An official website of the United States government
Fast electrochemical imaging enables the dynamic study of electroactive molecule diffusion in neurotransmitter release from single cells and dopamine mapping in brain slices. In this paper, we discuss the design of an electrochemical imaging sensor using a monolithic CMOS sensor array and a multifunctional data acquisition system. Using post-CMOS fabrication, the CMOS sensor integrates 1024 on-chip electrodes on the surface and contains 1024 low-noise amplifiers to simultaneous process parallel electrochemical recordings. Each electrochemical electrode and amplifier are optimized to operate at 10.38 kHz sampling rate. To support the operation of the high-throughput CMOS device, a multifunctional data acquisition device is developed to provide the required speed and accuracy. The high analog data rate of 10.63 MHz from all 1024 amplifiers is redundantly sampled by the custom-designed data acquisition system which can process up to 73.6 MHz with up to ~400 Mbytes/s data rate to a computer using USB 3.0 interface. To contain the liquid above the electrochemical sensors and prevent electronic and wire damage, we packaged the monolithic sensor using a 3D-printed well. Using the presented device, 32 pixel × 32 pixel electrochemical imaging of dopamine diffusion is successfully demonstrated at over 10,000 frames per second, the fastest reported to date.
more »
« less
On-chip Detection of Single Vesicle Release from Neuroblastoma Cells using Monolithic CMOS Bioelectronics
Neuroblastoma cells are often used as a cell model to study Parkinson's disease, which causes reduced dopamine release in substantia nigra, the midbrain that controls movements. In this paper, we developed a 1024-ch monolithic CMOS sensor array that has the spatiotemporal resolution as well as low-noise performance to monitor single vesicle release of dopamine from neuroblastoma cells. The CMOS device integrates 1024 on-chip electrodes with an individual size of 15 μm × 15 μm and 1024 transimpedance amplifiers for each electrode, which are each capable of measuring sub-pA current. Thus, this device can be used to study the detailed molecular dynamics of dopamine secretion at single vesicle resolution.
more »
« less
- Award ID(s):
- 1745364
- PAR ID:
- 10087750
- Date Published:
- Journal Name:
- 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
- Page Range / eLocation ID:
- 5065 to 5068
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Electrochemical sensing arrays enable the spatial study of dopamine levels throughout brain slices, the diffusion of electroactive molecules, as well as neurotransmitter secretion from single cells. The integration of complementary metal-oxide semiconductor (CMOS) devices in the development of electrochemical sensing devices enables large-scale parallel recordings, providing beneficial high-throughput for drug screening studies, brain–machine interfaces, and single-cell electrophysiology. In this paper, an electrochemical sensor capable of recording at 40,000 frames per second using a CMOS sensor array with 1024 electrochemical detectors and a custom field-programmable gate array data acquisition system is detailed. A total of 1024 on-chip electrodes are monolithically integrated onto the designed CMOS chip through post-CMOS fabrication. Each electrode is paired with a dedicated transimpedance amplifier, providing 1024 parallel electrochemical sensors for high-throughput studies. To support the level of data generated by the electrochemical device, a powerful data acquisition system is designed to operate the sensor array as well as digitize and transmit the output of the CMOS chip. Using the presented electrochemical sensing system, both dopamine and hydrogen peroxide diffusions across the sensor array are successfully recorded at 40,000 frames per second across the 32 × 32 electrochemical detector array.more » « less
-
In the study of the brain, large and high-density microelectrode arrays have been widely used to study the behavior of neurotransmission. CMOS technology has facilitated these devices by enabling the integration of high-performance amplifiers directly on-chip. Usually, these large arrays measure only the voltage spikes resulting from action potentials traveling along firing neuronal cells. However, at synapses, communication between neurons occurs by the release of neurotransmitters, which cannot be measured on typical CMOS electrophysiology devices. Development of electrochemical amplifiers has resulted in the measurement of neurotransmitter exocytosis down to the level of a single vesicle. To effectively monitor the complete picture of neurotransmission, measurement of both action potentials and neurotransmitter activity is needed. Current efforts have not resulted in a device that is capable of the simultaneous measurement of action potential and neurotransmitter release at the same spatiotemporal resolution needed for a comprehensive study of neurotransmission. In this paper, we present a true dual-mode CMOS device that fully integrates 256-ch electrophysiology amplifiers and 256-ch electrochemical amplifiers, along with an on-chip 512 electrode microelectrode array capable of simultaneous measurement from all 512 channels.more » « less
-
Dopamine (DA) is an important neurotransmitter, which is essential for transmitting signals in neuronal communications. The deficiency of DA release from neurons is implicated in neurological disorders. There has been great interest in developing new optical probes for monitoring the release behavior of DA from neurons. H-aggregates of organic dyes represent an ordered supramolecular structure with delocalized excitons. In this paper, we use the self-assembly of 3,3′-diethylthiadicarbocyanine iodide (DiSC 2 (5)) in ammonia solution to develop crystalline H-aggregate nanoparticles, in which DiSC 2 (5) molecules show long-range π–π stacking. The crystalline H-aggregate nanoparticles are stable in cell culture medium and can serve as an efficient photo-induced electron transfer (PET) probe for the detection of DA with the concentration as low as 0.1 nM in cell culture medium. Furthermore, the crystalline H-aggregate nanoparticle-based PET probe is used to detect the release behavior of DA from the M17 human neuroblastoma cells. We find that the DA release from the cells is enhanced by nicotine stimulations. Our results highlight the potential of crystalline H-aggregate nanoparticle-based PET probes for diagnosing nervous system diseases and verifying therapies.more » « less
-
Abstract Modulatory mechanisms of neurotransmitter release and clearance are highly controlled processes whose finely tuned regulation is critical for functioning of the nervous system. Dysregulation of the monoamine neurotransmitter dopamine can lead to several neuropathies. Synaptic modulation of dopamine is known to involve pre‐synaptic D2 auto‐receptors and acid sensing ion channels. In addition, the dopamine membrane transporter (DAT), which is responsible for clearance of dopamine from the synaptic cleft, is suspected to play an active role in modulating release of dopamine. Using functional imaging on theCaenorhabditis elegansmodel system, we show that DAT‐1 acts as a negative feedback modulator to neurotransmitter vesicle fusion. Results from our fluorescence recovery after photo‐bleaching (FRAP) based experiments were followed up with and reaffirmed using swimming‐induced paralysis behavioral assays. Utilizing our numerical FRAP data we have developed a mechanistic model to dissect the dynamics of synaptic vesicle fusion, and compare the feedback effects of DAT‐1 with the dopamine auto‐receptor. Our experimental results and the mechanistic model are of potential broader significance, as similar dynamics are likely to be used by other synaptic modulators including membrane transporters for other neurotransmitters across species.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1109/EMBC.2018.8513219
