Did you know that InSphero was the first biotech company to successfully ship live 3D spheroid models to labs worldwide in an assay-ready format? And we are still one of only a handful of companies able to do this. Shipping these delicate living microtissues, while preserving their physiological function so that they are ready for compound dosing within hours upon receipt, is not a trivial task. That’s why we have continued to improve and refine different elements of our shipping technology over the past decade.
In this blog post, I want to share with you how we deliver assay-ready microtissue models to our pharma and biotech partners internationally and what obstacles we had to overcome to make this a robust and accessible technology available for all.
InSphero 3D InSight™ assay-ready microtissues are complex, multicellular constructs assembled and matured using elaborate, highly standardized procedures to the point they leave our production facilities for their journey to our partners' labs. We ship these live, ready-to-use microtissues in scalable, automation-compatible, and technician-friendly Akura™ plate formats that are engineered to make routine 3D-cell culture maintenance and assay tasks easier and more efficient.
The process of packaging and shipping these live mini organs from Switzerland to destinations in Europe, Asia, and North America poses unique challenges not only in terms of operational logistics, but also in the way these delicate products must be protected during transport.
Microtissues are free-floating entities, cultured and transported in multi-well plates engineered with special features that allow for better visualization, maintenance, and analysis of microtissues. For transport, the plates are sealed with a thermally glued membrane, creating an closed compartment for each microtissue.
Single microtissues in cell culture medium are located at the bottom of each well, where a cell-repellant surface prevents them from attaching to the plate. During shipment, the sealing foil secures the medium and microtissues in the wells, but if the plates are tilted more than 90° for longer than a few minutes, the microtissues will eventually roll to the top of the wells, where they can get trapped and damaged.
We therefore started to develop a new packaging system to ensure plates always remained upright during transport. The idea behind our novel design was inspired by clever techniques devised by our ancestors, who added keels and counterweights to their dugout canoes to prevent capsizing. Drawing from the same basic boat-building methods, we designed an inner sphere-shaped box holding the microtiter plates, inside an outer box with a spherical void shape accommodating the sphere. Between the two parts, a layer of regular tap water allows the sphere to float and thereby move freely. The weight distribution of the inner packaging is designed so that regardless of the position of the outer box, the plates inside the floating sphere always remain upright – keeping the microtissues at the bottom of the well during the long journey from our production facility to your benchtop — ready to assay after a media exchange and brief recovery period in an incubator.
Keeping the plates upright is one part of the shipping challenge we had to overcome – preserving structure and functionality of the complex mini-organs during multi-day transit times is another. Culturing microtissues typically requires high humidity, high CO2 levels and robust thermal management. In a lab setting, this is achieved through sophisticated cell-culture incubators. Providing a similar environment in a transport system is possible, as such highly specialized shipping systems exist, but they are typically heavy, expensive, and often cannot be transported by regular express parcel services.
We opted to go into another direction aiming to make our products more easily accessible and affordable to everyone keen on working with our 3D InSight™ technology. To preserve microtissue health and function during transport, we decided to design the packaging system for shipping plates and media so as to avoid harmful extreme conditions, such as low temperatures or pH fluctuations in the media, but without overly complicating the transport system. To minimize such extremes during shipment, we used lightweight materials with high thermal insulation coefficients, combined with thermoelements made with on phase-change materials.
These packaging elements, combined with transport media optimized for specific microtissues types, have proven to reliably safeguard the morphology and functionality of our live microtissues while in transit. Our spheroidal mini organs proved to be astonishingly robust entities. We did extensive testing on these microtissue models and observed excellent stability of the spheroids for transit times up to 96 hours, exemplified here by morphology, viability and functionality data of transport-simulated human liver microtissue cultures.
The tissues endure shipping conditions during at least 96h without any measurable loss in viability or functionality. This time window allows us to safely transport our products to every laboratory in our primary markets in Europe, Japan and the US. Typically, transit times to these destinations are substantially shorter than 96h, resulting in a comfortable safety margin in case of hold-ups in transit.
Being able to deliver truly assay-ready products in high quality internationally is key to make our complex 3D models available to a broad user base. We believe that putting this technology in the hands of as many researchers as possible, worldwide, ultimately contributes to discover better and safer drugs.
I hope you've found this blog useful. If you'd like to learn more, I encourage you to read Keren Sookne's article in Healthcare Packaging, in which InSphero Head of Technology and Platforms Olivier Frey discusses the challenges of engineering a shipping system to keep fragile live tissues always upright — and how our design team took their inspiration from boat design. To see for yourself how it works, watch this video of Olivier showing how to unpack the InFloat™ shipping system upon arrival.