Existing gastrointestinal(GI)diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus.In the GI tract,local inflammatory processes induce alterations in tight...Existing gastrointestinal(GI)diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus.In the GI tract,local inflammatory processes induce alterations in tight junction proteins,enhancing paracellular ion permeability.Although transepithelial electrical resistance(TEER)may be used in the laboratory to assess mucosal barrier integrity,there are no existing methodologies for characterizing tight junction dilation in vivo.Addressing this technology gap,intraluminal bioimpedance sensing may be employed as a localized,non-invasive surrogate to TEER electrodes used in cell cultures.Thus far,bioimpedance has only been implemented in esophagogastroduodenoscopy(EGD)due to the need for external electronics connections.In this work,we develop a novel,noise-resilient Bluetooth-enabled ingestible device for the continuous,non-invasive measurement of intestinal mucosal“leakiness.”As a proof-of-concept,we validate wireless impedance readout on excised porcine tissues in motion.Through an animal study,we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure.Device measurements are validated using standard benchtop methods for assessing mucosal permeability.展开更多
Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal(GI)disease.As device complexity increases,so too does the demand for more effe...Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal(GI)disease.As device complexity increases,so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations.While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions,their application is limited due to the geometric restrictions imposed by standard coating methods.Dip,pan,and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment.However,some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery.To this end,we present the freestanding region-responsive bilayer(FRRB),a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components.The bilayer is composed of rigid polyethylene glycol(PEG)under a flexible pH-responsive Eudragit®FL 30 D 55,which protects the contents of the capsule until it arrives in the targeted intestinal environment.The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms,some of which are demonstrated here.In this paper,we characterize and validate the use of this technology in a simulated intestinal environment,confirming that the FRRB can be tuned for small intestinal release.We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.展开更多
基金supported by the National Science Foundation ECCS program,award#1939236NCS program,award#1926793。
文摘Existing gastrointestinal(GI)diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus.In the GI tract,local inflammatory processes induce alterations in tight junction proteins,enhancing paracellular ion permeability.Although transepithelial electrical resistance(TEER)may be used in the laboratory to assess mucosal barrier integrity,there are no existing methodologies for characterizing tight junction dilation in vivo.Addressing this technology gap,intraluminal bioimpedance sensing may be employed as a localized,non-invasive surrogate to TEER electrodes used in cell cultures.Thus far,bioimpedance has only been implemented in esophagogastroduodenoscopy(EGD)due to the need for external electronics connections.In this work,we develop a novel,noise-resilient Bluetooth-enabled ingestible device for the continuous,non-invasive measurement of intestinal mucosal“leakiness.”As a proof-of-concept,we validate wireless impedance readout on excised porcine tissues in motion.Through an animal study,we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure.Device measurements are validated using standard benchtop methods for assessing mucosal permeability.
基金This work was supported by the National Science Foundation NCS Program under Award#5234852.The authors acknowledge support from the Clark Doctoral Fellows Program,TerrapinWorks,the University of Maryland NanoCenter and its FabLab.
文摘Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal(GI)disease.As device complexity increases,so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations.While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions,their application is limited due to the geometric restrictions imposed by standard coating methods.Dip,pan,and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment.However,some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery.To this end,we present the freestanding region-responsive bilayer(FRRB),a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components.The bilayer is composed of rigid polyethylene glycol(PEG)under a flexible pH-responsive Eudragit®FL 30 D 55,which protects the contents of the capsule until it arrives in the targeted intestinal environment.The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms,some of which are demonstrated here.In this paper,we characterize and validate the use of this technology in a simulated intestinal environment,confirming that the FRRB can be tuned for small intestinal release.We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.
