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Implantable Nanotube Sensor Platform for Rapid Analyte Detection.

ABSTRACT: The use of nanoparticles within living systems is a growing field, but the long-term effects of introducing nanoparticles to a biological system are unknown. If nanoparticles remain localized after in vivo implantation unanticipated side effects due to unknown biodistribution can be avoided. Unfortunately, stabilization and retention of nanoparticles frequently alters their function.[1] In this work multiple hydrogel platforms are developed to look at long-term localization of nanoparticle sensors with the goal of developing a sensor platform that will stabilize and localize the nanoparticles without altering their function. Two different hydrogel platforms are presented, one with a liquid core of sensors and another with sensors decorating the hydrogel's exterior, that are capable of localizing the nanoparticles without inhibiting their function. With the use of these new hydrogel platforms nanoparticle sensors can be easily implanted in vivo and utilized without concerns of nanoparticle impact on the animal.

SUBMITTER: Hofferber EM

PROVIDER: S-EPMC6827871 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Implantable Nanotube Sensor Platform for Rapid Analyte Detection.

Hofferber Eric Michael EM Stapleton Joseph Anthony JA Adams Janelle J Kuss Mitchell M Duan Bin B Iverson Nicole Marie NM

Macromolecular bioscience 20190403 6

The use of nanoparticles within living systems is a growing field, but the long-term effects of introducing nanoparticles to a biological system are unknown. If nanoparticles remain localized after in vivo implantation unanticipated side effects due to unknown biodistribution can be avoided. Unfortunately, stabilization and retention of nanoparticles frequently alters their function.[1] In this work multiple hydrogel platforms are developed to look at long-term localization of nanoparticle senso ...[more]

PMID: 30942955

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Project description:BackgroundRapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT) for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs). As proof of principle, we use oriented immobilization of pyruvate kinase (PK) and luciferase (Luc) on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE), a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices.Methods and findingsWe performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815) with the current gold standard for biomarker detection, ELISA-with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA.ConclusionsOriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using oriented immobilization of active enzymes on NPs as the basis for a highly rapid and sensitive biomarker detection platform. This addresses a key challenge in developing a PoCT platform for time sensitive and difficult to diagnose pathologies.

Dataset Information

Implantable Nanotube Sensor Platform for Rapid Analyte Detection.

Publications

Implantable Nanotube Sensor Platform for Rapid Analyte Detection.

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