Chemical and physical processes for integrated temperature control in microfluidic devices

Microfluidic devices are a promising new tool for studying and optimizing (bio)chemical reactions and analyses. Many (bio)chemical reactions require accurate temperature control, such as for example thermocycling for PCR. Here, a new integrated temperature control system for microfluidic devices is presented, using chemical and physical processes to locally regulate temperature. In demonstration experiments, the evaporation of acetone was used as an endothermic process to cool a microchannel. Additionally, heating of a microchannel was achieved by dissolution of concentrated sulfuric acid in water as an exothermic process. Localization of the contact area of two flows in a microfluidic channel allows control of the position and the magnitude of the thermal effect. © The Royal Society of Chemistry 2003

Considerations on contactless conductivity detection in capillary electrophoresis

Nearly all analyses by capillary electrophoresis (CE) are performed using optical detection, utilizing either absorbance or (laser-induced) fluorescence. Though adequate for many analytical problems, in a large number of cases, e.g., involving non-UV-absorbing compounds, these optical detection methods fall short. Indirect optical detection can then still provide an acceptable means of detection, however, with a strongly reduced sensitivity. During the past few years, contactless conductivity detection (CCD) has been presented as a valuable extension to optical detection techniques. It has been demonstrated that with CCD detection limits comparable, or even superior, to (indirect) optical detection can be obtained. Additionally, construction of the CCD around the CE capillary is straightforward and robust operation is easily obtained. Unfortunately, in the literature a large variety of designs and operating conditions for CCD were described. In this contribution, several important parameters of CCD are identified and their influence on, e.g., detectability and peak shape is described. An optimized setup based on a well-defined detection cell with three detection electrodes is presented. Additionally, simple and commercially available read-out electronics are described. The performance of the CCD-CE system was demonstrated for the analysis of peptides. Detection limits at the μM level were obtained in combination with good peak shapes and an overall good performance and stability

Design strategies for integrated protein purification processes: challenges, progress and outlook

The key to successful and efficient protein purification is the selection of the most appropriate purification techniques and their combination in a logical way to obtain the desired purification in the minimum number of steps. However, the rationalization of protein purification process development is faced with a number of challenges. In this paper, the challenges in protein purification process development are captured. The state-of-the-art in protein purification process synthesis and design is reviewed and the strengths and weaknesses of the current strategies highlighted. Finally, views on the future directions of protein purification process development are presente

Design strategies for integrated protein purification processes: challenges, progress and outlook

The key to successful and efficient protein purification is the selection of the most appropriate purification techniques and their combination in a logical way to obtain the desired purification in the minimum number of steps. However, the rationalization of protein purification process development is faced with a number of challenges. In this paper, the challenges in protein purification process development are captured. The state-of-the-art in protein purification process synthesis and design is reviewed and the strengths and weaknesses of the current strategies highlighted. Finally, views on the future directions of protein purification process development are presente

Design strategies for integrated protein purification processes: challenges, progress and outlook

The key to successful and efficient protein purification is the selection of the most appropriate purification techniques and their combination in a logical way to obtain the desired purification in the minimum number of steps. However, the rationalization of protein purification process development is faced with a number of challenges. In this paper, the challenges in protein purification process development are captured. The state-of-the-art in protein purification process synthesis and design is reviewed and the strengths and weaknesses of the current strategies highlighted. Finally, views on the future directions of protein purification process development are presente

Model-based rational methodology for protein purification process synthesis

A model-basedrationalproteinpurificationprocesssynthesismethodologythataddressesthe challengeofselectingthemostoptimalprocessschemefromseveralpossiblealternativesispresented in thisstudy.Themainrationalebehindthemethodologyistokeepthenumberofpurificationunitsin the finalprocesstotheminimumthroughasystematiccycleofflowsheetsynthesis,optimization, evaluationandtherationaleliminationoftheleastfeasibleprocessoptionsateachpurificationstep, takingintoaccountthespecificneedsofthepurificationstep.Processevaluationisbasedontechno- economicperformanceobtainedbymodel-basedoptimizationoftheintegratedprocessesusing validatedcolumnmodels.Themethodologywasillustratedbysynthesizingaprocessforthe purificationofmonoclonalantibodyfromcrudehybridomacellculturesupernatantusingfournon- affinitychromatographicmethods(AEX,CEX,SECandHIC).Theresultsshowedthatfouroutofthirteen evaluatedprocessoptionssatisfiedallpre-definedproductspecifications,withoverallyields Z90%. In order ofincreasingproductcost,thesewereCEX–AEXoAEX–CEXoAEX–HICoHIC–AEX,takinginto accounttheneedforinter-stageconditioning.Themainadvantagesofthemethodologyincludesavings in experimentation,computationaltimeandeffort;unbiasedevaluationofpurificationschemesby using theiridealoperatingconditions;andtheconsiderationofthespecificneedsofeachpurification step duringprocessevaluation.Finally,themethodologyisgenericforcell-derivedproteins,irrespec- tive ofthehostorganismorapplication