Towards robotic laboratory automation Plug & play: Survey and concept proposal on teaching-free robot integration with the lapp digital twin.

The Laboratory Automation Plug & Play (LAPP) framework is an over-arching reference architecture concept for the integration of robots in life science laboratories. The plug & play nature lies in the fact that manual configuration is not required, including the teaching of the robots. In this paper a digital twin (DT) based concept is proposed that outlines the types of information that must be provided for each relevant component of the system. In particular, for the devices interfacing with the robot, the robot positions must be defined beforehand in a device-attached coordinate system (CS) by the vendor. This CS must be detectable by the vision system of the robot by means of optical markers placed on the front side of the device. With that, the robot is capable of tending the machine by performing the pick-and-place type transportation of standard sample carriers. This basic use case is the primary scope of the LAPP-DT framework. The hardware scope is limited to simple benchtop and mobile manipulators with parallel grippers at this stage. This paper first provides an overview of relevant literature and state-of-the-art solutions, after which it outlines the framework on the conceptual level, followed by the specification of the relevant DT parameters for the robot, for the devices and for the facility. Finally, appropriate technologies and strategies are identified for the implementation.

Towards robotic laboratory automation Plug & Play: The "LAPP" framework.

Increasing the level of automation in pharmaceutical laboratories and production facilities plays a crucial role in delivering medicine to patients. However, the particular requirements of this field make it challenging to adapt cutting-edge technologies present in other industries. This article provides an overview of relevant approaches and how they can be utilized in the pharmaceutical industry, especially in development laboratories. Recent advancements include the application of flexible mobile manipulators capable of handling complex tasks. However, integrating devices from many different vendors into an end-to-end automation system is complicated due to the diversity of interfaces. Therefore, various approaches for standardization are considered in this article, and a concept is proposed for taking them a step further. This concept enables a mobile manipulator with a vision system to "learn" the pose of each device and - utilizing a barcode - fetch interface information from a universal cloud database. This information includes control and communication protocol definitions and a representation of robot actions needed to operate the device. In order to define the movements in relation to the device, devices have to feature - besides the barcode - a fiducial marker as standard. The concept will be elaborated following appropriate research activities in follow-up papers.

Detection of Biologically Relevant Low-Titer Neutralizing Antibodies Against Adeno-Associated Virus Require Sensitive In Vitro Assays.

Patients with preexisting anti-adeno-associated virus serotype 8 (AAV8) neutralizing antibodies (NAbs) are currently excluded from AAV8 gene therapy trials. Therefore, the assessment of biologically relevant AAV8-NAb titers is critical for product development in gene therapy. However, standardized assays have not been routinely used to determine anti-AAV8-NAb titers, contributing to a wide range of reported anti-AAV8 prevalence rates. Using a clinical in vitro NAb assay in a separate study, a higher than expected anti-AAV8-NAb prevalence of about 50% was found in international cohorts. This comparative study has a translational character, confirming the biological relevance of anti-AAV8-antibody titers measured by this assay. The significance of low-titer anti-AAV8 NAbs is shown, along with the relevance of the in vitro assay cutoff (1:5) compared with other assays. Importantly, internally standardized reagents and purified AAV8 constructs containing 90% full capsids were used to reduce the effect of empty capsids. It was found that even very low anti-AAV8-NAb titers (<1:5) could efficiently hinder transduction in vivo, demonstrating the importance of sensitive NAb assays for clinical applications. The in vitro NAb assay was found to be more sensitive than an in vivo NAb assay and thus more suitable for patient screening. Additionally, the study showed that anti-AAV8-NAb titers <1:5 were very rare, further supporting the in vitro assay. However, assays using a lower cutoff may still be useful to explain potential variances in transgene expression. These findings support the relevance of the higher than expected prevalence of anti-AAV8 NAbs, highlighting the need for strategies to circumvent preexisting anti-AAV8 NAbs.