Bioreactor Design Tips

Bioreactor design, whether for research automation or scaling up of production, is a very common task for the Tissue Engineer today.  As an interdisciplinary field it is common to find people very skilled in one area, but lacking in another.  This article will shed light on a few things a mechanical engineer might think about when considering Tissue Engineering bioreactor design.

  1. Disassembly:

    The golden rule is that everything should be easily disassembled and sterilised.  Do not glue parts together or fix them in a way that means there is (even potentially) an area which cannot be cleaned in the join.  Preferentially, mill parts from solid blocks or mould them in one part so that they do not need to be constructed from joined subcomponents.
  2. Simplicity of Assembly:

    Don’t forget that your user will need to set up the system within a sterile environment, which often means a class II or higher tissue culture hood.  The user will be wearing rubber gloves and working at arms length whilst following the many restrictions of sterile procedure.  A good rule of thumb here is to design something that you could put together with one hand whilst sat on a chair arms-length away from the table you are assembling on.
  3. Zones of sterility:

    Any material which contacts the culture medium or the cells must be both sterile and biocompatible.  It must not influence the culture or the cells by ions it releases.  A good option here is the use of a silicone or a perspex/acrylic part.  These can be sterilised with alcohol but do not last that many sterilisation cycles.  For short term use systems, stainless steel of grade 316 or 316L is possible; however these still release ions and cause problems for the cells in the longer term.  Any other non-contacting surfaces just need to be sterile – which means that stainless steel is a good choice, as is aluminimum where weight is a concern.  Make sure that the metal parts can be removed and autoclaved, and the plastic parts can be alcohol sterilised.
  4. Operating conditions:

    Cells require definiate culture conditions, and these are usually provided in a laboratory through the use of a cell culture incubator in conjunction with a buffered medium that maintains the right pH.  This is a very good system, and you need a very good reason not to make use of it.  Preferentially, design your bioreactor to fit within a cell culture incubator – so that it can take advantage of the carbon di-oxide and temperature control.  To use a buffered cell culture medium you need to permit gaseous exchange between the medium and the atmosphere within the incubator so that the enhanced carbon dioxide level can be used for buffering – this must be a filtered gaseous exchange as the internal atmosphere of the incubator is not entirely sterile.
  5. Heat and Humidity:

    An incubator or other cell culture environment will run at almost 100% humidity and operates at 37 degrees, conditions which mean careful device design.  In particular, electric motors will frequently overheat during use; or at the least, the heat they produce will overpower the temperture control.  A water cooling system is a good solution – this can be pumped or gravity fed (for short term experiments) from a reservoir outside the incububator, such that cool fluid runs through fine pipes over the surface of motors or other components which get hot.  Another very effective means of avoiding overheating and the negative effects of high humidity on electronics is to move them outside the incubator and make use of power transmission.  A wire-pull system will reliably move linear motion into a system, as will pneumatic or hydraulic drive devices.  These may have the added advantage of easier moving of the system from the tissue culture hood where it is assembled to the incubator where it will operate.

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