2022, Henriksson, Anders, Neubauer, Peter, Birkholz, Mario

The performance of receptor-based biosensors is often limited by either diffusion of the analyte causing unreasonable long assay times or a lack of specificity limiting the sensitivity due to the noise of nonspecific binding. Alternating current (AC) electrokinetics and its effect on biosensing is an increasing field of research dedicated to address this issue and can improve mass transfer of the analyte by electrothermal effects, electroosmosis, or dielectrophoresis (DEP). Accordingly, several works have shown improved sensitivity and lowered assay times by order of magnitude thanks to the improved mass transfer with these techniques. To realize high sensitivity in real samples with realistic sample matrix avoiding nonspecific binding is critical and the improved mass transfer should ideally be specific to the target analyte. In this paper we cover recent approaches to combine biosensors with DEP, which is the AC kinetic approach with the highest selectivity. We conclude that while associated with many challenges, for several applications the approach could be beneficial, especially if more work is dedicated to minimizing nonspecific bindings, for which DEP offers interesting perspectives.

2018, Glogener, Paul, Krause, Michael, Katzer, Jens, Schubert, Markus A., Birkholz, Mario, Bellmann, Olaf, Kröger-Koch, Claudia, Hammon, Harald M., Metges, Cornelia C., Welsch, Christine, Ruff, Roman, Hoffmann, Klaus P.

A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS) prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.

2020, Abt, Vinzenz, Gringel, Fabian, Han, Arum, Neubauer, Peter, Birkholz, Mario

Microalgae biotechnology has a high potential for sustainable bioproduction of diverse highvalue biomolecules. Some of the main bottlenecks in cell-based bioproduction, and more specifically in microalgae-based bioproduction, are due to insufficient methods for rapid and efficient cell characterization, which contributes to having only a few industrially established microalgal species in commercial use. Dielectrophoresis-based microfluidic devices have been long established as promising tools for label-free handling, characterization, and separation of broad ranges of cells. The technique is based on differences in dielectric properties and sizes, which results in different degrees of cell movement under an applied inhomogeneous electrical field. The method has also earned interest for separating microalgae based on their intrinsic properties, since their dielectric properties may significantly change during bioproduction, in particular for lipid-producing species. Here, we provide a comprehensive review of dielectrophoresis-based microfluidic devices that are used for handling, characterization, and separation of microalgae. Additionally, we provide a perspective on related areas of research in cell-based bioproduction that can benefit from dielectrophoresis-based microdevices. This work provides key information that will be useful for microalgae researchers to decide whether dielectrophoresis and which method is most suitable for their particular application. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

2020, Henriksson, Anders, Kasper, Laura, Jäger, Matthias, Neubauer, Peter, Birkholz, Mario

The combination of extreme miniaturization with a high sensitivity and the potential to be integrated in an array form on a chip has made silicon-based photonic microring resonators a very attractive research topic. As biosensors are approaching the nanoscale, analyte mass transfer and bonding kinetics have been ascribed as crucial factors that limit their performance. One solution may be a system that applies dielectrophoretic forces, in addition to microfluidics, to overcome the diffusion limits of conventional biosensors. Dielectrophoresis, which involves the migration of polarized dielectric particles in a non-uniform alternating electric field, has previously been successfully applied to achieve a 1000-fold improved detection efficiency in nanopore sensing and may significantly increase the sensitivity in microring resonator biosensing. In the current work, we designed microring resonators with integrated electrodes next to the sensor surface that may be used to explore the effect of dielectrophoresis. The chip design, including two different electrode configurations, electric field gradient simulations, and the fabrication process flow of a dielectrohoresis-enhanced microring resonator-based sensor, is presented in this paper. Finite element method (FEM) simulations calculated for both electrode configurations revealed ?E2 values above 1017 V2m-3 around the sensing areas. This is comparable to electric field gradients previously reported for successful interactions with larger molecules, such as proteins and antibodies. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

2017, Theuer, Lorenz, Lehmann, Micha, Junne, Stefan, Neubauer, Peter, Birkholz, Mario

An affinity-viscometry-based micro-sensor probe for continuous glucose monitoring was investigated with respect to its suitability for bioprocesses. The sensor operates with glucose and dextran competing as binding partner for concanavalin A, while the viscosity of the assay scales with glucose concentration. Changes in viscosity are determined with a micro-electromechanical system (MEMS) in the measurement cavity of the sensor probe. The study aimed to elucidate the interactions between the assay and a typical phosphate buffered bacterial cultivation medium. It turned out that contact with the medium resulted in a significant long-lasting drift of the assay’s viscosity at zero glucose concentration. Adding glucose to the medium lowers the drift by a factor of eight. The cglc values measured off-line with the glucose sensor for monitoring of a bacterial cultivation were similar to the measurements with an enzymatic assay with a difference of less than ±0.15 g·L−1. We propose that lectin agglomeration, the electro-viscous effect, and constitutional changes of concanavalin A due to exchanges of the incorporated metal ions may account for the observed viscosity increase. The study has demonstrated the potential of the MEMS sensor to determine sensitive viscosity changes within very small sample volumes, which could be of interest for various biotechnological applications.