Phase partition and biotechnology continuous mode”‘. Partition coeffi- cients tvnicallv correlate with medi- Meeting tally ” ’ significant cell or macro- molecule alterations at the genetic report .~~~~~~~~~~~~~ The ideal separation method for commercial biotechnology should involve (FDA-approved) materials that are relatively inexpensive and recyclable, utilize little (electrical) ener‘gy, create minimal waste, adapt to existing hardware and processing systems, work for molecules as read- ily as particles, have chiral discrimi- nation and diagnostic potential, and be gentle enough to isolate complex protein systems, or viruses with intact coat structures. The method should also separate biomaterial on the basis of a variety of phenomena (e.g. par- ticle surface features and affinity interactions) under operator control. It should be easily automated, work over a wide range of temperatures, readily scale up (cm? to m3) without loss of resolution or process cost- efficiency, and handle concentrated (>20% w/w) product solutions. It should be understood theoretically, be amenable to predictive modeling, and not be ‘covered’ by patents. All these attributes describe aqueous polymer phase partition - ‘partition’. Last summer, over 80 scientists from 17 countries met in Zaragoza, Spain*, to celebrate partition enter- ing its 40th year, and to honor two scientists who are responsible for the technology. In 1955, a serendipitous graduate experiment led Per-kke Albertsson to discover the tech- nique’. His PhD thesis on the sub- ject is now in its third edition as a popular introductory text?. In 1963, Harry Walter entered the field. These two scientists have now con- tributed three books and over 200 publications to a partition literature that exceeds about 2000 journal articles1-3. This summer’s conference was the nintht on a technology of growing relevance to biotechnology. What follows provides an insight to partition and the work that was pre- sented in Zaragoza. Aqueous polymer phase partition Partition involves adding one or more neutral polymers to a buffered 0 1996, Elsevier Science Ltd 0167 - 7799/96/$15.00 TIBTECH JANUARY 1996 (VOL 14) salt solution, to effect its separation into two phases enriched in polymer or salt. Molecules such as proteins tend to partition differentially between the phases depending on size, conformation, charge (PI) and specific interactions with phase- forming polymers. Particles such as cells partition on the basis of various surface features and size, e.g. adsorp- tion at the phase interface. A single partition step simply involves adding the material of interest to a phase sys- tem, mixing gently and letting the system separate spontaneously as a result of phase-density differences. Many partition variables, including the ability to isolate substances on the basis of ionic or affinity interactions, are under operator control. Affinity interactions rely on micromolar amounts of polymer-derivatized ligands, including antibodies. Two or more discriminatory interactions often function simultaneously with impressive separations resulting from a few steps; for example, viruses can be concentrated 10(X-fold in two stages’. Multi-step chromatographic separations can be achieved by standard countercurrent or column- based methods. The latter expands resolution and in-line compatibihty by localizing one phase on a matrix eluted by the complementary phase’,‘. In addition to mild conditions of operation, simphcity, flexibility and resolving power, partition has a vari- ety of attributes that match the low- energy, large-scale, cost-efficient needs of modern biotechnology. Kecent publication+ document how- these attributes are now beconi- ing fully appreciated. Cell debris and nucleic acids often partition into a different phase from cell products, such as proteins. This makes partition an attractive primary purification step for operation in a t The 10th Intrrndtional l’xtition Confer- encr dl be organned by J. A. Asenjo and T. Treffrey. md ~11 be adtninistratwrly sponsored by the Society of Chemistry md Indurny (Brlgrave Syuarr, London. UK). It will be held in August 1097 At the Un~vrrs~ty of kadmg. UK. Infomntior~ on attrndmcr or mdustrial parncipmon cm be obtamed from J. A. Asrrjo (I~epartment of Chemical Enginwrinp, Univrrsldad dr Chile, Beauchef 861, Sanmgo, Chdr; Fax: +Sh 2 671 2709; EmuI: Juarenjo(~crc.uchile.cl). level, Target materials can, therefore. be chosen or modified to enhance their separation’-“. A. Veide and co- workers (Royal Institute of Tech- nology, Stockholm, Sweden) have shown that some genetically altered proteins exhibit a 50-fold increase in partition without loss of activitya,‘. R. A. Hart rt al. (Genentech, San Francisco, CA, USA) recently de- scribed the large-scale recovery of human insulinlike growth factor I (IGF-I) directly from urea-treated Erclzcvkhia co/i broth, using a poly- ethylene glycol (PEG) and sodium sulfate two-phase system. They achieved 70% recovery of 97% pure solubilized IGF-1 in the I’EG- emiched phase”. Towards a practical processing system Research topics covered at the Zaragoza Conference ranged from botany, to polymer solution physics, to the use of partition for the recov- ery and concentration of radioactive waste materials. As in the past. papers from the meeting will be published in a special edition of the ]o~rr~al O$ C/zro~zat~~ru$zy~. What follows notes conference presentations of research of biotechnological interest. E. L. Braunstein, N. T. Becker and G. Ganshaw (Genencor Intcr- national, Rochester, NY. USA), presented work on the development of a cost-effective process for the single-step industrial extraction of enzymes (e.g. hydrophobic lipases and hydrophilic proteases) used in detergent formulations. The tech- nique involved using a phase in which surtactant was substituted for PEG. T. Minuth, J. Th6mmec and M-R. Kula (Institute for Enzyme Technology, Heinrich-Heine- University, IXisseldorf Gcmiany) detailed the use of PEG-based phase systems containing non-ionic detergent for the downstream processing of amphiphilic proteins, such as cholesterol oxidase from A’. vhodoch vo us. Much work is being done in Sweden to enhance the general capabilities of the phase systems. F. Tjemeld et al. (University oflund) are working to optimize component recycling and separation efficiency, while G. Johansson cf al., also at Lund, are using organic additives to extend system operating temperatures down