Miniaturization in biotechnology: Speeding up the development of bioprocesses

Recent Patents on Biotechnology

Volumn 5, Issue 3, 2011, Pages 160-173

  Fernandes, Pedro ^a,b   Carvalho, Filipe ^a,b   Marques, Marco P C ^a,b  

^a INSTITUTO SUPERIOR TÉCNICO   (Portugal)

^b Instituto de Biotecnologia e Bioengenharia Lisboa   (Portugal)

Author keywords

Automation; Biocatalysis; Downstream processing; Fermentation; High throughput; Microfluidic devices; Microreactors; Microsensors; Microstructured reactors; Microtiter plates; Miniature bioreactors; Miniaturization in biotechnology; Monitoring and control of process variables; Optodes; Process intensification; Shaken vessels

Indexed keywords

BIOREACTORS; BIOTECHNOLOGY; FERMENTATION; MICROSENSORS; MINIATURE INSTRUMENTS;

BIOCATALYSIS; DOWNSTREAM-PROCESSING; HIGH-THROUGHPUT; MICRO-REACTOR; MICROFLUIDICS DEVICES; MICROSTRUCTURED REACTORS; MICROTITER PLATES; MINIATURE BIOREACTOR; MINIATURISATION; MINIATURIZATION IN BIOTECHNOLOGY; MONITORING AND CONTROL; MONITORING AND CONTROL OF PROCESS VARIABLE; OPTODES; PROCESS INTENSIFICATION; PROCESS VARIABLES; SHAKEN VESSEL;

MICROFLUIDICS;

ANALYTIC METHOD; AUTOMATION; BIOPROCESS; BIOREACTOR; BIOTECHNOLOGY; CHROMATOGRAPHY; DOWNSTREAM PROCESSING; ELECTRONICS; EQUIPMENT; EVAPORATION; FERMENTATION OPTIMIZATION; HIGH THROUGHPUT SCREENING; MICROFLUIDICS; MICROREACTOR; MICROTITER PLATE ASSAY; NONHUMAN; ONLINE MONITORING; PRIORITY JOURNAL; PROCESS CONTROL; PROCESS DEVELOPMENT; PROCESS MONITORING; REVIEW; SCALE UP; SHAKEN VESSEL;

EID: 80054124219     PISSN: 18722083     EISSN: None     Source Type: Journal    
DOI: 10.2174/187220811797579105     Document Type: Review

References (179)

1. Wohlgemuth R. Biocatalysis - key to sustainable industrial chemistry. Curr Opin Biotechnol 2010; 21: 713-24.
2. Jiménez-González C, Woodley JM. Bioprocesses: Modeling needs for process evaluation and sustainability assessment. Computers Chem Eng 2010; 34: 1009-17.
3. Clark JH, Deswarte FEI, Farmer TJ. The integration of green chemistry into future biorefineries. Biofuels Bioprod Bioref 2009; 3:72-90.
4. Wohlgemuth R. The locks and keys to industrial biotechnology. New Biotechnol 2009; 25: 204-13.
5. Bareither R, Pollard D. A review of advanced small-scale parallel bioreactor technology for accelerated process development: current state and future need. Biotechnol Prog 2011; 27: 2-14.
6. Fernandes P. Miniaturization in biocatalysis. Int J Mol Sci 2010; 11: 858-879
7. Marques MPC, Cabral JMS, Fernandes P. High throughput in biotechnology: from shake-flasks to fully instrumented microfermentors. Recent Pat Biotechnol 2009; 3: 124-40.
8. Schäpper D, Alam MN, Szita N, Eliasson Lantz A, Gernaey KV. Application of microbioreactors in fermentation process development: a review. Anal Bioanal Chem 2009; 395: 679-95.
9. Zimmermann HF, John GT, Trauthwein H, Dingerdissen U, Huthmacher K. Rapid evaluation of oxygen and water permeation through microplate sealing tapes. Biotechnol Prog 2003; 19: 1061-3.
10. Duetz WA. Microtiter plates as mini-bioreactors: Miniaturization of fermentation methods. Trends Microbiol 2007; 15: 469-75.
11. Schreiber R, Altenburger R, Paschke A, Küster E. How to deal with lipophilic and volatile organic substances in microtiter plate assays. Environ Toxicol Chem 2008; 27: 1676-82.
12. Ireland RM. Multi-well plate closure. GB2322121, 1998.
13. System Duetz" - Oxygen transfer rates. Available at: http://www.enzyscreen.com/1551010.htm (Accessed on: July 27, 2011).
14. Tyndorf TA, Cannataro R. Closed system storage plates. EP 1302243, 2003.
15. Treptow R. Cover sheet for a microtitre plate. US 20100028211, 2010.
16. Marques MPC, Carvalho F, Magalhães S, Cabral JMS, Fernandes P. Screening for suitable solvents as substrate carriers for the microbial side-chain cleavage of sitosterol using microtitre plates. Process Biochem 2009; 44: 556-61.
17. Marques MP, de Carvalho CC, Cabral JM, Fernandes P. Scaling-up of complex whole-cell bioconversions in conventional and nonconventional media. Biotechnol Bioeng 2010; 106: 619-26.
18. Schreiber R, Altenburger R, Paschke A, Küster E. How to deal with lipophilic and volatile organic substances in microtiter plate assays. Environ Toxicol Chem 2008; 27: 1676-82.
19. Funke M, Buchenauer A, Schnakenberg U, et al. Microfluidic biolector-microfluidic bioprocess control in microtiter plates. Biotechnol Bioeng 2010; 107: 497-505.
20. Funke M, Buchenauer A, Mokwa W, et al. Bioprocess control in microscale: scalable fermentations in disposable and user-friendly microfluidic systems. Microb Cell Fact 2010; 9: 86-98.
21. Kensy F, Mueller C, Büchs J, Funke M. Microreactor. US 20100248995, 2010.
22. m2p-labs - from microreactor to process. Available at: http://www.m2p-labs.com (Assessed on: June 13, 2011).
23. Funke, M, Diederichs S, Kensy F, Müller C, Büchs J. The Baffled Microtiter Plate: Increased OxygenTransfer and Improved Online Monitoring in Small Scale Fermentations. Biotechnol. Bioeng 2009; 103:1118-1128.
24. Herrmann MG, Sandrock TM. The 104-Well Microplate. JALA 2011; 16:214-20.
25. Vollert H. Miniaturized microtiter plate for HT-screening. US20090104081, 2009.
26. PreSens Precision sensing - Sensors for industry & research. Available at: http://www.presens.de (Assessed on: June 12, 2011).
27. Rhee JI, Sohn O-J. Multi-Channel Bioreactor with the Immobillization of Optical Sensing Membrane. US 20100297744, 2010.
28. Markle DR, Suri JT, Wessling RA, Romey MA. Optical determination of pH and glucose. US 20100274110, 2010.
29. Rhee JI, Kim C-K, Sohn O-J. Optical sensing membranes, devices and methods for simultaneous etection of two or more parameters of dissolved oxygen concentration, pH and temperature. US 20100279428, 2010.
30. Isett K, George H, Herber W, Amanullah A. Twenty-four-well plate miniature bioreactor high-throughput system: Assessment for microbial cultivations. Biotechnol Bioeng 2007; 98: 1017-28.
31. Huber R, Roth S, Rahmen N, Büchs J. Utilizing high-throughput experimentation to enhance specific productivity of an E.coli T7 expression system by phosphate limitation. BMC Biotechnol 2011; 11: 22-32.
32. Chen A, Chitta R, Chang D, Amanullah A. Twenty-four well plate miniature bioreactor system as a scale-down model for cell culture process development. Biotechnol Bioeng 2009; 102: 148-60.
33. Pall Corporation - Bioreactors and Microbioreactors. Available at: http://www.pall.com/biopharm_52976.asp (assessed on: June 13, 2011)
34. van Praet P. Led densitometer for microtiter plate. WO 2011008299, 2011.
35. de Carvalho CCCR, Marques MPC, Fernandes P, da Fonseca MMR A simple imaging method for biomass determination. J Microbiol Meth 2005; 60: 135-40.
36. Duetz WA. An apparatus and a method for investigation of microtiter platez subjected to orbital shaking. WO 2010037862, 2010.
37. Huber R, Ritter D, Hering T, et al. Robo-Lector - a novel platform for automated high-throughput cultivations in microtiter plates with high information content. Microb Cell Fact 2009; 8: 42-56.
38. Silbert R, Capella R, Cuzens J. Integrated robotic sample transfer device. WO 2009039122, 2009.
39. Rizzote SH, Avgerinos PN, Turner DA. Robotic grip and twist assembly. US 20100119413, 2010.
40. Buchenauer A, Hofmann MC, Funke M, Büchs J, Mokwa W, Schnakenberg U. Micro-bioreactors for fed-batch fermentations with integrated online monitoring and microfluidic devices. Biosensors Bioelectron 2009; 24: 1411-6.
41. Puntambekar A, Kai J, Lee SH, Ahn CH. Microfluidic assay platforms. WO 2011011350, 2011.
42. Mueller C, Klammer I, Kensy F, et al, Krefeld WA. Microreactor array, device comprising a microreactor array and method for using a microreactor array. US20090320622, 2010.
43. Microtiter Plates with Integrated Microcapillary Structures. Available at: http://www.greinerbioone.com/en/france/articles/literatures/publications/ (Assessed on. June 16, 2011).
44. van Leeuwen M, Buijs NAA, Canelas AB, Oudshoorn A, Heijnen JJ, van Gulik WM. The Hagen-Poiseuille pump for parallel fedbatch cultivations in microbioreactors. Chem Eng Sci 2009; 64: 1877-84.
45. Jeude M, Dittrich B, Niederschulte H, et al. Fed-batch mode in shake flasks by slow-release technique. Biotechnol Bioeng 2006; 95: 433-45.
46. Büchs J, Klee D, Dittrich B, Jeude M. Fermentation Method and Apparatus for its Implementation. US 20090104655, 2009.
47. Vasala A, Neubauer P, Panula-Perala J. Method for controlling the growth of cell culture. US 20100099164, 2010
48. Kuhner Shaker - Slow release technology: FeedBeads. Available at: http://www.kuhner.com/home-shaker/applied-technologies/slow-release-technology. (Assessed on: June 12, 2011).
49. Scheidle M, Dittrich B, Klinger J, Ikeda H, Klee D, Büchs J. Controlling pH in shake flasks using polymer-based controlled-release discs with pre-determined release kinetics. BMC Biotechnol 2011; 11: 25-35.
50. Panula-Perälä J, Siurkus J, Vasala A, Wilmanowski R, Casteleijn MG, Neubauer P. Enzyme controlled glucose auto-delivery for high cell density cultivations in microplates and shake flasks. Microbial Cell Factories 2008; 7: 31-42.
51. BioSilta - the company behnd EnBase. Available at: http://www.biosilta.com/about_biosilta.php (Assessed on: June 12, 2011).
52. Siurkus J, Panula-Perälä J, Horn U, Kraft M, Rimseliene R, Neubauer P. Novel approach of high cell density recombinant bioprocess development: optimisation and scale-up from microliter to pilot scales while maintaining the fed-batch cultivation mode of E. coli cultures. Microb Cell Fact 2010; 9: 35-51.
53. Krause M, Ukkonen K, Haataja T, et al. A novel fed-batch based cultivation method provides high cell-density and improves yield of soluble recombinant proteins in shaken cultures. Microb Cell Fact 2010; 9: 11-.21.
54. Sedletsky JM. Process Development and Scale-up from Shake Flask to Fermenter of Suspended and Immobilized Aerobic Microorganisms. PhD thesis. RWTH Aachen University. Aachen, Germany, 2007.
55. Marques MPC, Cabral JMS, Fernandes P. A microwell platform for the scale-up of a multistep bioconversion to bench-scale reactors: Sitosterol side-chain cleavage. Biotechnol J 2010; 5: 402-12.
56. Zawada JF, Yin G, Steiner AR, Yang et al. Microscale to manufacturing scale-up of cell-free cytokine production-a new approach for shortening protein production development timelines. Biotechnol Bioeng 2011; 108: 1570-8.
57. Zarur AJ, Rodgers ST. Microreactor simulation of microreactor. WO 2006066002, 2006
58. Bragos RB, Rossell XF, Riu JPC, et al. Modular system comprising automated mini-bioreactors for high-throughput screening (HTS) in biotechnology. EP 1580261 B1, 2010.
59. Hortsch R, Weuster-Botz D. Milliliter-scale stirred tank reactors for the cultivation of microorganisms. Adv Appl Microbiol. 2010; 73: 61-82.
60. th IEEE EMBS Annual International Conference. New York City, USA, Aug 30-Sept 3, 2006.
61. Jaegle P. Microtiter plate with stirring elements. WO2008000312, 2008.
62. Mukhopadhyaya TK, Allison N, Charlton S, et al. Evaluation of anthrax vaccine production by Bacillus anthracis Sterne 34F2 in stirred suspension culture using a miniature bioreactor: A useful scale-down tool for studies on fermentations at high containment. Biochem Eng J 2010; 50: 139-44
63. Kloke A, Rubenwolf S, Bücking C, et al. A versatile miniature bioreactor and its application to bioelectrochemistry studies. Biosens Bioelectron 2010; 25: 2559-65.
64. Kusterer A, Krause C, Kaufmann K, Arnold M, Weuster-Botz D. Fully automated single-use stirred-tank bioreactors for parallel microbial cultivations. Bioprocess Biosyst Eng 2008; 31: 207-15.
65. Vester A, Hans M, Hohmann HP, Weuster-Botz D. Discrimination of riboflavin producing Bacillus subtilis strains based on their fedbatch process performances on a millilitre scale. Appl Microbiol Biotechnol 2009; 84: 71-6.
66. Hortsch R, Stratmann A, Weuster-Botz D. New milliliter-scale stirred tank bioreactors for the cultivation of mycelium forming microorganisms. Biotechnol Bioeng 2010; 106: 443-51.
67. Lamping SR, Zhang H, Allen B, Shamlou PA. Design of a prototype miniature bioreactor for high throughput automated bioprocessing. Chem Eng Sci 2003; 58: 747-758.
68. Betts JI, Doig SD, Baganz F. Characterization and application of a miniature 10 mL stirred-tank bioreactor, showing scale-down equivalence with a conventional 7 L reactor. Biotechnol Prog 2006; 22: 681-8.
69. Gill NK, Appleton M, Baganz F, Lye GJ. Design and characterization of a miniature stirred bioreactor system for parallel microbial fermentations. Biochem Eng Sci 2008; 39: 164-76
70. Gill NK, Appleton M, Lye GJ. Thermal profiling for parallel online monitoring of biomass growth in miniature stirred bioreactors. Biotechnol Lett 2008; 30:1571-5.
71. Gill NK, Appleton M, Baganz F, Lye GJ. Quantification of power consumption and oxygen transfer characteristics of a stirred miniature bioreactor for predictive fermentation scale-up. Biotechnol Bioeng 2008; 100: 1144-55.
72. Doig SD, Ortiz-Ochoa K, Ward JM, Baganz F. Characterization of oxygen transfer in miniature and lab-scale bubble column bioreactors and comparison of microbial growth performance based on constant k(L)a. Biotechnol Prog 2005; 21:1175-82.
73. Hortsch R, Weuster-Botz D. Power consumption and maximum energy dissipation in a milliliter-scale bioreactor. Biotechnol Prog 2010; 26: 595-9.
74. Applikon Biotechnology - Mini Bioreactors. Available at: http://www.applikon-bio.com/ (Assessed on: June 13, 2011)
75. DasGip - Parallel bioreactor systems for unparalleled results. Available at: http://www.dasgip.com/ (Assessed on: June 13, 2011)
76. ® Qplus. Available at: http://www.sartorius-stedim.com/index.php?id=5077 (Assessed on: June 13, 2011)
77. Medicel Cultivation Unit. Available at: http://www.bioresearchonline.com/product.mvc/Medicel-Cultivation-Unit-0002 (assessed on: June 13, 2011).
78. Biospectra - Clone Screener. Available at: http://www.biospectra.ch/clonescreener.html (Assessed on: June 13, 2011)
79. Andretta C. Multiple Bio-Reactor Device. US 2008095676, 2008
80. Fogale Biotech - Parallel bioreactor system. Available at: http://www.fogalebiotech.com/parallel-bioreactorsystem/fermentation (Assessed on: June 13, 2011)
81. Fluorometrix- Cellstation™ High Throughput Bioreactor. Available at: http://www.fluorometrix.com/products/htbr/ (Assessed on: June 20, 2011)
82. TAP Biosystems. Available at: http://www.tapbiosystems.com/a/micro-bioreactor-gp.htm (Assessed on: June 13, 2011).
83. Bhambure R, Kumar K, Rathore AS. High-throughput process development for biopharmaceutical drug substances. Trends Biotechnol 2011; 29: 127-35.
84. Zhang Z, Perozziello G, Boccazzi P, Sinskey AJ, Geschke O, Jensen KF. Microbioreactors for bioprocess development. JALA 2007; 12: 143-51.
85. Bolivar JM, Wiesbauer J, Nidetzky B. Biotransformations in microstructured reactors: more than flowing with the stream? Trends Biotechnol. 2011. Epub ahead of print. doi:10.1016/ j.tibtech.2011.03.005
86. Dudukovic MP. Reaction engineering: Status and future challenges. Chem Eng Sci 2010; 65: 3-11.
87. Saber M, Commenge JM, Falk L. Microreactor numbering-up in multi-scale networks for industrial-scale applications: Impact of flow maldistribution on the reactor performances. Chem Eng Sci 2010; 65: 372-9
88. Zhang Z, Boccazzi P, Choi H-G, Jensen KF, Sinskey AJ. Microbioreactor for continuous cellculture. WO2007038572, 2007.
89. Zhang Z., Boccazzi P, Choi H-g, Jensen KF, Sinskey AJ. Microbioreactor for continuous cell culture. WO2007038572, 2007.
90. Jähnisch K, Hessel V, Löwe H, Baerns M. Chemistry in microstructured reactors. Angew Chem Int Ed Engl 2004; 43: 406-46.
91. Illg T, Löb P, Hessel V. Flow chemistry using milli- and microstructured reactors-from conventional to novel process windows. Bioorg Med Chem. 2010; 18: 3707-19.
92. Krommenhoek EE, Gardeniers JG, Bomer JG, et al. Integrated electrochemical sensor array for on-line monitoring of yeast fermentations. Anal Chem 2007; 79: 5567-73.
93. Krommenhoek EE, van Leeuwen M, Gardeniers H, et al. Lab-scale fermentation tests of microchip with integrated electrochemical sensors for pH, temperature, dissolved oxygen and viable biomass concentration. Biotechnol Bioeng 2008; 99: 884-92.
94. van Leeuwen M, Krommenhoek EE, Heijnen JJ, Gardeniers H, van der Wielen LA, van Gulik WM. Aerobic batch cultivation in micro bioreactor with integrated electrochemical sensor array. Biotechnol Prog 2010; 26: 293-300.
95. van Leeuwen M, Heijnen JJ, Gardeniers H, van der Wielen LA, van Gulik WM. Development of a system for the on-line measurement of carbon dioxide production in microbioreactors: application to aerobic batch cultivations of Candida utilis. Biotechnol Prog 2009; 25: 892-7.
96. Miyazaki M, Honda T, Yamaguchi H, Briones MPP, Maeda H. Enzymatic processing in microfluidic reactors. Biotechnol Gen Eng Rev 2008; 25: 405-428.
97. Gokhale SV, Tayal RK, Jayaraman VK, Kulkarni BD. Microchannel reactors: Applications and use in process development. Int J Chem React Eng 2005; 3: 1-53.
98. Gascon H, Duisit G, Brunet E. Process for fabricating a microfluidic device. US 20100043494, 2010.
99. Jambovanne S, Duin EC, Kim S-K, Hong JW. Deteermination of kinetic parameters, Km and kcat, with a single experiment on a chip. Anal Chem 2009; 81: 3239-45.
100. Jury AJ, Angelino MD. Microreactor. WO20090275115, 2009.
101. Tisma M, Zelic B, Vasic-Racki D, Znidarsic-Plazl P, Plazl I. Modelling of laccase-catalyzed l-DOPA oxidation in amicroreactor. Chem Eng J 2009; 149: 383-8.
102. Pohar A, Plazl I, Znidarsic-Plazl P. Lipase-catalyzed synthesis of isoamyl acetate in an ionic liquid/n-heptane two-phase system at the microreactor scale. Lab Chip 2009; 9: 3385-90.
103. Thomsen MS, Nidetzky B. Coated-wall microreactor for continuous biocatalytic transformations using immobilized enzymes. Biotechnol J 2009; 4: 98-107.
104. Stojkovic G, Znidarsic-Plazl. Immobilization of Yeast Cells Within Microchannels of Different Materials. Acta Chim Slov 2010; 57, 144-9.
105. Stojkovic G, Plazl I, Znidarsic-Plazl. L-Malic acid production within a microreactor with surface immobilised fumarase. Microfluid Nanofluid 2011; 10: 627-35.
106. Costantini F, Benetti EM, Reinhoudt DN, Huskens J, Vancso GJ, Verboom W. Enzyme-functionalized polymer brush films on the inner wall of silicon-glass microreactors with tunable biocatalytic activity. Lab Chip 2010; 10: 3407-12.
107. Tudorache M, Mahalu D, Teodorescu C, Stand R, Bala C, Parvulescu VI. Biocatalytic microreactor incorporating HRP anchored on micro-/nano-lithographic patterns for flow oxidation of phenols. J Mol Catal B: Enzymatic 2011; 69: 133-9.
108. Schilke KF, Wilson KL, Cantrell T, Corti G, McIlroy DN, Kelly C. A novel enzymatic microreactor with Aspergillus oryzae β-galactosidase immobilized on silicon dioxide nanosprings. Biotechnol Prog 2010; 26: 1597-605.
109. Koh W-G, Pishko M. Immobilization of multi-enzyme microreactors inside microfluidic devices. Sensors Actuat B 2005; 106: 335-42.
110. Kataoka S, Endo A, Oyama M, Ohmori T. Enzymatic reactions inside a microreactor with a mesoporous silica catalyst support layer. Appl Catal A: General 2009; 359: 108-12.
111. Wu S, Ma J, Yang K, et al. A novel organic-inorganic hybrid monolith for trypsin immobilization. Sci China Life Sci 2011; 54:54-9.
112. Mugo SM, Ayton K. Lipase immobilized microstructured fiber based flow-through microreactor for facile lipid transformations. J Mol Catal B: Enzymatic 2010; 67: 202-7.
113. Matsuura S-i, Ishii R, Itoh R, et al. Immobilization of enzymeencapsulated nanoporous material in a microreactor and reaction analysis. Chem Eng J 2011; 167: 744-9.
114. Wiles C, Hammond MJ, Watts P. The development and evaluation of a continuous flow process for the lipase-mediate oxidation of alkenes. Beilstein J Org Chem 2009; 5: 27-38.
115. Kundu S, Bhangale AS, Wallace WE, et al. Continuous flow enzyme-catalyzed polymerization in a microreactor. J Am Chem Soc 2011; 133: 6006-11.
116. Karande R, Schmid A, Buehler K. Enzyme Catalysis in an Aqueous/Organic Segment Flow Microreactor: Ways to Stabilize Enzyme Activity. Langmuir 2010; 26: 9152-9.
117. Hickey AM, Ngamsom B, Wiles C, Greenway GM, Watts P, Littlechild JÁ. A microreactor for the study of biotransformations by a cross-linked γ-lactamase enzyme. Biotechnol J 2009; 4: 510-6.
118. Hotz N, Osterwalder N, Stark WJ, Bieri NR, Poulikakos D. Diskshaped packed bed micro-reactor for butane-to-syngas processing. Chem Eng Sci 2008; 63: 5193-201.
119. Blom MT, Mulder MC, Macinnes JM, Allen RWK. Micromixing Chamber, Micromixer Comprising a Plurality of Such Micromixing Chambers, Methods for Manufacturing Thereof, and Methods for Mixing. US20100067323, 2010.
120. Karp CD. Multi-stream microfluidic aperture mixers. US2003133358, 2003
121. Wang S-C, Chen H-P, Lee CY, Chang HC. Microfluidic mixer. US20080316854, 2008.
122. Wixforth A, Gauer C. Mixing deivce and mixing method for mixing small amounts of liquid. US20040115097, 2004
123. Swarts JW, Kolfschoten RC, Jansen MCAA, Janssen AEM, Boom RM. Effect of diffusion on enzyme activity in a microreactor. Chem Eng J 2010; 162: 301-6.
124. Li X, van der Steen G, van Dedem GWK, et al. Improving mixing in microbioreactors. Chem Eng Sci 2008; 63: 3036-46.
125. Pohar A, Plazl I. Process Intensification through Microreactor Application. Chem Biochem Eng Q 2009; 23: 537-44.
126. Krenkova J, Svec F. Less common applications of monoliths: IV. Recent developments in immobilized enzyme reactors for proteomics and biotechnology. J Sep Sci 2009; 32: 706-18.
127. Matosevic S, Szita N, Baganz F. Fundamentals and applications of immobilized microfluidic enzymatic reactors. J Chem Technol Biotechnol 2011; 86: 325-34.
128. Hessel V, Knobloch C, Löwe H. Review on Patents in Microreactor and Micro Process Engineering. Recent Pat Chem Eng 2008; 1: 1-16 1
129. Seahorse Bioscience - SimCell Technology. Available at: http://www.seahorsebio.com/bioprocessing/technology.php. (Assessed on: June 20, 2011)
130. Amanullah A, Otero JM, Mikola M, et al. Novel micro-bioreactor high throughput technology for cell culture process development: Reproducibility and scalability assessment of fed-batch CHO cultures. Biotechnol Bioeng 2010; 106: 57-7.
131. Future Chemistry. Available at: http://www.futurechemistry.com/. (Assessed on: June 20, 2011).
132. Micronit Microfluidics. Available at: http://www.micronit.com/ (Assessed on: June 20, 2011).
133. Oever R, Blom MT. Method for manufacturing and testing microfluidic chips. NL2003126, 2011.
134. Chemtrix BV. Available at: http://www.chemtrix.com/web/2/ company_profile.html. (Assessed on: June 20, 2011).
135. van de Heijden R. A micro-fluidic system and the use thereof. WO2010130368, 2010.
136. Microinnova. Available at: http://www.microinnova.com/ (Assessed on: June 20, 2011).
137. Dolomite. Available at: http://www.dolomite-microfluidics.com/ (Assessed on: June 27, 2011).
138. Syrris - Flow products. Available at: http://www.syrris.com/flowproducts (Assessed on: June 20, 2011).
139. Gilligan MPT, Homewood PJ, Whiffin R. A microreactor. EP1336432, 2003.
140. Gilligan MPT, Homewood PJ, Ranford RJ, Crisp PM. Modular microfluidic system. US20060150385, 2006.
141. Legmann R, Schreyer HB, Combs RG, McCormick EL, Russo AP, Rodgers ST. A predictive high-throughput scale-down model of monoclonal antibody production in CHO cells. Biotechnol Bioeng 2009; 104: 1107-20.
142. Wu MH, Huang SB, Cui Z, Cui Z, Lee GB. A high throughput perfusion-based microbioreactor platform integrated with pneumatic micropumps for three-dimensional cell culture. Biomed Microdevices. 2008; 10:309-19.
143. Wu MH, Lin JL, Wang J, Cui Z, Cui Z Development of high throughput optical sensor array for on-line pH monitoring in microscale cell culture environment. Biomed Microdevices. 2009; 11: 265-73.
144. Wu M-H, Huang S-B, Cui Z, Cui Z, Lee G-B. Development of perfusion-based micro 3-D cell culture platform and its application for high throughput drug testing Sensors Actuators B 2008; 129: 231-240
145. Wu MH, Wang HY, Liu HL, et al. Development of highthroughput perfusion-based microbioreactor platform capable of providing tunable dynamic tensile loading to cells and its application for the study of bovine articular chondrocytes. Biomed Microdevices 2011; 13: 789-98.
146. Lara AR, Galindo E, Ramirez OT, Palomares LA. Living with heterogeneous bioreactors: Understanding the effect of environmental gradients in cells. Mol Biotechnol 2006, 34;355-81.
147. De Mey M, Taymaz-Nikerel H, Baart G, et al. Catching prompt metabolite dynamics in Escherichia coli with the BioScope at oxygen rich conditions. Metab Eng 2010; 12:477-87.
148. Delvigne F, Ingels S, Thonart P. Evaluation of a set of E. coli reporter strains as physiological tracer for estimating bioreactor hydrodynamic efficiency. Process Biochem 2010; 45:1769-78.
149. Lara AR, Taymaz-Nikerel H, Mashego MR, et al. Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses. Biotechnol Bioeng 2009; 104:1153-61.
150. Taymaz-Nikerel H, van Gulik WM, Heijnen JJ. Escherichia coli responds with a rapid and large change in growth rate upon a shift from glucose-limited to glucose-excess conditions. Metab Eng 2011; 13: 307-18.
151. Titchener-Hooker NJ, Dunnill P, Hoare M. Micro biochemical engineering to accelerate the design of industrial-scale downstream processes for biopharmaceutical proteins. Biotechnol Bioeng 2008; 100: 473-87.
152. Rahul Bhambure, Kaushal Kumar and Anurag S. Rathore Highthroughput process development for biopharmaceutical drug substances. Trends Biotechnol 2011; 29: 127-35.
153. Zhou YH, Titchener-Hooker NJ. Visualizing integrated bioprocess designs through "windows of operation". Biotechnol Bioeng 1999; 65: 550-7.
154. Tustian AD, Salte H, Willoughby NA, et al. Adapted ultra scaledown approach for predicting the centrifugal separation behavior of high cell density cultures. Biotechnol Prog 2007; 23: 1404-10.
155. Tait AS, Aucamp JP, Bugeon A, Hoare M. Ultra scale-down prediction using microwell technology of the industrial scale clarification characteristics by centrifugation of mammalian cell broths. Biotechnol Bioeng 2009; 104: 321-31.
156. Jackson NB, Liddell JM, Lye GJ. An automated microscale technique for the quantitative and parallel analysis of microfiltration operations. J Memb Sci 2006; 276: 31-41.
157. Chhatre S, Titchener-Hooker NJ. Review: Microscale methods for high-throughput chromatography development in the pharmaceutical industry. J Chem Technol Biotechnol 2009; 84: 927-40.
158. Venn RF, Merson J, Cole S, Macrae P. 96-Well solid-phase extraction: a brief history of its development. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 5: 77-80.
159. Rege K, Heng M. Miniaturized parallel screens to identify chromatographic steps required for recombinant protein purification. Nature Protocols 2010; 5: 408-17.
160. Bensch M, Wierling PS, von Lieres E, Hubbuch J. High throughput screening of chromatographic phases for rapid process development. Chem Eng Technol 2005, 28: 1274-84.
161. Coffman JL, Kramarczyk JF, Kelley BD. High-throughput screening of chromatographic separations: I. Method development and column modeling. Biotechnol Bioeng 2008; 100: 605-18.
162. Kelley BD, Switzer M, Bastek P, et al. High-throughput screening of chromatographic separations: IV. Ion-exchange. Biotechnol Bioeng 2008; 100: 950-63.
163. Engstrand C, Rodrigo G, Forss A, Lacki K, Välimaa KN. Rapid and Scalable Microplate Development of a Two-Step Purification Process. BioProcess Int 2010; 8: 58-66.
164. Yoshimoto N, Nishijima Y, Akbarzadehlaleh P, Fujii S, Abe M, Yamamoto S. Micro-Plate Based Monolithic Ion-Exchange Chromatography for High Throughput Protein Purification Process Design. J Chem Eng Japan 2008; 41: 200-5.
165. Wenger MD, DePhillips P, Bracewell DG. A microscale yeast cell disruption technique for integrated process development strategies. Biotechnol Prog 2008; 24: 606-14.
166. Chhatre S, Francis R, Bracewell DG, Titchener-Hooker NJ. An automated packed protein G micro-pipette tip assay for rapid quantification of polyclonal antibodies in ovine serum. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878: 3067-75.
167. Chhatre S, Bracewell DG, Titchener-Hooker NJ. A microscale approach for predicting the performance of chromatography columns used to recover therapeutic polyclonal antibodies. J Chromatogr A 2009; 1216: 7806-15.
168. Kee GS, Jin J, Balasundaram B, Bracewell DG, Pujar NS, Titchener- Hooker NJ. Exploiting the intracellular compartmentalization characteristics of the S. cerevisiae host cell for enhancing primary purification of lipid-envelope virus-like particles. Biotechnol Prog 2010; 26: 26-33.
169. Wierling PS, Bogumil R, Knieps-Grünhagen E, Hubbuch J. High-Throughput Screening of Packed-Bed Chromatography Coupled With SELDI-TOF MS Analysis: Monoclonal Antibodies Versus Host Cell Protein. Biotechnol Bioeng 2007; 98: 440-50.
170. Brochier VB, Schapman A, Santambien P, Britsch L. Fast purification process optimization using mixed-mode chromatography sorbents in pre-packed mini-columns. J Chromatogr A 2008; 1177: 226-33.
171. Friedle J, Schroeder T. Automated small-scale parallel biochromatography. Availale on: http://www.iptonline.com/articles/public/Automated-Small-ScaleParallel-Biochroma-tography.pdf (Assessed on: June 22, 2011).
172. Huang J, Chou H-P, Unger MA. Microfluidic chromatography. US20050000900, 2005.
173. Huang J, Chou H-p, Unger MA. Microfluidic chromatography. US7217367, 2007
174. Shapiro MS, Haswell SJ, Lye GJ, Bracewell DG. Design and characterization of a microfluidic packed bed system for protein breakthrough and dynamic binding capacity determination. Biotechnol Prog 2009; 25: 277-85.
175. Shapiro MS, Haswell SJ, Lye GJ, Bracewell DG. Microfluidic Chromatography for Early Stage Evaluation of Biopharmaceutical Binding and Separation Conditions. Sep Sci Technol 2011; 46: 185-94.
176. Znidarsic-Plazl P, Plazl I. Steroid extraction in a microchannel system-mathematical modelling and Experiments. Lab Chip 2007, 7, 883-889.
177. Marques, M. P. Fernandes, P. Cabral, J. M. Znidarsic-Plazl, P. Plazl, I. On the feasibility of in situ steroid biotransformation and product recovery in microchannels. Chem Eng J 2010; 160: 708-14.
178. Gossett DR, Weaver WM, Mach AJ, et al. Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem 2010; 397: 3249-67.
179. Lenshof A, Laurell T. Continuous separation of cells and particles in microfluidic systems. Chem Soc Rev 2010; 39: 1203-17.