 My name is Marcel Oltens, still at the University of Technology and I'm Batman 4 and I post up at the Bethany University of Technology. So the question is how to develop approaches in downstream processing. So there are several approaches that you could use. The traditional approaches, the normal approaches where high throughput screening, for example issues, but also knowledge based approaches. And in practice, platform approaches are being used, but they have also their pros and cons. It's not easy to apply that to a completely new type of product. So what we developed here in Delft is a knowledge based, pros and develop approach. What you can see here at the bottom of it is modeling, modeling the different unit operations. But for that we need also a lot of data of the modules that we try to separate. So we need to come up with a fractionation and characterization scheme that describes the modules and their interaction with the different resins that we use during processing. This paper is about investigating this route, this fractionation and characterization route. And the approach that is taken will be subsequently explained by our post of Bethany University. The multidimensional fractionation and characterization scheme was designed to obtain molecular properties descriptors required for protein purification from crude biological mixtures using non-affinity chromatographic techniques such as ion exchange chromatography, hydrophobic interaction chromatography, and size excretion chromatography. First, the crude biological mixture is fractionated in a high resolution pH gradient ion exchange operation. Results from pH gradient operation provides information on the complexity of the crude biological mixture as well as the emission pH and emission conductivities of the major proteins. Having obtained the most optimal chromatographic absorbance and operating conditions by means of high throughput screening the crude biological mixture is further fractionated in salt gradient ion exchange operations. Data obtained from these salt gradient operations is used for the regression of ion exchange isophan parameters. Fractions from salt gradient fractionation are further injected into the heat dimension after adjustment of conductivity. Similarly, data obtained from the HEC operation are used for regressing the HEC isotope parameters. Next, the fractions from the ion exchange, cation exchange, and HEC operations are further disorted, pre-concentrated, and analyzed by SDS page. SDS page provides information on the molecular size and relative concentrations of the major protein bands. The major protein bands are densiplized, triptych-digested, and analyzed by mass spectrometry to obtain the unique protein identities. Finally, a molecular property database is settled by assigning the obtained molecular properties to the identified proteins. Now, once the molecular property database has been settled, then it can be applied to introduce more rationale in downstream process development. One application of this is for identification of the critical contaminants in the protein mixture. By critical contaminants, I refer here to contaminants that are most troublesome to remove, mainly because they have very close physical chemical properties to the target molecule. Now, by identifying and characterizing these critical contaminants, we can actually find more suitable techniques for the eye removal. In current downstream process development, process synthesis is mainly a heuristic task whereby unit operations are used based on experience. Molecular properties descriptors could be used for introducing more rationale in downstream process synthesis, as exemplified in this paper. Another approach is to use these molecular properties descriptors as input for more detailed modeling of the downstream process unit operations. In this way, the unit operations can be optimized and evaluated in silico, thereby saving experimental time, material and cost. So, concluding the future of this approach lies in further miniaturization, automation, eye focus screening and novel analytical tools development.