Deciphering the Burgess Shale of single-use bioreactors

By Mark Selker and Barb Paldus

One of the most famous of the Beatitudes, “The meek shall inherit the earth” (Matthew 5:5), has been likened by Darwinists to the ascendance of little furry mammals after a meteorite hit the Earth, initiated the Ice Age, and damned the almighty dinosaurs.

“How will the 'survival of the fittest' principle apply to designs and vendors of single-use equipment?”

In the bioprocessing industry, single-use enthusiasts would claim that the dinosaurs are really large-scale stainless steel infrastructure, the furry mammals are disposables, the housing market/stock exchange collapse in 2009 is the meteorite, and the current recession is the Ice Age. Market drivers – the natural selection criteria in this case – such as lower capital, skilled operator labour and validation costs, biosimilars price erosion and time to market, are accelerating the adoption of the single-use paradigm.

An interesting question, drawn from evolutionary biology, therefore emerges:
How will the ‘survival of the fittest’ principle apply to designs and vendors of single-use equipment?

The recent proliferation of mid- to large-scale (25L to 2,000L) single-use bioreactor designs has focused primarily on aeration and agitation methods. Agitator types include single to multi-impeller configurations with different blade geometries (Thermo Scientific and Sartorius-Stedim), magnetic motors (XCellerex), paddles (ATMI), rotating wheels (PBS Biosystems) and even two- (GE Healthcare/Wave) and three-dimensional (Cellution BioSystems) rockers.

Aeration methods range from traditional frit and open pipe spargers (Thermo, Sartorius, and XCellerex) to air-lift designs for more efficient oxygen transfer with lower shear stress (XCellegene and PBS). Bioreactor geometries either mimic typical cylindrical stainless steel vessels, or present a radical departure, with shapes such as rectangular prisms (ATMI), pillow bags (Wave), cones (XCellgene) or U’s (PBS). In the lab-scale arena (0.5 L to 50L) new disposable vessel designs are also becoming more and more numerous (e.g.: Millipore’s Mobius, New Brunswick’s CelliGen, and Artellis’ iCELLis).

In essence, single-use upstream bioprocessing equipment is experiencing the equivalent of the Cambrian explosion, with many diverse species trying to survive and thrive. As Stephen J. Gould so aptly described in his book A Wonderful Life: The Burgess Shale and Nature of History (1989), the “history of life is a story of massive removal followed by differentiation within a few surviving stocks”.

A common need, however, has clearly emerged for single-use sensors and easy-to-use process automation, and efficient validation of both. There are many operations, even in single-use bioprocesses, that can be improved to reduce burden and time load to ensure end-user success. As many of the vendors have focused exclusively on disposable bags and bioreactors, if one vendor can indeed provide an intelligent, self-calibrated measurement and automated solution, it will carve out a unique and lucrative niche.

This provider could symbiotically exist with all bioreactor manufacturers, providing a unique service to the entire bioprocessing industry. To extend the evolutionary biology analogy, this vendor would resemble homo sapiens, both from the ability to problem-solve, but also to use, and eventually even create tools.

If we follow Gould’s train of thought, such a creature with intelligence and self-awareness would surely have evolved. However, Gould himself concluded that evolution was “not the conventional tale of steadily increasing excellence, complexity and diversity”. He based this argument on the fossil fauna records from 530 million years ago that are found in the Burgess Shale. He argued that chance played a central role in the selection or the survivors, and that given the chance to “rewind the universe”, the outcome could have been altogether different, even for the homo sapiens species. In other words, our planet could just as well be ruled today by intelligent gecko lizards, using genetically modified canaries in their drug development trials.

If we return to the original question: which companies will win the ‘survival of the fittest’ game to become the dominant players in single-use bioprocessing? What will happen to XCellerex, Artellis, PBS Biosytems, Sartorius and Finesse? Only the future fossil record will tell, and for now, the Universe is mum, but continues to roll the dice.

Biography

Mark Selker has worked and published in various areas within the optics industry.  He has worked for NASA, Coherent Laser Group and Harmonic, and most recently has been a visiting scholar at Stanford University. Selker received his ScB and Ph.D in electrical engineering from Brown University in 1986 and 1990 respectively.
 
Barb Paldus was most recently the CTO of Picarro, a company she founded in 1998. Her efforts there culminated in solid-state Cyan laser products in 2003 and cavity ring-down spectroscopy products in 2004. Barb received both her PhD (1998) and MSEE (1994) degrees in electrical engineering from Stanford University.