But how does one downscale a washing machine, a starch factory, a bakery, or a textile mill to laboratory scale?
Doing this has been a key to Novozymes success. Today we have a range of tests, which reflects critical process conditions at our customers. We have strong in-house expertise in transforming the full-scale application to a size, which is manageable and convenient in laboratory, secures high through put, and has low sample demand.
All of these tests correlate to the final application, but in general the correlation gets poorer as the test is downscaled further. Therefore we often need a cascade of tests. Each step has better correlation, higher complexity, resembles real life application more and increases the likelihood that a given enzyme has good technical performance and thus can obtain commercial success.
Novozymes will further develop this ability in the future to ensure that our enzymes are world class in technical performance and live up to ? or exceed ? our customer?s expectations.
Correlation between application assays and reality
Novozymes earns its growth to development of new enzymes for existing or new applications. Natu-rally, we need to ensure that an enzyme discovered in the laboratory will work well at our customers! And one of the major challenges in discovering new enzymes is the gap between lab scale and real life industrial scale.
In order to find an enzyme with the desired properties needed for commercial success we often need to look through thousands, or for protein engineered enzymes even millions of new enzymes. It is impossible - and impractical - to test all of these enzymes in the final application. Downscaling and simplification is needed to increase the number of tests that can be carried out in a given time frame.
But how does one simplify the industrial process conditions to a level where it can be transferred to lab scale and still reflect the critical reallife problems? This is more difficult than it may seem. How do you know when a given enzyme makes cleaner clothes without washing them in a washing machine? How do you know the crumb structure of bread will improve without baking real bread? How do you know an enzyme will reduce phosphate content of the manure from piglets without feeding trials? How do you know an enzyme will improve colouring and wetting properties of cotton fabric or yarn without trying it out in a textile mill?
The trick is to design the tests in a way, which reflect the desired process conditions and simultane-ously puts a strong selection pressure on the different enzymes in the pool. Only the relevant enzymes should show activity. Preferably it is possible to design a test in microtiter plates, which correlates strongly with the real life problem. But most often a cascade of tests are required, each having a higher correlation with the industrial application, resembles real life application more but with increasing time consumption and reduced test capacity.
The first level of testing is done in microtiter plates or agar plates. The microorganisms may grow di-rectly on the agar plate or in the microtiter plate, and the secreted enzymes are tested insitu. Poor and medio performing enzymes should be deselected as soon as possible. The top performing en-zymes are tested in assays with better correlation.
An example is in the detergent area. Small pieces of fabrics soiled with a relevant soil are placed in the microtiter plate. In a robotic screening the enzymes are ranked according to how well they can release the dirt from the fabric in these wells. A real detergent base is used as in real life washing (as the buffer solution). The best enzymes are fermented and purified in an amount sufficient for washing trials in 50-200 ml scale. In this system the mechanical agitation of washing machines can be mimicked, and better correlation to real washing machines is obtained. The final tests with the few best enzymes - before choosing one for launch - are done in full-scale washing machines on regular soiled fabrics.
Novozymes has experienced this conflict between correlation and test-capacity in decades, and our worldclass ability to deal with this challenge is a key to Novozymes success. The better the downscaled test correlates with the real industrial application, the faster and cheaper is the development, and the likelihood of filing patent applications faster then competition increases.
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