The Belder Group's research focuses on lab-on-a-chip technology as a fundamental science in chemistry. A broad field of research and application of lab-on-a-chip technology is carried out in the Belder laboratories at the University of Leipzig. The Belder group is known for miniaturized separation techniques such as chip electrophoresis and chip HPLC.

enlarge the image: Vergrößerte Aufnahme eines Mikrofluidik Chips
Mikrofluidik Chip, Foto: Universität Leipzig, AK Konzentrationsanalytik

The Belder Group is known for miniaturized separation techniques such as chip electrophoresis and chip HPLC. The Belder lab also works on detection techniques such as coupling microfluidic chips with mass spectrometry or ion mobility spectrometry, and optical techniques such as fluorescence and Raman microscopy. A particular focus in recent years has been on integrated chip laboratories, which combine chemical reactors and analysis units on a single chip.

Our research topics

enlarge the image: Modular microfluidic system created using SLE technology, Figure: Uni Leipzig, AG Belder
Modular microfluidic system created using SLE technology, Figure: Uni Leipzig, AG Belder

In the research area of modular microfluidic systems, monolithic components are fabricated from fused-silica glass using selective laser-induced etching (SLE). SLE technology provides access to unique three-dimensional structures that are not possible with conventional photolithographic methods. The individual monolithic chip components are individually combined into application-specific microfluidic systems and used in cutting-edge research projects such as segmented flow reaction monitoring and miniaturized HPLC separation technology.

Supervising PhD student(s)

M.Sc. Matthias Polack

M.Sc. Matthias Polack

Ph.D. Student

enlarge the image: HPLC chip with scintillation detector for the detection of tritium compounds, Figure: Uni Leipzig, AG Belder
HPLC chip with scintillation detector for the detection of tritium compounds, Figure: Uni Leipzig, AG Belder

Tritium refers to the naturally occurring radioactive isotope of hydrogen. Due to the low energy of the electron produced during β-decay and the comparatively short half-life, tritium is used as a preferred labeling substance.

Within the framework of the Research Training Group GRK 2721 "Hydrogen Isotopes 123H" (Project ID 443871192), funded by the German Research Foundation (DFG), the miniaturization of scintillation measurement for the detection of tritium compounds is investigated. The main goals are reducing the amounts of radioactive substances and toxic scintillation fluids, handling them safely, and coupling the analysis platform to microreactors and chip HPLC systems.

Supervising PhD student(s)

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M.Sc. Jantje Pauline Bäcker

Ph.D. Student

Linnéstraße 3, Room 220
04103 Leipzig

Telephone: +49 341 97-36103

enlarge the image: Coupling of miniaturized chip systems with ion mobility spectrometry (IMS) for fast 2D separation, Figure: Uni Leipzig, AG Belder.
Coupling of miniaturized chip systems with ion mobility spectrometry (IMS) for fast 2D separation, Figure: Uni Leipzig, AG Belder.

In this project, the coupling of miniaturized chip systems with ion mobility spectrometry (IMS) is developed. The low instrumental complexity of such IMS devices leads to compact, robust and fast detection, which even allows discrimination between isobars. The current focus is on the combination with upstream on-chip separation techniques to enable two-dimensional separations of samples in the seconds to minutes range. In addition, IMS is being investigated for detection of ultra-fast droplet microfluidics.

Supervising PhD student(s)

M.Sc. Klaus Welters

M.Sc. Klaus Welters

Ph.D. Student

Linnéstraße 3, Room 223
04103 Leipzig

Telephone: +49 341 97-36068

enlarge the image: Double emulsion droplets as small reaction vessels for the investigation of reactions at phase interfaces, Figure: Uni Leipzig, AG Belder
Double emulsion droplets as small reaction vessels for the investigation of reactions at phase interfaces, Figure: Uni Leipzig, AG Belder

This project deals with the microfluidic generation of double emulsion droplets ("emulsion of an emulsion" or "a droplet within a droplet"). Double emulsion droplets are emulsion systems consisting of three immiscible liquid phases (usually oils and water) whose interfaces are stabilized by surfactants. We want to use double emulsion droplets as small reaction compartments to study reactions at the oil-water interface (e.g., complexation reactions or enzyme-catalyzed reactions). In addition, we intend to couple the double emulsion droplets with ESI mass spectrometry as the detection technique of choice to monitor the reaction outcome.

Supervising PhD Student(s)

enlarge the image: Regeneration of surfaces for non-destructive, sensitive SERS detection, Figure: Uni Leipzig, AG Belder
Regeneration of surfaces for non-destructive, sensitive SERS detection, Figure: Uni Leipzig, AG Belder

Compared to classical Raman spectroscopy, surface enhanced Raman spectroscopy (SERS) allows signal intensities that are increased by a factor of up to 109, which enables the non-destructive detection of single molecules. Often, nanostructured surfaces can only be used once, because adsorption effects interfere with the detection of subsequent analytes. We have succeeded in making the commonly used silver and gold surfaces usable again by electrical contacting, which should enable the integration of surface-enhanced Raman spectroscopy into on-line techniques such as HPLC.

Supervising PhD Student(s)

M.Sc. Maximilian Blaha

M.Sc. Maximilian Blaha

Ph.D. Student

Linnéstraße 3, Room 222
04103 Leipzig

Telephone: +49 341 97-36088

enlarge the image: Chip-HPLC-MS coupling for the investigation of heterogeneously catalyzed synthesis processes, Figure: Uni Leipzig, AG Belder
Chip-HPLC-MS coupling for the investigation of heterogeneously catalyzed synthesis processes, Figure: Uni Leipzig, AG Belder

In this project, microreactors are used to study heterogeneously catalyzed synthesis processes in flow-through. For characterization, the particle-packed reactors used for this purpose are directly coupled with (chip)-HPLC-MS and controlled via fluidic circuits. Such integrated systems offer various possibilities for automation, throughput increase as well as reactor control and can thus be used for a resource-saving screening of optimal catalyst and reaction conditions.

Supervising PhD Student(s)

M.Sc. Hannes Westphal

M.Sc. Hannes Westphal

Ph.D. Student

Linnéstraße 3, Room 225
04103 Leipzig

Telephone: +49 341 97-36066

enlarge the image: Microfluidic system for the generation of small reaction compartments on a p/n-scale and detection of the reaction products by spectroscopic/mass spectrometric detection, Figure: Uni Leipzig, AG Belder.
Microfluidic system for the generation of small reaction compartments on a p/n-scale and detection of the reaction products by spectroscopic/mass spectrometric detection, Figure: Uni Leipzig, AG Belder.

In this topic area, immiscible phases are brought together in a microfluidic channel to form droplets on the pico- to nanolitre scale. These can be used as the smallest reaction vessels for chemical and biochemical transformations and can be freely manipulated. Using Raman spectroscopy, fluorescence spectroscopy as well as mass spectrometry as analytical tools, individual catalytic species can be observed and characterized.

Supervising PhD Student(s)

M.Sc. Marie van der Loh

M.Sc. Marie van der Loh

Ph.D. Student

Linnéstraße 3, Room 216
04103 Leipzig

Telephone: +49 341 97-36106

enlarge the image: Coupling of high temperature chipHPLC and chipSFC with mass spectrometric detector, Figure: Uni Leipzig, AG Belder
Coupling of high temperature chipHPLC and chipSFC with mass spectrometric detector, Figure: Uni Leipzig, AG Belder

In addition to the chip-HPLC methologies developed in the working group as well as the coupling with mass spectrometry, the development of new microfluidic SFC systems (supercritical fluid chromatography) represents a promising further improvement. The use of supercritical fluids such as sCO2 and their complete miscibility with organic modifiers such as methanol allows the combination of normal and reversed phase systems in a single chip platform. Low viscosities and high diffusion coefficients enable exceptionally short separation times of a few seconds, and the "waste product" CO2 proves to be an environmentally friendly and safe alternative to toxic solvents.
The current technological challenges lie in the controlled handling of highly compressible liquids in confined spaces, the development of pressure stable miniaturised instrumentation and the sophisticated coupling with alternative detection techniques such as ion mobility spectrometry.

Supervising PhD Student(s)

M.Sc. Chris Weise

M.Sc. Chris Weise

Ph.D. Student

Linnéstraße 3, Room 220
04103 Leipzig

Telephone: +49 341 97-36103

M.Sc. Julius Schwieger

M.Sc. Julius Schwieger

Ph.D. Student

Linnéstraße 3, Room 223
04103 Leipzig

Telephone: +49 341 97-36068

enlarge the image: Coupling of a digital microfluidic chip with surface-enhanced Raman spectroscopy for automated execution of chemical syntheses / monitoring of the reaction process, Figure: Uni Leipzig, AG Belder.
Coupling of a digital microfluidic chip with surface-enhanced Raman spectroscopy for automated execution of chemical syntheses / monitoring of the reaction process, Figure: Uni Leipzig, AG Belder.

The focus of this research is on the development and automation of lab-on-a-chip technologies for analytical chemistry applications. This is achieved through a relatively new paradigm of microfluidics, digital microfluidics (DMF). A DMF chip contains arrays of patterned metal electrodes fabricated by PVD, photolithography, and wet chemical etching. This allows discrete droplets ranging in size from nano- to microliters to be moved, e.g., dispersed, transported, divided, and combined, by selectively applying electrical potentials to the individual electrodes. This enables automated execution of chemical syntheses and monitoring of the reaction progress by coupling with various detection methods such as surface-enhanced Raman spectroscopy or mass spectroscopy monitoring.

Supervising PhD Student(s)

M.Eng. Anish Das

M.Eng. Anish Das

Ph.D. Student

Linnéstraße 3, Room 223
04103 Leipzig

Telephone: +49 341 97-36068

Third-party funded large-scale equipment since 2018

Thanks to an infrastructure measure funded by the Free State of Saxony, a novel tuneable quantum cascade laser IR microscope will be made available to the Belder working group in 2021. The use of this QCL-IR microscope is expected to enable for the first time IR-based label-free, real-time chemical imaging of dynamic processes in microfluidic IR-transparent microfluidic chips.

enlarge the image:
Quantum Cascade Laser IR Microscope, Foto: Universität Leipzig, AK Konzentrationsanalytik

Aims of the project

Current scientific activities include the microfluidic chip / QCL-IR microscope setup as well as microsynthetic research for the first label-free, real-time IR tracking of chemical processes in chip-based microsystems. For this purpose, organocatalytic model reactions from the research group FOR 2177 are initially investigated, supported by our coorperation partners from the synthetic chemistry working groups. Among the most important aspects of this research are the development of chip designs such as microflow reactors and the 3D microfabrication of the corresponding chips in IR-transparent materials using SLE technology. This synergistic interplay of the two cutting-edge technologies SLE and quantum cascade laser IR microscopy is currently unique, opening up completely new possibilities and, in the long term, a significant innovation boost for basic research in micro-chemistry.

As part of an ERDF infrastructure measure, the instrumental infrastructure of the university will be strengthened and the AK Belder will be enabled to use a high-speed triple quadrupole mass spectrometer. This instrument can detect multiple target analytes over a wide range of masses and concentrations with unsurpassed speed and sensitivity. Triple quadrupole mass spectrometry is therefore the undisputed method of choice today in application fields where high speed and excellent detection limits are equally decisive criteria.

enlarge the image: High-Sensitive High-speed Mass Spectrometer, Image: Agilent
High-Sensitive High-speed Mass Spectrometer, Image: Agilent

Aims of the project

With the financed instrumental upgrade, an ideal basic technical prerequisite has been created to perform mass spectrometric analyses in microsystems with previously unattained sensitivity and speed. Thus, multiple target analytes will now be detected and analyzed simultaneously with unsurpassed speed and sensitivity. The use of the funded instrument in combination with the microlaboratories developed to date now offers the possibility of a real breakthrough for research in the field of single-cell and single-particle catalysis as well as ultrafast chip chromatography.

Within the scope of this ERDF infrastructure measure, a novel 3D laser structuring system based on the selective laser etching (SLE) process is being established. This is a hybrid technique consisting of pre-structuring by an ultrashort pulse laser, in which the layout designed in CAD is transferred to the glass substrate. The laser-treated material has a significantly increased etch rate, so that etching (e.g. with KOH) is favored at these points. This makes it possible to produce complex 3D structures in glass, as shown in the following figure.

enlarge the image: Fotocollage eines Laserstrukturierungssystems zur Erzeugung von Mikro- und Nanostrukturen in Glas und Polymeren (LasMino).
Laserstrukturierungssystem zur Erzeugung von Mikro- und Nanostrukturen in Glas und Polymeren (LasMino). Fotocollage: Universität Leipzig, AK Konzentrationsanalytik

Aims of the project

The 3D laser structuring system is intended to expand the technical-instrumental infrastructure at the Leipzig academic site in the field of chip clean room process technology for microfluidic lab-on-chip systems. The novel process for micro-nano-laser structuring of glass and polymers will be used in all current research areas around the topic of complex, integrated micro-laboratories to overcome current technical limitations and to open up new research and development opportunities, e.g. for coordinated programs like the DFG research group "InChem". This includes research topics such as the development of optically fully transparent microcavity electrode arrays for tissue-based drug testing or the miniaturization and seamless integration of chemical flow synthesis, analytical separation techniques and high-performance detection methods in complex microlaboratories.

As part of an infrastructure measure funded by the German Research Foundation (DFG) and the Free State of Saxony, a laser spectroscopy microscope for studying chemical processes in chip-based microlaboratories was procured in 2019 and installed in the laboratory facilities of the Belder working group at the University of Leipzig. This system features a custom-built dual-microscope setup, multiple laser excitation sources including a tuneable TiSa laser, and a wide variety of options for sensitive detection. The versatility of the equipment setup now available enables simultaneous detection of chemical species at different locations on a chip by fluorescence and Raman spectroscopic methods, allowing significant advances in the research and development of miniaturized analytical and synthesis platforms to be realized.

enlarge the image: Photo of a Fluorescence / Raman microscope for the development of miniaturized analysis and synthesis platforms. Photo: University of Leipzig, AK Concentration Analytics
Fluorescence / Raman microscope for the development of miniaturized analysis and synthesis platforms. Photo: University of Leipzig, AK Concentration Analytics

Aims of the project

In addition to the sensitive and selective analysis of diverse species, processes and materials will also be studied and visualized in more detail at the micrometer scale. The system opens up previously unavailable opportunities for research and development of miniaturized analytical systems of high complexity and functionality. Furthermore, the dual microscope will be used across faculties for research on a wide variety of microspectroscopy topics. In addition to intensive research activities, the system will also be used in advanced teaching in the master's degree program in chemistry, providing scientific staff and students with novel opportunities in spectroscopic analysis.

Large equipment before 2018

Of the large-scale equipment acquired prior to 2018, the following are being used in current research projects:

  • Various mass spectrometers
  • An ion mobility spectrometer
  • A time-resolved fluorescence microscope
  • One Raman microscope

Vacancies

At the Institute of Analytical Chemistry of the University of Leipzig in the professorship Concentration Analytics we offer temporary positions within the framework of externally funded projects.
In addition to the supervision of doctoral theses, bachelor, advanced or master theses on various topics are offered in our working group.

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