Liquid handling robot
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Nov 01, ; Accepted Date: Jan 03, ; Published Date: Adv Robot Autom liquid handling robot system This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original liquid handling robot system and source are credited. We describe a unique liquid handling platform, based on a Tecan EVO, specifically designed for the preparation of analytic calibrators and quality control samples according to the requirements of the Good Laboratory Practice GLP.
The platform utilizes a combination of off-the-shelf software Tecan Gemini 4. The system convinces with robust and reproducibly quality and a very easy, intuitive user interface. The regulations of GLP demand the independent preparation of calibrators and QCs, which, being measured simultaneously, shall match each other within strictly defined criteria [ 12 ]. These preparations may need to be repeated, if the study runs over longer time, or an unexpected number of repetitions lead to further demand of standard and QC material.
A manual approach is time and labor intensive. Moreover, mismatches between calibrators and QCs tend to happen, with consequently repeated preparations. This leads to a higher consumption of valuable reference substance used, such as stock material and blank matrix e.
A robotic approach in contrast could guarantee constant and robust day-by-day or bulk preparations of calibrators and QCs and may help to overcome waste of material and time.
This paper describes a unique liquid handling platform allowing for an easy, robust and reproducible fully automated production of calibrators and QCs, utilizing a custommade software application being liquid handling robot system full compliance with 21 CFR part 11 [ 3 ].
The robotic platform consists of a cm Tecan Freedom EVO equipped with an 8-channel liquid handling arm LiHaa barcode scanner PosIDtwo on deck shakers and diverse carriers for tubes and troughs Tecan. The software package runs on Windows 7 and can be installed on multiple PCs to allow for separation in a development and production environment.
A full computerized system validation was applied [ 45 ] before setting the system into productive usage. Apart from the deck layout with all aspiration and dispense vectors, the Gemini administers liquid class settings, such as aspiration and dispense height and speed for any solvent used in the different bioanalytical methods e. Eight carriers are reserved for barcode-driven aliquoting of the prepared liquids into small cryotubes for later usage in the laboratory.
The system checks before dispensing the aliquots, whether the destination tubes have the correct barcodes for the respective solution. This avoids accidental mixing of incorrectly labeled tubes into one series and later unpleasant surprises when e.
The deck constantly contains several tip carriers, dedicated racks for source and destination tubes e. Up to six different solutions can be added to the reagent troughs. Display of all bioanalytical methods 2. Display of sets link between pipetting scheme and deck layout 4. Control panel for executing a method 5. Run window with status of processed steps of worklist 6. Liquid handling robot system panel for barcode check, worklist generation, and aliquoting 7.
Table presenting the pipetting scheme, including source and destination IDs, concentrations, volumes and liquid class. Required volumes automatically get calculated by concentrations and final volume 8. Labware display for rapid check of tube or trough locations. For multi-analyte methods, the SPIKE can handle the preparation of working solutions containing multiple stock solutions, liquid handling robot system the diluent volume being correctly calculated Figure 3.
WS1 STD is prepared from three different stock solutions Stock 1, 2, 3 with different original concentrations, but requiring the same final concentration in the mixture. By saving the method, the table and set will get accessible liquid handling robot system the end liquid handling robot system to execute the method and prepare the desired solvents in the defined volumes.
Since calculations are embedded into the SPIKE, the end user can scale the final volume up and down on demand, while the software will automatically adjust liquid handling robot system required volumes of stock solution and diluent. Moreover, the SPIKE recognizes, whether the volume to be transferred requires high or low volume tips and will adjust the aspirated volume per pipetting channel accordingly. If solutions are prepared on the embedded mixers, mixing mode speed, direction etc can be defined within the set.
If no shaker is chosen as destination location e. By creating a worklist, all steps or only parts of the table can be chosen for execution. When the worklist is prepared and visible in the run window, the method can be executed.
After execution, a pdf report is generated listing the accomplished steps and volumes together with the login information user, date and time. The spike has several control functionalities for testing a method working as expected. SPIKE would not allow running an application with e. It requests the user to weigh the empty tube and will interrupt the preparation of the solution after each step to allow the user to weigh the transferred liquid volumes.
By comprehension of the specific weight of the solvents, the SPIKE liquid handling robot system calculate whether the transferred volumes are correct, or whether adjustments are necessary liquid handling robot system the affected liquid class. Regarding data security, access levels and user rights define which user can create or modify a liquid handling robot system within SPIKE and Gemini, and who is limited to executing methods. For biosimilars as liquid handling robot system emerging market, it is recommended to assess independently prepared standard curves, derived from stock material from the liquid handling robot system drug and the biosimilar drug.
The idea is to avoid variabilities from the preparation as much as possible, in order to keep the reference substances the only relevant variable. For a biosimilar ELISA method, we used our robotic approach and prepared these standard curves, via several dilution steps, and sorted them in alternating order on the assay plate as recommended by Marini et al [ 6 ].
The standard curves yielded from these independent robotic preparations liquid handling robot system found to be well in accordance to each other, not only within the preparations from one reference substance but also when curves were compared between originator and biosimilar Figure 4.
Overlay of six standard curves separately prepared by the described robotic system. The liquid handling robot system system and software described here has been proven to be a valuable tool for improving robustness and reproducibility of calibrator and quality control sample preparation.
By introducing this unique platform in cooperation with Fornax Technologies GmbH und Co KG, Celerion Switzerland is the first Contract Research Organization to utilize robotic liquid handling systems not only for sample processing, but also for the time and material sensitive steps during the lead-in of preclinical or clinical studies.
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