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Boris Mizaikoff and Christine Kranz – on the way to systems analytics

The two chemists Boris Mizaikoff and Christine Kranz have a great deal in common: they are married to each other, they have children together and they work at the same university on projects that combine technologies and methods to create “multifunctional analytical platforms” at the Department of Analytical and Bioanalytical Chemistry at Ulm University.

The two researchers are working on combining different technologies in systems analytics, a chemical approach that has its biological counterpart in systems biology. However, this approach is not yet firmly established as part of the natural sciences. Although there are many analytical methods available – both invasive and non-invasive – for analysing biological samples, they are usually used sequentially rather than simultaneously.

The couple complement each other in their research field

Researcher couple Dr. Christine Kranz and Prof. Dr. Boris Mizaikoff © Pytlik
Whenever one talks of Boris Mizaikoff, his life and research partner Christine Kranz is inevitably part of the reference. Mizaikoff studied chemical engineering at the Technical University in Vienna, before transferring to analytical chemistry during his doctorate and doing his habilitation in the same field before going on to spend some time doing research in Austin, Texas. Mizaikoff is now focussed on optical and chemical sensor technology, moving slightly away from analytical chemistry in order to concentrate on the development of new technologies and new analytical methods.

After his habilitation, Mizaikoff accepted a post at the Georgia Institute of Technology in Atlanta at the same time as his wife was about to finish her postdoctoral period. As Mizaikoff says, this gave the two scientists a 'two-body problem', referring to the situation of couples where both partners work in academics. His wife also wished to continue her scientific career, and was actually offered a position as a research scientist.

Work-family conflict impacts career goals

While she was doing her doctorate at the Department of General Chemistry and Biochemistry at the Technical University in Munich, which is a leader in the development of amperometric biosensors, Christine Kranz developed an electrochemical scanning probe microscope. She applied for a DFG research grant which would have enabled her to do a postdoctoral period in the USA, but decided against this as she was then pregnant with twins. The new family situation had an impact on the researchers’ career goals – her husband Boris Mizaikoff moved to the USA alone.

Intercontinental cooperation

Amperometric ATP microsensor, based on a dual electrode for the measurement of ATP involving live preparations of glomus caroticum. © Mizaikoff/Kranz, cooperation: Dr. E. Gauda, Johns Hopkins Hospital, Baltimore
After one and a half years childcare leave, Kranz then continued her postdoctoral studies at the Technical University of Vienna. Her new research group focused on atomic force microscopy, and Kranz succeeded in integrating atomic force and electrochemical microscopy and in filing a few patents. She also intensified the scientific cooperation with her husband at Georgia Tech, where she was eventually offered a position.

In the College of Science at Georgia Tech, which is actually a classical engineering school, Mizaikoff and Kranz established the Applied Sensors Laboratory (ASL) at the School of Chemistry and Biochemistry. The two researchers spent eight years working on complex life science issues with a particular focus on biology and physiology, two fields that were growing in importance at the time both in the USA and around the world. Funded with grants from the National Institutes of Health, they developed new analytical methods in cooperation with external partners.

The couple move to Ulm

Mizaikoff and Kranz moved to Ulm in June 2008 to accept positions - Mizaikoff as professor and Kranz as scientist - in the Department of Analytics and continue their joint work which is part of the University’s life science research priority.

Combining technologies works well for the life sciences

Combination of scanning electrochemical microscopy (SECM) and atomic force microscopy (AFM) by integrating micro- and nanoelectrodes in atomic microscopy tips. The schematic shows a cross section through a combined AFM-SECM tip (not to scale) with an integrated amperometric glucose sensor (the enzyme glucose oxidase was immobilised at the integrated nanoelectrode) for the localised detection of glucose. Topographic (top left) and electrochemical (top right) information that is obtained at the same time is shown with symbols.
Combination of scanning electrochemical microscopy (SECM) and atomic force microscopy (AFM) by integrating micro- and nanoelectrodes in atomic microscopy tips. The schematic shows a cross section through a combined AFM-SECM tip (not to scale) with an inte
The innovative combination of atomic force with electrochemical microscopy combines topographic investigation with the measurement of electroactivity. According to Kranz, the combination is excellently suited to life science applications because many biomolecules are redox active. However, the technology is also suitable for corrosion research, the investigation of polymer-coated surfaces and for the analysis of fundamental processes in the development of fuel cells.

Complementary research

Mizaikoff’s major research area complements Christine Kranz’s work. Mizaikoff focuses on optical spectroscopy and sensor technology. For the last 15 years, he has concentrated on miniaturising the classical oscillation spectroscopy of relatively big laboratory devices and turning them into compact sensor platforms. The small devices have the advantage of being able to analyse the optical characteristics of molecules in the long-wave spectral area (middle infrared: 3-20 µm), where molecules start to oscillate and rotate. This gives any (bio) molecules a molecular-specific sequence of oscillation bands, which serves to identify and quantify the molecule under investigation.

Miniaturisation for biological samples

Previously, this method had mainly been used for larger sample volumes in the gas and liquid phase because relatively large IR spectrometers were used. The two researchers are now trying to adapt this technology to smaller biological samples (smaller in both volume and size; in vitro and in vivo as catheters). Working with hospital doctors, the researchers are hoping to also use this miniaturised technology for the analysis of breathing gas.

Expansion of platform with optics and spectroscopy

Schematic representation of a systems analytical combination platform delivering synchronised topographic, electrochemical and spectroscopic information of biological systems. (Photo: Mizaikoff/Kranz)
Schematic representation of a systems analytical combination platform delivering synchronised topographic, electrochemical and spectroscopic information of biological systems. © Mizaikoff/Kranz
Their “multifunctional analytical platform” has come together over the last few years. The combination of atomic force microscopy and electrochemistry, which delivers chemical and topographic parameters simultaneously (rather than sequentially), will now be combined with optics and spectroscopy. What is the advantage of this combined package? Three different or multiple parameters can be measured in a time- and site-correlated way, which makes it the ideal technology to use on continuously changing, dynamic biological systems.

Kranz and Mizaikoff will most likely spend the next 15 years on the further development of this combination technology in order to make it suitable for cell physiological applications, clinical and medical applications or even for medical analytics.

Multiparameter measurements provide direct access to molecules

Today, the systems can already be used for the detection of disease-related molecular alterations on cells or tissue systems with spatial and temporal resolution. The current most common system for this is confocal fluorescence microscopy, which has the disadvantage of requiring an optical marker to visualise the species or molecule under investigation. Kranz and Mizaikoff hope that their multiparametric measurements will give them direct access to molecules and molecular processes.

How small can a biosensor be?

Christine Kranz (47). (Photo: Pytlik)
Kranz assumes that the smallest detectable measurement point is 100nm (subcellular dimension), which enables the laterally resolved analysis of an individual cell. The combination technology can also be used for larger dimensions in the case of cell assemblies or tissue segments. Kranz and Mizaikoff’s basic research involves assessing the size of biosensors: how small can a biosensor be in order to reliably detect small concentrations of molecules? The further miniaturisation will take another few years before routine application is possible. However, the two researchers can well imagine their technology platform being commercially available within a few years. This would give clinicians and researchers access to a device that could easily be modified for use with user-specific electrodes or integrated light wave guides.

The two chemists are currently working on combining three things - atomic force, electrochemical microscopy and IR spectroscopy. Combined atomic force electrochemical microscopy has existed since 2000 and about five to six groups worldwide are currently working on this technology.

Better measurement of complex biological systems

Boris Mizaikoff (43) (Photo: Pytlik)
Complementary to the systems biology approach, the two Ulm University researchers hope to establish systems analytics which will allow them to measure selected biological processes in a time- and site-resolved way. The goal is to replace model assumptions through quantitative measurements on real cells: “We hope to obtain the figures that are required for systems biology libraries and the simulations,” said Mizaikoff.

Kranz and Mizaikoff can still look forward to finding many different combinations. One possibility might be the integration of confocal fluorescence microscopy or mass spectroscopy. The researchers have already considered various technological approaches and hope to submit funding proposals.

Application potential for the pharmaceutical industry

Kranz and Mizaikoff’s systems analytical approach can also be used in the pharmaceutical industry, in the drug discovery process and in drug screening because the combination of different methods enables the researchers to study the interaction of target molecules with cells on the cell surface.

Kranz and Mizaikoff also have plans to introduce the interdisciplinary approach which they practised in the USA, i.e. the combination of natural sciences, engineering sciences, medicine and biology. They have high hopes for the cooperation with medical researchers in Ulm, but they have also made initial contact with additional academic partners on the Ulm University campus and are working closely with regional industry partners.

Establishment of nanomedicine at Ulm University

Over the next five years, the two researchers hope to establish nanomedicine research at the University of Ulm and advance interdisciplinary projects with researchers working in the fields of medicine, natural sciences and the engineering sciences. In addition, the two researchers also hope to focus on more exotic topics, such as deep sea analytics. As open and flexible as the two researchers are, they can also envisage setting up collaborative projects with technology-oriented small- and medium-sized companies in Baden-Württemberg.

In the meantime, they are hoping to increase their research group to 20 people, consisting of two interdisciplinary teams per research area. Luck has been with Mizaikoff and Kranz in Ulm and they have been able to achieve the difficult balance of combining family and professional life to the best advantage of both themselves and their children.

Walter Pytlik - 11 November 2008
© BIOPRO Baden-Württemberg GmbH
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