Flexible Multiplexed In2O3 Nanoribbon Aptamer-Field-Effect Transistors for Biosensing

Abstract

Summary Flexible sensors are essential for advancing implantable and wearable bioelectronics toward monitoring chemical signals within and on the body. Developing biosensors for monitoring multiple neurotransmitters in real time represents a key in vivo application that will increase understanding of information encoded in brain neurochemical fluxes. Here, arrays of devices having multiple In 2 O 3 nanoribbon field-effect transistors (FETs) were fabricated on 1.4-μm-thick polyethylene terephthalate (PET) substrates using shadow mask patterning techniques. Thin PET-FET devices withstood crumpling and bending such that stable transistor performance with high mobility was maintained over >100 bending cycles. Real-time detection of the small-molecule neurotransmitters serotonin and dopamine was achieved by immobilizing recently identified high-affinity nucleic-acid aptamers on individual In 2 O 3 nanoribbon devices. Limits of detection were 10 fM for serotonin and dopamine with detection ranges spanning eight orders of magnitude. Simultaneous sensing of temperature, pH, serotonin, and dopamine enabled integration of physiological and neurochemical data from individual bioelectronic devices.

Implantable aptamer–field-effect transistor neuroprobes for in vivo neurotransmitter monitoring

“…There were significant increases in FET responses 12 min after serotonin addition (see table S1 for statistics), demonstrating that the aptamer-FET neuroprobes detected diffusion-related changes in serotonin levels with respect to time. We previously found that the response times of our aptamer-FET sensors are on the order of seconds ( 21 , 23 ); the 12-min response time here is due to target diffusion over ~0.2 cm in the gelatin/aCSF matrix from the addition location to the recording site.…”

“…To construct biosensors, thiol-terminated DNA aptamers were immobilized onto In 2 O 3 surfaces using (3-aminopropyl)triethoxysilane and 3-maleimidobenzoic acid N- hydroxysuccinimide ester for linking ( Fig. 3E ) ( 21 , 23 ). In vitro serotonin detection was performed in artificial cerebrospinal fluid (aCSF), which mimics the ionic strength and composition of the brain extracellular fluid ( 34 ).…”

“…We developed aptamer-field-effect transistor (FET) biosensors for electronic small-molecule detection under high ionic strength conditions (21)(22)(23). We used nanoscale In 2 O 3 semiconducting films (3 to 4 nm) as an ultrasensitive platform for biosensing.…”

“…Because of the high selectivity of the aptamers we use, aptamer-FET biosensors recognize their specific targets but not structurally similar molecules. We recently reported the real-time and simultaneous detection of serotonin and dopamine using aptamer-FET biosensor arrays, establishing a foundation for multiplexed monitoring of brain neurotransmitters and other targets ( 21 ).…”

Recent Advances in In Vivo Neurochemical Monitoring

“…E-AB sensors were also developed for the detection of DA. Andrews’ group constructed flexible aptamer-field-effect-transistors for DA and 5-HT sensing with a 10 fM LOD [ 150 ]. However, most E-AB sensor work focuses on in vitro development and analysis only using serum or blood samples [ 151 , 152 , 153 ].…”