近十年来原位分离技术在生物工程领域的发展

1、1Advances in in-situ product recovery(ISPR) in whole cell biotechnology during the last decade2lIntroductionlAdvantages of ISPRlRequirementslSupporting technologies/enabling tools3Introduction about this review 1.Reasons The product inhibition and the side reactions lead to substantial downstream pr

2、ocessing costs, high waste water volumes, high fermentor costs and an increased substrate cost.so we invest the in-situ product recovery(ISPR) to sove these problems. The rationales a.enrich the product leading to a decrease in downstream processing costs; b. improve the volumetric productivity by a

3、lleviation of product inhibition; c. reduce the process flows(decrease amount of waste water per weight unit of product); d.improve the yield by removing the target product from the fermentation broth ISPR is not only used to remove the target product but also used to separate inhibitory by-products

4、.42.Including of the review The review presents the state-of-the-art in the applications of in-situ product recovery (ISPR) in whole-cell biotechnology over the last 10 years. Several reviews focus on a particular ISPR technique such as pervaporation, extraction, gas stripping,absorption,and ion exc

5、hange. All operational modes of cell cultivation (batch, fed-batch and continuous) and all ISPR techniques are considered. Processes using isolated enzymes or plant and animal cell cultures are kept outof scope for this review.53.Trends in ISPR applications over the last 10 years In the past 10 year

6、s, about 140 papers have been published which describe fermentations coupled with ISPR technology.6 Different configurations of ISPR are possible depending on the location of the separation unit. The selection of the proper ISPR technology are important.7a solventslThe reviews of ISPR technologies c

7、oupled to a fermentation for acetone butanol ethanol (ABE) fermentation easily surpassed the reviews of ISPR research related to ethanol in the last decades.lIsobutanol is a newcomer on the list and has been industrially implemented with a capacity of 68*106 L.lA gradual shift could be noted from ba

8、tch to fed-batch to continuous mode of operation.lThe most investigated ISPR techniques were gas stripping, organophilic pervaporation,and liquidliquid extraction.lThe internal-direct ISPR configuration was used predominantly.8b organic acidslThe second important class of products for which ISPR had

9、 been extensively used was organic acids, accounting for 21% of the reports.lThe ISPR techniques most frequently applied were electrodialysis and ion exchange.l47% of the articles reported the use of an external indirect configuration on application of electrodialysis.lthe membrane stack of an elect

10、rodialysis unit can easily be clogged by the particles present in the fermentation broth.lIon exchange processes were tested in equal numbers in the external direct or indirect mode.9c fragrances/flavors and other products lThe main reason to apply ISPR was to protect the desired product from furthe

11、rdegradation reactions.lThe target for ISPR in production of recombinant proteins and enzymes, wasusually also an organic acid.lAbout 72% of the ISPR configurations was of the ID type which could be attributed to the techniques applied, i.e. extraction and to some extent sorption. We expect that the

12、 shift from batch to continuous configurations already observed in the alcohol/solvents class will proceed for the other product classes as well.10Advantages of ISPR1.Product enrichment A two-stage gas stripping technique wherein a firststage condensate was further stripped to produce a condensate c

13、oncentration of 420 gL 1 in the second stage. The concentrations have not been high enough to demonstrate the benefit of ISPR using membrane distillation for increased product titers as compared to conventional ethanol fermentations. Etschmann and Schrader obtained 26.5 gL 1 2-phenylethanol in polyp

14、ropylene glycol 1200 as organic extractant for a fed-batch process using a concentrated feed of 600 gL 1 glucose. The improvements in concentrations of recombinant proteins amounted to only 1015% as compared to non-ISPR processes.112.Increased productivity Removal of inhibitory product from the ferm

15、entation broth relieves the inhibition on cells which consequently leads to higher cell growth and product formation rates. Inhibition by an organic acid on cell growth can be described by the Levenspiels model with Monod equation 123.Reduced process flows/increased substrate concentration Another a

16、dvantage of ISPR is the utilization of highly concentratedsubstrate. Usage of high initial glucose concentrations of up to 162 gL-1 i.e.2.7-fold higher than concentrations used in conventional batch for ABE fermentation (60 gL1) using gas stripping was reported . The complete utilization of highly c

17、oncentrated feed containing 300 gL-1 glucose for high lactic acid production (185 gL-1 ) in a fed-batch fermentation.134.Improved yield Three possible reasons could be hypothesized for yield increase a) use of highly concentrated feed allowing greater turnover to product than utilization for biomass

18、 formation. b) relieving the stress on the microorganism by removal of the inhibitory component leading to decreased intracellular maintenance. c) increasing the yield of an unstable product by rendering it unavailable for further metabolism and formation of other products.14RequirementsSeveral requ

19、irements can be formulated for industrial implementation about ISPR 1. keep the technology as simple as possible to allow a straightforward upscaling; 2. demonstrate long term robustness and stability of the integrated test set-up; 3. demonstrate decreased energy consumption of integrated design; 4.

20、 elaborate process design with maximum product recovery; 5. perform techno-economic assessments of integrated design.1.Scalability Bringing ISPR technology from lab scale to pilot and production plant requires an in-depth interaction between chemical engineering, biotechnology and entrepreneurialism

21、.152.Long term robustness and stability In order to be considered for implementation,the long-term performance and stability of an ISPR technology need to be demonstrated. Continuous operation offers several advantages from a chemical engineers point-of-view However, from a biological point-of-view

22、it should be mentioned that a long ISPR operation also increases the chances of contamination and strain instability or degeneration. Trade-offs need to be carefully evaluated. While lower product titers in the fermentor would lead to better process performance by alleviation of product inhibition and product degradation, higher concentrations would be beneficial for recovery technologies with limited separation factors.163.Maximum product recovery A continuous process for