Wednesday, 21 May 2014

Embedding 3D Printing in Research Labs

Taken by surprise by the Sheffield University 
alumni team at the Gibson virtual reality suite 
that they helped to fund!

Three 3D printing (3DP) is revolutionising manufacturing. It was during a visit to the University of Sheffield's Advanced Manufacturing Research Centre that Professor Keith Ridgway first made me aware of the power of the concept, which involves the systematic deposition of layers of material, in response to a digital design, to build an object. On the same visit, I was also introduced to the power of virtual reality in working with three dimensional objects from jet engines to protein molecules. A year later my colleagues and I raised funds to install a similar projection system into the Department of Molecular Biology and Biotechnology at Sheffield (top left). The room was subsequently opened by Nobel Laureate Ada Yonath, in honour of the Department's second Head (after Sir Hans Krebs), Professor Quentin Gibson, FRS (1918-2011). The ability to visualise the oxygen binding site of Haemoglobin and watch as the protein's iron centre, attached via a Porphyrin Ring responds in conformational terms provides students and staff with huge insight into Biomolecular interactions, something I am sure Quentin would have loved!

Quentin making, fixing,
but always thinking!
The powerful visualisation of objects in three dimensions is a great way to provide young scientists with a deeper appreciation of the molecular process that underpin life. However, I was recently persuaded by my physics graduate, George Rule, who helps me in the Innovation Labs here at the UTC,to obtain a 3D printer in order to generate molecular models to aid in the teaching of Molecular Biology. Printing DNA duplexes and scale models of bacteriophage particles proved a real success in explaining to the students (ranging from 14-19) the principles of molecular structure and function. However, I remembered my AMRC visit and the impression left, together with something Quentin told me when I visited him shortly before he died in New Hampshire, USA. When I sought his advice on making your way in Biochemistry he gave me the following answer. If you are trying to solve a problem and you are limited only by money for staff and resources, but not by intellect and determination, then you can still be innovative if you build an instrument that measures an important property of a molecule or cell, that nobody else can (that's Quentin top right,  still making things while in his early '90s!). In other words, one way to be a successful scientist, is to incorporate a level of design and manufacturing into your laboratory programme. This is where 3DP comes in.

Mini-racking system to hold 
Pasteur pipette columns
You may have read recently about the publication of a paper that describes the fabrication of a powerful microscope using paper, a small battery and a cheap lens by Professor Manu Prakash . In his work Prakash reminds us that scientific breakthroughs do not always rely on high end, specialised instrumentation (which incidentally usually come in at a high cost in terms of both purchase and maintenance). By embedding 3DP into a contemporary Molecular Biology laboratory, I believe a new generation of scientists will flourish using Quentin's guiding principle. Let me give you some examples of how we are following this concept at the UTC.

My own interest in teaching commercial aspects of Science (Molecules to Market courses) from GCSE to PhD, led me to assemble a group of Y12 students interested in the technical side of Science, to form Greenland Biodesign (an in-house organisation at the UTC, taking its name from the UTC's location on Greenland Street and the students' own idea, since Biotech was taken!).The students have interests ranging from general Biology, Biochemistry and Genetics through to Chemistry, Physics and computer aided design. In between formal classes, the Greenland Biodesign (Web site coming soon!) team are working on individual, basic and applied science projects, but are also driving the organisation of the large scale experiments (100 students) that we carry out weekly in the Innovation Labs. The first UTC project that combines custom manufacturing via 3DP is partly funded by the Royal Society and involves the development of the Mealworm  Beetle (Tenebrio molitor above right) as a "School Friendly" model organism. The aim is to develop Biochemical resources (Proteomics, Genomics and Transcriptomics) and methods for illustrating Biological phenomena from Developmental Biology to the molecular basis of enzyme catalysis.

The idea behind our
Greenland sonicator cup
Greenland ice breaker
Using our standard work flow planning approach (template on the RHS links, if interested) students are asked to work in small teams to develop robust extraction procedures for proteins, DNA and RNA. The first stage of the project is focused on larval biochemistry and utilises meal worms that are bred in house this is a separate programme run by Greenland Biodesign).We also use freeze dried meal worm in some situations (which can be obtained readily from a some supermarkets or on line for small change!). Mechanical extraction (homogenising and grinding) can generate undesirable heat and so we needed to keep the material cold prior to chromatography on our racking system (above left). We use glass homogenisers in some cases (for DNA and RNA), but sonication is something we are planning for protein extraction, since there are some oxygen sensitive proteins released. We have designed sonication cups based on ancient principles (top left!) for sample cooling during extraction  in order to circulate the extracts through ice, during sonication (our designs will all be made available shortly via the Greenland Biodesign web site). 

One of the major challenges that I have encountered in successfully delivering large scale lab projects with very young (14 year old) students (and indeed with some Graduates), is sample management. We use fridges and freezers for sample storage. We are often faced with storing up to 10 samples for 25 different project teams each week; these samples may be needed again during the course of a year. Whilst this is something a PhD student or commercial scientist must deal with every day, it is a skill that we believe needs teaching in a formal manner at the UTC. 

3D printed objects used
in Science education
The Greenland team have designed and fabricated a range of customise tube holders, capable of accommodating Eppendorf sizes to Falcon tubes, Universals, centrifuge tubes etc with mix and match options for different experiments. We have also developed an expandable racking system for the long term storage (and easy access) of samples  at -80. The recent design of a round rack for multiple tube sizes (Greenland Icebreaker, above right), that is free standing without a base, has proved really useful when the sample need to be embedded in ice. 

We are fortunate that we have equipped the lab with simple, but versatile bench top items
Greenland gel formers
such as micro centrifuges (for both simple deposition of microlitre volumes and extract separation), which satisfy lab needs, but we are reaching capacity with electrophoresis equipment and our mini-agarose gel templates and combs (right) are the first step in expanding our DNA separation and analysis capabilities. And all for under a quid per gel former! However, plastic gel equipment in high use by young scientists in waiting, can take some "hammer" and we use 3DP to fix parts, and to replace those components like gel spacers and combs that seem to disappear with the same frequency as socks in a washing machine!

Greenland freezer racks
These are just a few simple examples of how a 3DP facility embedded in a research teaching lab (which forms a key element of our approach to teaching practical laboratory skills and investigative science at the UTC). However, I believe that every University department (or indeed a research group of around 10 students and post-docs) should consider integrating 3DP into their daily lab infrastructure and routine. It is Quentin Gibson's advice that I can hear in my head when I think of the challenges associated with producing competitive Life Science Research (particularly Molecular Biology and Biochemistry) which must be overcome in order to obtain the necessary research funding. By combining creative thinking, robust technical and analytical skills with 3DP, I believe there could be a renaissance in experimental science and I believe the young scientists at the UTC are in the vanguard of this renaissance.

1 comment:

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