For better control of productivity and product quality, detailed monitoring of various parameters is required. Since disposable bioreactors become more and more important for biotechnological applications, adequate sensors for this type of reactor are necessary. The required properties of sensors used in disposable reactors differ from those of sensors for multiuse reactors. For example, sensors which are in direct contact with the medium must be inexpensive, but do not need a long life-time, since they can be used only once.This chapter gives an overview on the state of the art and future trends in the field of sensors suited for use in disposable bioreactors. The main focus here is on in situ sensors, which can be based on optical, semiconductor and ultrasonic technologies, but current concepts for disposable sampling units are also reviewed.

Over the last two decades, more and more applications of sophisticated sensor technology have been described in the literature on upstreaming and downstreaming for biotechnological processes (Middendorf et al. J Biotechnol 31:395-403, 1993; Lausch et al. J Chromatogr A 654:190-195, 1993; Scheper et al. Ann NY Acad Sci 506:431-445, 1987), in order to improve the quality and stability of these processes. Generally, biotechnological processes consist of complex three-phase systems--the cells (solid phase) are suspended in medium (liquid phase) and will be streamed by a gas phase. The chemical analysis of such processes has to observe all three phases. Furthermore, the bioanalytical processes used must monitor physical process values (e.g. temperature, shear force), chemical process values (e.g. pH), and biological process values (metabolic state of cell, morphology). In particular, for monitoring and estimation of relevant biological process variables, image-based inline sensors are used increasingly. Of special interest are sensors which can be installed in a bioreactor as sensor probes (e.g. pH probe). The cultivation medium is directly monitored in the process without any need for withdrawal of samples or bypassing. Important variables for the control of such processes are cell count, cell-size distribution (CSD), and the morphology of cells (Höpfner et al. Bioprocess Biosyst Eng 33:247-256, 2010). A major impetus for the development of these image-based techniques is the process analytical technology (PAT) initiative of the US Food and Drug Administration (FDA) (Scheper et al. Anal Chim Acta 163:111-118, 1984; Reardon and Scheper 1995; Schügerl et al. Trends Biotechnol 4:11-15, 1986). This contribution gives an overview of non-invasive, image-based, in-situ systems and their applications. The main focus is directed at the wide application area of in-situ microscopes. These inline image analysis systems enable the determination of indirect and direct cell variables in real time without sampling, but also have application potential in crystallization, material analysis, polymer research, and the petrochemical industry.

The adsorption of proteins by a smectitic clay mineral was investigated. The clay used in this study is a mixture of montmorillonite and amorphous SiO(2). Due to the high porosity the montmorillonite units are accessible for protein adsorption. The amorphous silica prevents the montmorillonite from swelling and allows column packing. Protein adsorption was performed at different pH under static conditions. Furthermore, static capacities were determined. The material reveals high adsorption capacities for proteins under static conditions (270-408 mg/g), whereby proteins are mainly adsorbed via electrostatic interactions. The Freundlich isotherm is suggested as an adsorption model. For desorption a pH shift was found to be most effective. Binding and elution of human serum albumin and ovalbumin were tested under dynamic conditions. Dynamic capacities of about 40 mg/g for ovalbumin at 764 cm/h were found. The clay mineral provides suitable properties for the application as cost-efficient, alternative separation material.

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Fracture healing is a complicated process involving many growth factors, cells, and physical forces. In cases, where natural healing is not able, efforts have to be undertaken to improve healing. For this purpose, tissue engineering may be an option. In order to stimulate cells to form a bone tissue several factors are needed: cells, scaffold, and growth factors. Stem cells derived from bone marrow or adipose tissues are the most useful in this regard. The differentiation of the cells can be accelerated using mechanical stimulation. The first part of this chapter describes the influence of longitudinal strain application. The second part uses a sophisticated approach with stem cells on a newly developed biomaterial (Sponceram) in a rotating bed bioreactor with the administration of bone morphogenetic protein-2. It is shown that such an approach is able to produce bone tissue constructs. This may lead to production of larger constructs that can be used in clinical applications.