Biology subjects

Jacinto, L.

Publications and source records attributed to Jacinto, L..

8 recordsLinked to original sources

bioRxiv2026

BOWIe: Wireless Headstage for Optical Stimulation in Closed-Loop Optogenetics Experiments in Freely-moving Rodents

Optogenetics is an invaluable technique in neuroscience to study brain circuits, but conventional optogenetic systems use tethered approaches to deliver light to the brain which can hinder natural behavior. Optoelectronic advances led to the development of wireless optical stimulators for optogenetics experiments, but most reported devices have low widespread use due to complex builds and reduced versatility, which has also limited their integration in closed-loop systems. Here, we developed BOWIe, a battery-powered, low-weight, wireless headstage for photostimulation in optogenetics experiments with rodents, especially designed for simple integration in multiple behavioral setups, including those requiring closed-loop operation. BOWIe is based on a Bluetooth-Low Energy system-on-a-chip that allows simultaneous control and communication capabilities with a reduced number of components, and can be paired with an Arduino-based transmitter for simple integration in any behavioral paradigm using analogue or digital triggers. Two modes of optical stimulation are possible, either with ferrule-coupled optical fibers or LED neural probes, which permit adapting the headstage according to material availability or experimental demands. A user-friendly app was also developed to simplify headstage pairing, definition of stimulation parameters, and protocol design. BOWIe was validated in two behavioral paradigms, including in a closed-loop experiment using computer vision, Bonsai RX, and Deeplabcut Live to track behavioral parameters online and remotely trigger photostimulation upon detected events. BOWIe's modular design and flexible integration with behavioral setups make it a practical tool for in vivo experiments with optogenetics.

bioengineering↗

bioRxiv2026

NeoDBS: Open-Source Platform for Visualization and Analysis of Electrophysiological Recordings from Deep Brain Stimulation Systems

Optimization of deep brain stimulation (DBS) therapy for neurological and neuropsychiatric disorders depends on objective quantitative biomarkers that can guide stimulation parameter adjustments. With the recent introduction of new-generation DBS systems capable of simultaneously stimulating brain activity and recording local field potentials (LFP), there is increasing demand for platforms that enable efficient visualization and analysis of these signals for electrophysiological biomarkers identification. To address the limitations of currently available toolboxes that require advanced signal processing skills and rely on proprietary software, we present NeoDBS, an open-source Python platform designed for ingestion and advance signal visualization and processing of LFP signals from DBS systems through an easy-to-use graphical interface. NeoDBS is a user-centered platform that offers predefined analysis pipelines with the aim of facilitating electrophysiological biomarker investigation for DBS across different brain disorders. Custom analysis pipelines are also available for users to leverage the signal analysis tools to their research needs. Critical functionalities for longitudinal biomarker research are featured in NeoDBS, such as batch file processing and event-locked analysis for in-clinic and at-home recordings. This combination of accessibility, user-experience and advanced signal processing tools makes NeoDBS an environment that propels easy and fast electrophysiological biomarker research for DBS, across patients, sessions, and stimulation parameters.

bioengineering↗

bioRxiv2025

Ultrasensitive graphene FET aptasensor for direct attomolar detection of glutamate in human clinical samples

Glutamate, the principal excitatory neurotransmitter in the brain, is crucial for cognition and memory, and its dysregulation is implicated in several neurological disorders, including Alzheimers Disease and epilepsy. However, precise and high-throughput quantification of glutamate in physiological samples remains challenging. Here, we report an ultrasensitive and highly specific glutamate aptamer-based biosensor, or aptasensor, developed through in silico design and microfabrication, followed by in vitro and clinical validation. The biosensor consists of arrays of graphene field-effect transistors functionalized with a novel DNA aptamer, NG-Apt-Glu, designed and characterized computationally and biochemically, revealing two putative glutamate binding sites. The aptasensor detects glutamate in artificial cerebrospinal fluid with a 1 aM detection limit, a wide linear range (1 aM-10 pM), and 24 mV/decade sensitivity, showing strong selectivity against GABA, glutamine, dopamine, and serotonin. To evaluate clinical applicability, glutamate levels were measured in cerebrospinal fluid from patients with Alzheimers Disease, showing a significant increase relative to controls and correlating with neurofilament light chain concentrations, a biomarker of neuronal death. These findings underscore glutamates involvement in Alzheimers pathophysiology and its potential as a biomarker for neurodegeneration. This ultrasensitive graphene-based aptasensor enables point-of-care monitoring, paving the way for early diagnosis and the development of novel therapeutic strategies.

bioengineering↗

bioRxiv2024

Small form factor implantable neural probe with efficient flip chip micro LED for in vivo optogenetics

Optogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (LEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate LEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip LEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm2 but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm2. Due to the high plug efficiency of the LED, the neural probe can perform stimulation protocols up to 20 Hz and 80% duty cycles without surpassing estimated hotspot temperature elevations above 1 {o}C. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic mice being reliably modulated by pulsed light emitted from the probe.

bioengineering↗

bioRxiv2022

Ultrasensitive Dopamine Detection with Graphene Aptasensor Multitransistor Arrays

Dopamine is a neurotransmitter with critical roles in the human brain and body, and abnormal dopamine levels underlie brain disorders such as Parkinsons Disease, Alzheimers Disease, and substance addiction. Herein, we present a novel high-throughput biosensor based on graphene multitransistor arrays (gMTAs) functionalized with a selective aptamer for robust ultrasensitive dopamine detection. The miniaturized biosensor integrates multiple electrolyte-gated graphene field-effect transistors (EG-gFETs) in an array configuration, fabricated by high-yield reproducible and scalable methodologies optimized at the wafer level. With these gMTA aptasensors, we reliably detected ultra-low dopamine concentrations in physiological buffers, including undiluted phosphate-buffered saline (PBS), artificial cerebral spinal fluid (aCSF), and high ionic strength complex biological samples. We report a record limit-of-detection (LOD) of 1 aM (10-18) for dopamine in both PBS, and dopamine-depleted brain homogenate samples spiked with dopamine. The gMTAs also display wide sensing ranges across all media, up to 100 M (10-8), with a 22 mV/decade peak sensitivity in aCSF. Furthermore, we show that the gMTAs can detect minimal changes in dopamine concentrations in small working volume biological CSF samples obtained from a mouse model of Parkinsons Disease.

bioengineering↗

bioRxiv2021

Hybrid multisite silicon neural probe with integrated flexible connector for interchangeable packaging

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes, in particular, allow the integration of complex probe geometries, such as multi-shank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from the highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multi-shank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized on wafer level and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 m-thick highly flexible polyimide interconnect cable were produce. To avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility since interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).

bioengineering↗

bioRxiv2020

Double-layer flexible neuronal probe with closely spaced electrodes for high-density in vivo brain recordings

Flexible probes for brain activity recordings are an attractive emerging approach that reduces mechanical mismatch between probe and neuronal tissue, thus minimizing the risk of brain damage or glial scaring. Although promising, flexible probes still present some technical challenges namely: i) how to overcome probe buckling during brain insertion given its intrinsically low mechanical rigidity; ii) how to fabricate closely spaced electrode configurations for high density recordings by standard lithography techniques in the flexible substrate. Here, we present a new flexible probe based solely on standard and low-cost lithography processes, which has closely spaced 10 m diameter gold electrode sites on a polyimide substrate with inter-site distances of only 5 m. By using a double-layer design and fabrication approach we were able to accommodate closely spaced electrode sites at two different depths from probe surface while also providing additional stiffening, just sufficient to prevent probe buckling during brain insertion. Detailed probe characterization through metrology of structural and electrical properties and chemical composition analysis, as well as functional assessment through in vivo high-density recordings of neuronal activity in the mouse cortex, confirmed the viability of this new fabrication approach and that this probe can be used for obtaining high quality brain recordings with excellent signal-to-noise ratio (SNR).

bioengineering↗

bioRxiv2020

A versatile and modular tetrode-based device for single-unit recordings in rodent ex vivo and in vivo acute preparations

The demand for affordable tools for recording extracellular activity and successfully isolating single units from different brain preparations has pushed researchers and companies to invest in developing and fabricating new recording devices. However, depending on the brain region of interest, experimental question or type of preparations, different devices are required thus adding substantial financial burden to laboratories. We have developed a simple and affordable tetrode-based device that allows interchangeable extracellular recordings of neural activity between in vivo and ex vivo preparations and can be easily implemented in all wet-bench laboratories. Spontaneous activity from several putative single neurons could be easily recorded and isolated by lowering the device into ex vivo cerebellum brain slices. The same device was also used in vivo, lowered into primary auditory cortex of adult anesthetized transgenic mice expressing channelrhodopsin in cortical neurons. Acoustic stimulation of the contralateral ear or direct laser optogenetic stimulation successfully evoked cortical activity at the recording site. Several isolated putative single neurons presented time-locked activity response to the different stimuli. In summary, we developed an affordable, versatile and modular device to facilitate tetrode extracellular recordings interchangeably between in vivo anaesthetized animals and ex vivo brain slice recordings. HighlightsDeveloped a versatile and modular device to facilitate tetrode acute brain recordings interchangeably between in vivo and ex vivo preparations. Conducted ex vivo extracellular recordings in acute cerebellar slices. Conducted in vivo extracellular recordings in auditory cortex of anaesthetized mice. Recorded and isolated multiple single units in both acute slices and anaesthetized mice recordings using the same device. Device can be easily extended to accommodate optic fiber and cannula.

neuroscience↗