stacks from the conveyor.

Pioneering achievement in record time

The system is highly complex, was designed almost totally from the ground up, and is highly efficient. Process stability plays a key role in production efficiency, and redundancy is another important factor. The robotic system in the incubation zone, for example, is made up of two units. The ability to process multiple batches in parallel is a major reason why this coating line delivers such high ROI. Automatic control systems to handle parallel production were developed in collaboration with Seidenader Automation, which also provided the complete SCADA system.

Trials with other technology were conducted before the decision was made to deploy optical sensors for in-process control. The single-position time-pressure system with 96 needles also represented a significant challenge. To ensure uniform filling and adherence to very tight tolerances, the flow distribution to 96 needles had to be calculated and optimized.

Conclusion

This type of project demands extreme commitment by everyone involved including the customer who takes part in the coordination process and deployment. Time pressure was intense from day one, as is reflected in the aggressive project schedule. The contract was awarded in October 2006, and acceptance took place in November 2008. Installation was carried out between January and April 2009. The customer appears to be highly satisfied with the final result and has placed a follow-on order for a system which is currently being assembled.