Implantable Aptamer-Graphene Microtransistors for Real-Time Monitoring of Neurochemical Release in Vivo

Wu, Guangfu; Zhang, Nannan; Matarasso, Avi K.; Heck, Ian; Li, Huijie; Lü, Wei; Phaup, J. Glenn; Schneider, Michael J.; Wu, Yixin; Weng, Zhengyan; Sun, He; Gao, Zan; Zhang, Xincheng; Sandberg, Stefan G.; Parvin, Dilruba; Seaholm, Elena; Islam, Syed K.; Wang, Xueju; Phillips, Paul E. M.; Castro, Daniel C.; Ding, Shinghua; Li, De-Pei; Bruchas, Michael R.; Zhang, Yi

doi:10.1021/acs.nanolett.2c00289

Cited by 26 publications

(35 citation statements)

References 57 publications

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“…56 Previous histological studies have shown that polyimide devices of similar thickness and bending stiffness induce minimal immune responses. 30,40 Note that the width of the probes and FETs can be scaled down in a straightforward manner to 50 μm using photolithography, as we have previously demonstrated using Si as the device substrate. 4 Polyimide is thermally stable and compatible with most microfabrication processes up to 350 °C.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Recently, Zhang and co-workers developed graphene-based aptamer-FET biosensors using our aptamers for dopamine and serotonin sensing. 29,30 To monitor neurotransmitters in vivo, we developed Si-based implantable neuroprobes with miniaturized aptamer-FET biosensors. Probes were either 150 or 50 μm in width and thickness at the tips.…”

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confidence: 99%

“…31,34,43,46,47 Flexible devices with the capability to detect neurotransmitters in real time are necessary to understand chemical neurotransmission, particularly via chronic neural recordings. 4,21,30,35 Along these lines, we recently developed a wearable smartwatch for sweat cortisol sensing using flexible polyimide-based aptamer FETs. 28 We also fabricated In 2 O 3 nanoribbon aptamer-FET biosensor arrays on flexible poly-(ethylene terephthalate) (PET) for the multiplexed detection of serotonin, dopamine, pH, and temperature in real time.…”

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confidence: 99%

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Flexible and Implantable Polyimide Aptamer-Field-Effect Transistor Biosensors

et al. 2022

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Monitoring neurochemical signaling across time scales is critical to understanding how brains encode and store information. Flexible (vs stiff) devices have been shown to improve in vivo monitoring, particularly over longer times, by reducing tissue damage and immunological responses. Here, we report our initial steps toward developing flexible and implantable neuroprobes with aptamer-field-effect transistor (FET) biosensors for neurotransmitter monitoring. A high-throughput process was developed to fabricate thin, flexible polyimide probes using microelectromechanical-system (MEMS) technologies, where 150 flexible probes were fabricated on each 4 in. Si wafer. Probes were 150 μm wide and 7 μm thick with two FETs per tip. The bending stiffness was 1.2 × 10 −11 N•m 2 . Semiconductor thin films (3 nm In 2 O 3 ) were functionalized with DNA aptamers for target recognition, which produces aptamer conformational rearrangements detected via changes in FET conductance. Flexible aptamer-FET neuroprobes detected serotonin at femtomolar concentrations in high-ionic strength artificial cerebrospinal fluid. A straightforward implantation process was developed, where microfabricated Si carrier devices assisted with implantation such that flexible neuroprobes detected physiological relevant serotonin in a tissue-hydrogel brain mimic.

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Section: ■ Results and Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Flexible and Implantable Polyimide Aptamer-Field-Effect Transistor Biosensors

et al. 2022

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“…Any other nanostructures should keep being optimized to meet these standards. In addition, the use of these nanotherapies could be complemented with the administration of nanosensors selective to DA and capable of measuring in real-time and at a cellular scale the variations in the concentrations and release kinetics of the neurotransmitter [ 308 , 309 ]. Thus, the impact of the applied nanostructures on the neurological disease-related processes of the patient could be monitored and, thus, the therapy adapted in a tailored manner with respect to the prognosis of the patient.…”

Section: Perspectives On Nanomedicine-based Therapies For Parkinson’s...mentioning

confidence: 99%

Nanomedicine in the Face of Parkinson’s Disease: From Drug Delivery Systems to Nanozymes

Padilla-Godínez

Ruiz-Ortega

Guerra-Crespo

2022

Cells

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The complexity and overall burden of Parkinson’s disease (PD) require new pharmacological approaches to counteract the symptomatology while reducing the progressive neurodegeneration of affected dopaminergic neurons. Since the pathophysiological signature of PD is characterized by the loss of physiological levels of dopamine (DA) and the misfolding and aggregation of the alpha-synuclein (α-syn) protein, new proposals seek to restore the lost DA and inhibit the progressive damage derived from pathological α-syn and its impact in terms of oxidative stress. In this line, nanomedicine (the medical application of nanotechnology) has achieved significant advances in the development of nanocarriers capable of transporting and delivering basal state DA in a controlled manner in the tissues of interest, as well as highly selective catalytic nanostructures with enzyme-like properties for the elimination of reactive oxygen species (responsible for oxidative stress) and the proteolysis of misfolded proteins. Although some of these proposals remain in their early stages, the deepening of our knowledge concerning the pathological processes of PD and the advances in nanomedicine could endow for the development of potential treatments for this still incurable condition. Therefore, in this paper, we offer: (i) a brief summary of the most recent findings concerning the physiology of motor regulation and (ii) the molecular neuropathological processes associated with PD, together with (iii) a recapitulation of the current progress in controlled DA release by nanocarriers and (iv) the design of nanozymes, catalytic nanostructures with oxidoreductase-, chaperon, and protease-like properties. Finally, we conclude by describing the prospects and knowledge gaps to overcome and consider as research into nanotherapies for PD continues, especially when clinical translations take place.

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“…However, the large device size and bulky and rigid component materials lead to constrained spatial resolution and potential brain tissue damage, limiting its practical application in in vivo studies. Recently, implantable aptamer-modified field-effect transistors were reported for monitoring serotonin or dopamine in vivo. , Although these studies represent significant progress for individual neurotransmitter monitoring, like dopamine or serotonin, it is still challenging to achieve simultaneous monitoring of different types of neurochemicals with spatiotemporal precision and molecular specificity.…”

Section: Introductionmentioning

confidence: 99%

Multiplexed Monitoring of Neurochemicals via Electrografting-Enabled Site-Selective Functionalization of Aptamers on Field-Effect Transistors

Gao

Song

et al. 2022

Anal. Chem.

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Neurochemical corelease has received much attention in understanding brain activity and cognition. Despite many attempts, the multiplexed monitoring of coreleased neurochemicals with spatiotemporal precision and minimal crosstalk using existing methods remains challenging. Here, we report a soft neural probe for multiplexed neurochemical monitoring via the electrografting-assisted site-selective functionalization of aptamers on graphene field-effect transistors (G-FETs). The neural probes possess excellent flexibility, ultralight mass (28 mg), and a nearly cellular-scale dimension of 50 μm × 50 μm for each G-FET. As a demonstration, we show that G-FETs with electrochemically grafted molecular linkers (−COOH or −NH 2 ) and specific aptamers can be used to monitor serotonin and dopamine with high sensitivity (limit of detection: 10 pM) and selectivity (dopamine sensor >22-fold over norepinephrine; serotonin sensor >17-fold over dopamine). In addition, we demonstrate the feasibility of the simultaneous monitoring of dopamine and serotonin in a single neural probe with minimal crosstalk and interferences in phosphate-buffered saline, artificial cerebrospinal fluid, and harvested mouse brain tissues. The stability studies show that multiplexed neural probes maintain the capability for simultaneously monitoring dopamine and serotonin with minimal crosstalk after incubating in rat cerebrospinal fluid for 96 h, although a reduced sensor response at high concentrations is observed. Ex vivo studies in harvested mice brains suggest potential applications in monitoring the evoked release of dopamine and serotonin. The developed multiplexed detection methodology can also be adapted for monitoring other neurochemicals, such as metabolites and neuropeptides, by simply replacing the aptamers functionalized on the G-FETs.

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Implantable Aptamer-Graphene Microtransistors for Real-Time Monitoring of Neurochemical Release in Vivo

Cited by 26 publications

References 57 publications

Flexible and Implantable Polyimide Aptamer-Field-Effect Transistor Biosensors

Flexible and Implantable Polyimide Aptamer-Field-Effect Transistor Biosensors

Nanomedicine in the Face of Parkinson’s Disease: From Drug Delivery Systems to Nanozymes

Multiplexed Monitoring of Neurochemicals via Electrografting-Enabled Site-Selective Functionalization of Aptamers on Field-Effect Transistors

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