sensing-barrier-tissue-disruption-with-an-organic-electrochemical

Sensing of Barrier Tissue Disruption with an Organic Electrochemical Transistor

The gastrointestinal tract is an example of barrier tissue that provides a physical barrier against entry of pathogens and toxins, while allowing the ...

Ecole Nationale Superieure des Mines

Ion flow across polarized epithelia is a tightly regulated process. Measurement of the transepithelial resistance is a highly relevant parameter for assessing the function or health of the tissue. Dynamic, electrical measurements of transepithelial ion flow are preferred as they provide the most accurate snapshot of effects of external stimuli. Enteric pathogens such as Salmonella typhimurium are known to disrupt ion flow in gastrointestinal epithelia. Here, for the first time, the use of organic transistors as a powerful potential alternative for front-line, disposable, high-throughput diagnostics of enteric pathogens is demonstrated. The transistors' ability to detect early and subtle changes in transepithelial ion flow is capitalized upon to develop a highly sensitive detector of epithelial integrity. Stable operation of the organic devices under physiological conditions is shown, followed by dynamic, pathogen-specific diagnosis of infection of epithelia. Further, operation of the device is possible in complex matrices, showing particular promise for food and safety applications.

Dynamic Monitoring of Salmonella typhimurium Infection of Polarized Epithelia Using Organic Transistors.

Biological reaction calorimetry, also known as biocalorimetry, has led to extensive applications in monitoring and control of different bioprocesses. A simple real-time estimator for biomass and growth rate was formulated, based on in-line measured metabolic heat flow values. The performance of the estimator was tested in a unique bench-scale calorimeter (BioRC1), improved to a sensitivity range of 8 mW l(-1) in order to facilitate the monitoring of even weakly exothermic biochemical reactions. A proportional-integral feedback control strategy based on these estimators was designed and implemented to control the growth rate of Candida utilis, Kluyveromyces marxianus and Pichia pastoris by regulating an exponential substrate feed. Maintaining a particular specific growth rate throughout a culture is essential for reproducible product quality in industrial bioprocesses and therefore a key sequence for the step from quality by analysis to quality by design. The potential of biocalorimetry as a reliable biomass monitoring tool and as a key part of a robust control strategy for aerobic fed-batch cultures of Crabtree-negative yeast cells in defined growth medium was investigated. Presenting controller errors of less than 4% in the best cases, the approach paves the way for the development of a generally applicable process analytical technology platform for monitoring and control of microbial fed-batch cultures.

Investigation of the potential of biocalorimetry as a process analytical technology (PAT) tool for monitoring and control of Crabtree-negative yeast cultures.

The integration of an organic electrochemical transistor with human barrier tissue cells provides a novel method for assessing toxicology of compounds in vitro. Minute variations in paracellular ionic flux induced by toxic compounds are measured in real time, with unprecedented temporal resolution and extreme sensitivity.

Measurement of barrier tissue integrity with an organic electrochemical transistor.

The gastrointestinal epithelium provides a physical and biochemical barrier to the passage of ions and small molecules; however this barrier may be breached by pathogens and toxins. The effect of individual pathogens/toxins on the intestinal epithelium has been well characterized: they disrupt barrier tissue in a variety of ways, such as by targeting tight junction proteins, or other elements of the junctions between adjacent cells. A variety of methods have been used to characterize disruption in barrier tissue, such as immunofluorescence, permeability assays and electrical measurements of epithelia resistance, but these methods remain time consuming, costly and ill-suited to diagnostics or high throughput toxicology.

Article	Year
Dynamic Monitoring of Salmonella typhimurium Infection of Polarized Epithelia Using Organic Transistors. Advanced healthcare materials\| PubMed ID: 24497469	2014
Investigation of the potential of biocalorimetry as a process analytical technology (PAT) tool for monitoring and control of Crabtree-negative yeast cultures. Applied microbiology and biotechnology\| PubMed ID: 21845386	2012
Measurement of barrier tissue integrity with an organic electrochemical transistor. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 22949380	2012
Validation of the organic electrochemical transistor for in vitro toxicology. Biochimica et biophysica acta\| PubMed ID: 23246813	2013

Adel Hama

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