In vitro quantification of botulinum neurotoxin type A1 using immobilized nerve cell-mimicking nanoreactors in a microfluidic platform

The bacterial toxin botulinum neurotoxin A (BoNT/A) is not only an extremely toxic substance but also a potent pharmaceutical compound that is used in a wide spectrum of neurological disorders and cosmetic applications. The quantification of the toxin is extremely challenging due to its extraordinar...

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Bibliographic Details
Published in:Analyst (London) 2019-09, Vol.144 (19), p.5755-5765
Main Authors: Weingart, Oliver G, Eyer, Klaus, Lüchtenborg, Christian, Sachsenheimer, Timo, Brügger, Britta, van Oostrum, Marc, Wollscheid, Bernd, Dittrich, Petra S, Loessner, Martin J
Format: Article
Language:English
Subjects:
Animals
Biocompatibility
Biomimetic Materials
Biosensing Techniques
Botulinum Toxins, Type A - analysis
Catalysis
Catalytic activity
Cells, Immobilized
Drugs, Chinese Herbal - chemistry
Ethics
In vitro methods and tests
In Vitro Techniques - methods
In vivo methods and tests
Lab-On-A-Chip Devices
Liposomes - chemistry
Microfluidic Analytical Techniques - instrumentation
Microfluidic Analytical Techniques - methods
Microfluidic devices
Nanostructures
Neurological diseases
Neurons
Pharmaceuticals
Protein Binding
Serum Albumin, Human - chemistry
Surface Plasmon Resonance
Swine
Toxins
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Summary:The bacterial toxin botulinum neurotoxin A (BoNT/A) is not only an extremely toxic substance but also a potent pharmaceutical compound that is used in a wide spectrum of neurological disorders and cosmetic applications. The quantification of the toxin is extremely challenging due to its extraordinary high physiological potency and is further complicated by the toxin's three key functionalities that are necessary for its activity: receptor binding, internalization-translocation, and catalytic activity. So far, the industrial standard to measure the active toxin has been the mouse bioassay (MBA) that is considered today as outdated due to ethical issues. Therefore, recent introductions of cell-based assays were highly anticipated; their impact however remains limited due to their labor-intensive implementation. This report describes a new in vitro approach that combines a nanosensor based on the use of nerve cell-mimicking nanoreactors (NMN) with microfluidic technology. The nanosensor was able to measure all three key functionalities, and therefore suitable to quantify the amount of physiologically active BoNT/A. The integration of such a sensor in a microfluidic device allowed the detection and quantification of BoNT/A amounts in a much shorter time than the MBA (
ISSN:0003-2654
1364-5528
DOI:10.1039/c9an00817a