TY - JOUR
T1 - Towards a catheter-based impedimetric sensor for the assessment of intestinal histamine levels in IBS patients
AU - Wackers, Gideon
AU - Putzeys, Tristan
AU - Peeters, Marloes
AU - Van de Cauter, Lori
AU - Cornelis, Peter
AU - Wuebbenhorst, Michael
AU - Tack, Jan
AU - Troost, Freddy
AU - Verhaert, Nicolas
AU - Doll, Theodor
AU - Wagner, Patrick
N1 - Funding Information:
We kindly acknowledge financial support by the Research Foundation Flanders FWO for funding the project G.0B25.14N “Monitoring of gut functions and inflammation processes with biomimetic sensors based on molecularly imprinted polymers”. Tristan Putzeys acknowledges funding by Research Foundation Flanders FWO ( 12Y6919N ). Nicolas Verhaert is partially supported by Research Foundation Flanders FWO ( 1804816 N ). Marloes Peeters is supported by the EPSRC New Investigator Award EP/R029296/1 . Partial co-funding by the German DFG Cluster of excellence 2177 Hearing4All was received through Theodor Doll. The authors also wish to thank Prof. Robert Jan Brummer from the School of Medical Sciences at Örebro University (Sweden) cordially for many stimulating discussions in the starting-up phase of the presented work. Assistance in making the demonstration video by Carlos Henrique Campos and Larissa Kim from the universidade de São Paulo (Brazil) is cordially appreciated, their Professor Jonas Gruber made their internship at KU Leuven possible.
Funding Information:
We kindly acknowledge financial support by the Research Foundation Flanders FWO for funding the project G.0B25.14N ?Monitoring of gut functions and inflammation processes with biomimetic sensors based on molecularly imprinted polymers?. Tristan Putzeys acknowledges funding by Research Foundation Flanders FWO (12Y6919N). Nicolas Verhaert is partially supported by Research Foundation Flanders FWO (1804816 N). Marloes Peeters is supported by the EPSRC New Investigator Award EP/R029296/1. Partial co-funding by the German DFG Cluster of excellence 2177 Hearing4All was received through Theodor Doll. The authors also wish to thank Prof. Robert Jan Brummer from the School of Medical Sciences at ?rebro University (Sweden) cordially for many stimulating discussions in the starting-up phase of the presented work. Assistance in making the demonstration video by Carlos Henrique Campos and Larissa Kim from the universidade de S?o Paulo (Brazil) is cordially appreciated, their Professor Jonas Gruber made their internship at KU Leuven possible.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/6/15
Y1 - 2020/6/15
N2 - In this work, we report on the development of a catheter-based sensor designed for measuring the concentration of histamine in the human duodenum. Certain gut disorders, such as the irritable bowel syndrome (IBS), are associated with elevated levels of intestinal histamine due to chronic immune activation. As it is still impossible to determine histamine concentrations in vivo, a nasointestinal catheter with histamine-sensing capabilities has the potential to become a valuable diagnostic instrument. Regarding the sensing principle, we selected impedance spectroscopy using voltages that are compatible with intra-body applications with molecularly imprinted polymers (MIPs) as recognition elements. MIPs are synthetic receptors that offer the advantages of robustness, high specificity and selectivity for histamine as a target. In this specific case, the MIPs were synthesized from acryclic acid monomers, which guarantees a uniform binding capacity within the pH range of intestinal fluid. We have validated the catheter sensor on human intestinal liquids spiked with histamine in a testing setup that mimics the environment inside the duodenum. The dose-response curves show an analytical range between 5 and 200 nM of histamine, corresponding to physiologically normal conditions while higher concentrations correlate with disease. The key output signal of the sensor is the resistive component of the MIP-functionalized titanium electrodes as derived from the equivalent-circuit modelling of full-range impedance spectra. Future applications could be catheters tailored to cardiovascular, urological, gastrointestinal, and neurovascular applications. This, in combination with the versatility of the MIPs, will make this sensor platform a versatile diagnostic tool.
AB - In this work, we report on the development of a catheter-based sensor designed for measuring the concentration of histamine in the human duodenum. Certain gut disorders, such as the irritable bowel syndrome (IBS), are associated with elevated levels of intestinal histamine due to chronic immune activation. As it is still impossible to determine histamine concentrations in vivo, a nasointestinal catheter with histamine-sensing capabilities has the potential to become a valuable diagnostic instrument. Regarding the sensing principle, we selected impedance spectroscopy using voltages that are compatible with intra-body applications with molecularly imprinted polymers (MIPs) as recognition elements. MIPs are synthetic receptors that offer the advantages of robustness, high specificity and selectivity for histamine as a target. In this specific case, the MIPs were synthesized from acryclic acid monomers, which guarantees a uniform binding capacity within the pH range of intestinal fluid. We have validated the catheter sensor on human intestinal liquids spiked with histamine in a testing setup that mimics the environment inside the duodenum. The dose-response curves show an analytical range between 5 and 200 nM of histamine, corresponding to physiologically normal conditions while higher concentrations correlate with disease. The key output signal of the sensor is the resistive component of the MIP-functionalized titanium electrodes as derived from the equivalent-circuit modelling of full-range impedance spectra. Future applications could be catheters tailored to cardiovascular, urological, gastrointestinal, and neurovascular applications. This, in combination with the versatility of the MIPs, will make this sensor platform a versatile diagnostic tool.
KW - Biomimetic sensors
KW - Impedance spectroscopy
KW - Diagnostic methods
KW - Molecularly imprinted polymers
KW - Irritable bowel syndrome
KW - MOLECULARLY IMPRINTED POLYMERS
KW - IRRITABLE-BOWEL-SYNDROME
KW - CAPSULE ENDOSCOPY
KW - BIOMIMETIC SENSOR
KW - MAST-CELLS
KW - LABEL-FREE
KW - BIOSENSOR
KW - PH
KW - GLUCOSE
KW - MICROSENSORS
U2 - 10.1016/j.bios.2020.112152
DO - 10.1016/j.bios.2020.112152
M3 - Article
C2 - 32275205
SN - 0956-5663
VL - 158
JO - Biosensors & Bioelectronics
JF - Biosensors & Bioelectronics
M1 - 112152
ER -