R-3 Repository :: Browsing by Author "Robinson, Jacob"

Browsing by Author "Robinson, Jacob"

Now showing 1 - 11 of 11

Enabling Generalized Protein Therapeutics with Implantable Bioelectronics
(2023-11-16) Parker, Matthew; Robinson, Jacob
There are more than 10,000 proteins that make up the human proteome and errors in these proteins can have devastating effects on the body. Of these more than 10,000 proteins, only a small fraction are able to be isolated and provided as exogenous therapeutics to replace proteins that are deficient or abnormal. In this paper, we have developed an implantable bioelectronic system that works in conjunction with genetically modified cells to provide controlled doses of any native peptide to the patient. The implantable system protects the modified cells from any host immune response, accurately doses the therapeutic protein by modulating activation of the protein production by the cells, and ensures long-term cell viability for prolonged treatment in patients. In addition, the implant provides biometric feedback to help determine the effectiveness of the treatment and allows healthcare providers to adjust dosing without need for explantation.
Flexible microelectrodes for high quality in vivo single-unit recording
(2020-04-24) Fan, Bo; Robinson, Jacob
Single-unit recording using microelectrodes has been a key technique to help us understand how the brain functions. For long-term, high-quality and high-density recording, neural electrodes have been developed to be small and flexible to place more channels and to minimize tissue damage. However, small electrodes naturally have higher impedance, which results in higher thermal noise and reduces the recording quality. Here, we introduce a sputtered porous Pt coating for flexible microelectrodes, which is highly compatible with existing manufacturing process. We compare the sputtered porous Pt with conventional flat Pt, and find consistent impedance reduction up to 9-fold, as well as noise reduction from both in vitro (PBS solution) and in vivo (noise in suppression). We demonstrated that the porous Pt is mechanically robust for handling, implantation, recording single-unit activity and retrieval from the brain. In addition, we designed differently-shaped electrodes and found that both surface area and perimeter determine total impedance. (Adapted from Bo Fan & Alex Rodriguez et al. 2020 [1])
Lensless imaging device for microscopy and fingerprint biometric
(2020-08-25) Veeraraghavan, Ashok; Baraniuk, Richard; Robinson, Jacob; Boominathan, Vivek; Adams, Jesse; Avants, Benjamin; Rice University; United States Patent and Trademark Office
In one aspect, embodiments disclosed herein relate to a lens-free imaging system. The lens-free imaging system includes: an image sampler, a radiation source, a mask disposed between the image sampler and a scene, and an image sampler processor. The image sampler processor obtains signals from the image sampler that is exposed, through the mask, to radiation scattered by the scene which is illuminated by the radiation source. The image sampler processor then estimates an image of the scene based on the signals from the image sampler, processed using a transfer function that relates the signals and the scene.
Magnetoelectric Materials for Wireless Power Delivery to Miniature Bioelectronic Implants
(2021-04-29) Singer, Amanda; Robinson, Jacob
Advances in implanted bioelectronic technology offers the opportunity to develop more effective tools for personalized electronic medicine. While there are numerous clinical and pre-clinical applications for these devices, power delivery to these systems can be challenging. Wireless battery-free devices offer advantages such as a smaller and lighter device footprint and reduced failures and infections by eliminating lead wires. However, with the development of wireless technologies, there are fundamental tradeoffs between five essential factors: power, miniaturization, depth, alignment tolerance, and transducer distance, while still allowing devices to work within safety limits. Here I briefly discuss five existing types of wireless power transfer technologies used in bioelectronic implants - inductive coupling, radio frequency, mid-field, ultrasound, and light -and review them in context of the five tradeoffs listed above. I then add a new alternative wireless power method based on magnetoelectric (ME) materials which combines the advantages of ultrasound and inductive coupling (miniature devices activated from a distance away) to deliver therapeutic stimulation in excess of 100 Hz. I demonstrate that wireless ME stimulators provide deep brain stimulation in a freely moving rodent model for Parkinson’s disease and that these devices can be miniaturized to mm-scale and fully implanted. These results suggest ME materials are an excellent candidate to add to the fundamental types of wireless power techniques and enable miniature bioelectronics for clinical and research applications is situations where other types of wireless power transfer may be limited.
Methods for Ripple Detection and Spike Sorting During Hippocampal Replay
(2015-09-21) Sethi, Ankit; Kemere, Caleb T; Aazhang, Behnaam; Robinson, Jacob
In the rat hippocampus, fast oscillations termed sharp wave ripples and an associated sequential firing of neurons, termed replay, have been identified as playing a crucial role in memory formation and learning. The term 'replay' is used since the observed spiking encodes patterns of past experiences. To determine the role of replay in learning and decision making, a need arises for systems that can decode replay activity observed during ripples. This necessitates online algorithms for both spike sorting and ripple detection at low latencies. In my work, I have developed and tested an improved method for ripple detection and tested its performance against previous methods. Further, I have optimized a recently proposed spike sorting algorithm based on real-time bayesian inference so that it can run online in a multi-tetrode scenario, and implemented it, along with ripple detection, for the open-source electrophysiological suite, "open-ephys". The algorithm's parameters were also analyzed for their suitability in operating in an unsupervised scenario. These two modules are integrated to form a system uniquely suited to decoding neuronal sequences during sharp wave ripple events.
Microfluidic Actuation of Carbon Nanotube Fibers for Neural Recordings
(2016-11-29) Vercosa, Daniel G; Robinson, Jacob
Implantable devices to record and stimulate neural circuits have led to breakthroughs in neuroscience; however, technologies capable of electrical recording at the cellular level typically rely on rigid metals that poorly match the mechanical properties of soft brain tissue. As a result these electrodes often cause extensive acute and chronic injury, leading to short electrode lifetime. Recently, flexible electrodes such as Carbon Nanotube fibers (CNTf) have emerged as an attractive alternative to conventional electrodes and studies have shown that these flexible electrodes reduce neuro-inflammation and increase the quality and longevity of neural recordings. Insertion of these new compliant electrodes, however, remains challenge. The stiffening agents necessary to make the electrodes rigid enough to be inserted increases device footprint, which exacerbates brain damage during implantation. To overcome this challenge we have developed a novel technology to precisely implant and actuate high-performance, flexible carbon nanotube fiber (CNTf) microelectrodes without using a stiffening agents or shuttles. Instead, our technology uses drag forces within a microfluidic device to drive electrodes into tissue while minimizing the amount of fluid that is ejected into the tissue. In vitro experiments in brain phantoms, show that microfluidic actuated CNTf can be implanted at least 4.5 mm depth with 30 μm precision, while keeping the total volume of fluid ejected below 0.1 μL. As proof of concept, we inserted CNTfs in the small cnidarian Hydra littoralis and observed compound action potentials corresponding to contractions and in agreement with the literature. Additionally, brain slices extracted from transgenic mice were used to show that our device can be used to record spontaneous and light evoked activity from the cortex and deep brain regions such as the thalamic reticular nucleus (TRN). Overall our microfluidic actuation technology provides a platform for implanting and actuating flexible electrodes that significantly reduces damage during insertion.
Microfluidic Actuation of Flexible Electrodes for Neural Recordings
(2017-12-21) Vercosa, Daniel; Robinson, Jacob
Advanced technologies for neural recording have enabled breakthrough discoveries of the connectivity and functionality of the brain. However, intracortical probes for electrical interrogation at the single-cell level still rely on rigid metal or silicon components, which poorly match the mechanical properties of soft brain tissue and can therefore cause extensive tissue damage. Flexible electrodes have been shown to significantly reduce neural injury during chronic implantation and increase the quality and longevity of recordings. The need for stiffening agents to overcome the buckling force upon implantation, however, dramatically reduces the potential benefits of a small footprint and flexibility. Here, we present a novel technology to precisely implant and actuate flexible microelectrodes without a stiffening support. Our technology uses fluid flow within a microfluidic device to drive electrodes into tissue. The hydraulic design of the microdrive combined with the on-chip valves together enable precise control of the electrode position with minimal injection of fluid into the tissue. The microdrive is used to implant flexible carbon nanotube fiber (CNTf) electrodes in the small cnidarian Hydra and interrogate its neural circuits during spontaneous behavior. Using rodent brain slices, we also recorded spatially confined light-evoked neural activity in deep brain regions, demonstrating the precision of probe positioning provided by the microdrive. Finally, performing minor modifications to the device geometry and connection strategy allowed us to record single-unit activity in the cortex and subcortical regions of anesthetized rats, showing that this novel technology can also be used in vivo, with a potential impact on mitigating neuro-inflammation and improving chronic electrode stability.
Novel Mechanisms for Magnetogenetic Neuromodulation
(2017-10-24) Polali, Sruthi; Robinson, Jacob; Natelson, Douglas; Clementi, Cecilia; Kemere, Caleb
Magnetogenetic tools permit wireless stimulation of specific neurons located deep inside the brain of freely moving animals: a capability that improves the study of neural activity and its correlation to behavior. Recently, a fully genetically encoded, magnetically sensitive protein chimera consisting of ferritin and TRPV4, dubbed Magneto2.0, was shown to elicit action potentials in neurons when exposed to a magnetic field. The iron-sequestering protein, ferritin serves as the magnetically sensitive domain in this chimera, while TRPV4 is a cation selective channel that responds to mechanical and temperature stimuli. While it was suggested that the mode of operation was through mechanical stimulation of the channel by ferritin, later calculations show that the forces exerted by ferritin nanoparticles are orders of magnitude lower than what is required for channel gating. We propose an alternate mechanisms based on the magnetocaloric effect to explain how paramagnetic ferritin could gate the thermally sensitive TRPV4. A magnetic field reduces the entropy of the ferritin nanoparticles when its magnetic spins align, resulting in an increase in temperature that in turn gates the heat-sensitive TRPV4 channel. We support our theory with calculations and experimental data that demonstrate that the observed responses are indeed thermally mediated. To further prove the magnetocaloric mechanism, we designed a novel magnetogenetic channel consisting of fusion of ferritin and cold-sensitive channel TRPM8, dubbed MagM8. This channel is activated due to decrease in temperature caused by increase in entropy during demagnetization of ferritin. In addition to reconciling biological observations with physical properties of genetically encoded magnetic nanoparticles, our explanation will also aid the design of new magnetogenetic tools with improved magnetic sensitivity.
Optimization of Fast Multiplexed Magnetogenetics
(2021-04-30) Sebesta, Charles; Robinson, Jacob
Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here I demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Additionally, I have identified novel TRPA1 channels that show promise of translating this work into mammalian systems. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, I can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.
Real-time In Vitro and In Vivo Biosensing using Photonic Microring Resonators
(2023-04-18) Hassan, Sakib; Robinson, Jacob
Real-time in vivo detection of different bioanalyte and biomarkers, particularly nitric oxide (NO) and temperature, is of utmost importance for critical healthcare monitoring, therapeutic dosing, and fundamental understanding of their role in regulating many physiological processes. However, the detection of NO in a biological medium is challenging due to its short lifetime and low concentration. Traditional methods of detecting bioanalyte and biomarkers suffer from many limitations such as complex sample preparation, complicated and expensive instrumentation, electromagnetic interference, etc. Here, we demonstrate for the first time that photonic Micro Ring Resonators (MRRs) can provide real-time, direct, and in vivo detection of NO in a mouse wound model. The MRR encodes the NO concentration information into its transfer function in the form of a resonance wavelength shift. We show that these functionalized MRRs, fabricated using CMOS-compatible processes, can achieve sensitive detection of NO (sub-µM) with excellent specificity, and no apparent performance degradation over more than 24 hours of operation in the biological medium. In another study, we show that this MRR can measure magnetic nanoparticle heating with high precision and fast temporal resolution (10 µs). MRR has negligible thermal mass and is not affected by electromagnetic interference; therefore, it can provide a more accurate measurement of specific absorption rate for sample volume as small as a few µL. We also demonstrate that MRR can measure the temperature gradient of a sample substrate with high spatial resolution and is capable of measuring the multiplexing capability of dual-channel magnetic nanoparticles. Finally, we could successfully measure the temperature of the targeted region of the brain slice during AMF stimulation which is not possible with traditional methods. Therefore, with alternative functionalization, this compact lab-on-chip optical sensing platform could support the real-time detection of myriad biochemical species and biomarkers and can revolutionize the field of biomedical science and healthcare monitoring.
Embargo
Rigid and Flexible Integrated Photonics for Optical Biosensing
(2023-11-20) Zhao, Xuan; Robinson, Jacob
Biosensing of physiological signals, such as the body temperature and biomolecules, are of critical importance to disease monitoring, diagnosis, and treatment, in both clinical and research settings. Optical biosensors in particular have shown unique advantages when compared with traditional electrochemical sensors—optical sensors are electromagnetic interference (EMI) free, resistant to electroactive interferants, while exhibiting both sensitivity and specificity. Integrated photonics based on the refractive index sensing mechanism is one promising example of compact optical biosensing, with high sensitivity, specificity, and label-free operation. Moreover, these integrated photonic sensors can have ultrasmall form factors and be manufactured at low costs, thanks to their CMOS-fabrication compatibility. In the first part of the thesis, we demonstrate a rigid, silicon-on-insulator-based integrated photonic biosensor for high-sensitivity glucose detection. We show that by functionalization of receptors on a micro-ring resonator (MRR) sensor surface, the MRR sensor is able to reach the limit of detection for non-invasive glucose sensing in saliva and tears. Moreover, we show that the MRR sensor responds minimally to common interferents present in biofluids and performs stably across a wide pH range compared with enzyme-based electrochemical sensors. These results could potentially facilitate the development of a low-cost, benchtop optical platform for non-invasive diabetes screening. Although SOI-based integrated photonic sensors can detect biomolecules with a high LOD and specificity, the sensor’s mechanical rigidity has largely limited its applications to in vitro, benchtop settings. In the second part of the thesis, we demonstrate a flexible integrated photonic platform that is better suited for in vivo biological applications. We show that by utilizing TiO2 as the core material and SU-8 polymer as the flexible cladding, the flexible photonic MRR sensors are capable of high-sensitivity temperature sensing. More importantly, we show that the flexible photonic sensor can be surface-functionalized through a generalized, polymer-compatible approach for biochemical detection with sub-uM sensitivity. The successful demonstration of our sensors is a key step toward developing more biocompatible, conformal, and flexible photonic platforms for next-generation biosensing applications that require tissue contact or device implantation.

Browsing by Author "Robinson, Jacob"

Results Per Page

Sort Options