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{1384}
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ref: -0 tags: NET probes SU-8 microfabrication sewing machine carbon fiber electrode insertion mice histology 2p date: 12-29-2017 04:38 gmt revision:1 [0] [head]

PMID-28246640 Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

  • SU-8 asymptotic H2O absorption is 3.3% in PBS -- quite a bit higher than I expected, and higher than PI.
  • Faced yield problems with contact litho at 2-3um trace/space.
  • Good recordings out to 4 months!
  • 3 minutes / probe insertion.
  • Fab:
    • Ni release layer, Su-8 2000.5. "excellent tensile strength" --
      • Tensile strength 60 MPa
      • Youngs modulus 2.0 GPa
      • Elongation at break 6.5%
      • Water absorption, per spec sheet, 0.65% (but not PBS)
    • 500nm dielectric; < 1% crosstalk; see figure S12.
    • Pt or Au rec sites, 10um x 20um or 30 x 30um.
    • FFC connector, with Si substrate remaining.
  • Used transgenic mice, YFP expressed in neurons.
  • CA glue used before metabond, followed by Kwik-sil silicone.
  • Neuron yield not so great -- they need to plate the electrodes down to acceptable impedance. (figure S5)
    • Measured impedance ~ 1M at 1khz.
  • Unclear if 50um x 1um is really that much worse than 10um x 1.5um.
  • Histology looks realyl great, (figure S10).
  • Manuscript did not mention (though the did at the poster) problems with electrode pull-out; they deal with it in the same way, application of ACSF.

{1062}
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ref: Kim-2008.01 tags: PEDOT review soft date: 12-29-2017 04:34 gmt revision:4 [3] [2] [1] [0] [head]

PMID-21204405 Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devices.

  • lays out the soft electrode approach (obviously).
  • Extensive discussion of conductive polymer plating methods for neural electrodes.

____References____

[0] Kim DH, Richardson-Burns S, Povlich L, Abidian MR, Spanninga S, Hendricks JL, Martin DC, Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devicesno Source no Volume no Issue no Pages (2008)

{1010}
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ref: Salcman-1973.07 tags: Salcman MEA microelectrodes chronic recording glass cyanocrylate date: 12-29-2017 04:33 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-4708761 Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes

  • Teflon-coated 25um Pt-Ir (90/10)
  • Heat fuse this with a glass micropipette & backfill with cyanoacrylate. {1011}
    • Isobutyl acrylate is hydrolysed more slowly and hence is less toxic to the surronding tissue
    • cyanoacrylate is apparently biodegradable.
  • Durable, stable: one electrode displayed a single cortical spike (though not necessarily the same one) for more than 90 consecutive days.
  • unacceptably low impedance = 100K or less
  • Unit activity was present only 10-24H after surgery.
  • formal review of even older microelectrode studies.
  • 10nA should be 100x too small to have any effect on a platinum tip [17]
  • A seperable cell with a SNR of 3:1 would become lost if the electrode tip moved 15um away from a 20um soma.
    • "It becomes clear that the problem of holding single units for prolonged periods in the unrestrained animal is not achieved without considerable difficulty". Yet they think they have solved it.

____References____

Salcman, Michael and Bak, Martin J. Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 253 -260 (1973)

{1400}
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ref: -0 tags: robinson pasquali carbon nanotube fiber fluidic injection dextran neural electrode date: 12-28-2017 04:20 gmt revision:0 [head]

PMID-29220192 Fluidic Microactuation of Flexible Electrodes for Neural Recording.

  • Use viscous dextran solution + PDMS channel system
  • Durotomy (of course)
  • Parylene-C insulated carbon fiber electrodes, cut with FIB or razor blade
  • Used silver ink to electrically / mechanically attach for recordings.
  • Tested in hydra, rat brain slice (reticular formation of thalamus), and in-vivo rat.
  • Electrodes, at 12um diameter, E=120GPa, are approximately 127x stiffer than one 4x20um PI (E=9GPa) probe. Less damage though.

{1368}
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ref: -0 tags: Lieber nanoFET review silicon neural recording intracellular date: 12-28-2017 04:04 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-23451719 Synthetic Nanoelectronic Probes for Biological Cells and Tissue

  • Review of nanowireFETS for biological sensing
  • Silicon nanowires can be grown via vapor-liquid-solid or vapor-solid-solid, 1D catalyzed growth, usually with a Au nanoparticle.
  • Interestingly, kinks can be introduced via "iterative control over nucleation and growth", 'allowing the synthesis of complex 2D and 3D structures akin to organic chemistry"
    • Doping can similarly be introduced in highly localized areas.
    • This bottom-up synthesis is adaptable to flexible and organic substrates.
  • Initial tests used polylysine patterning to encourage axonal and dendritic growth across a nanoFET.
    • Positively charged amino group interacts with negative surface charge phospholipid
    • Lieber's group coats their SU-8 electrodes in poly-d-lysine as well {1352}
  • Have tested multiple configurations of the nanowire FET, including kinked, one with a SiO2 nanopipette channel for integration with the cell membrane, and one where the cell-attached fluid membrane functions as the semiconductor; see figure 4.
    • Were able to show recordings as one of the electrodes was endovascularized.
  • It's not entirely clear how stable and scalable these are; Si and SiO2 gradually dissolve in physiological fluid, and no mention was made of longevity.

{1176}
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ref: Gilgunn-2012 tags: kozai neural recording electrodes compliant parylene flexible dissolve date: 12-28-2017 03:50 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-6170092 (pdf) An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

    • Optical coherence tomography is cool.
  • Large footprint - 150 or 300um, 135um thick (13500 or 40500 um^2; c.f. tungsten needle 1963 (50um) or 490 (25um) um^2.)
  • Delivery vehicle is fabricated from biodissolvable carboxy-methylcellulose (CMC).
    • Device dissolves within three minutes of implantation.
    • Yet stiff enough to penetrate the dura of rats (with what degree of dimpling?)
    • Lithographic patterning process pretty clever, actually.
    • Parylene-X is ~ 1.1 um thick.
    • 500nm Pt is patterned via ion milling with a photoresist mask.
    • Use thin 20nm Cr etch mask for both DRIE (STS ICP) and parylene etch.
  • Probes are tiny -- 10um wide, 2.7um thick, coated in parylene-X.
  • CMC polymer tends to bend and warp due to stress -- must be clamped in a special jig.
  • No histology. Follow-up: {1399}

{1236}
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ref: -0 tags: optogenetics micro LED flexible electrodes PET rogers date: 12-28-2017 03:24 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-23580530 Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

  • Supplementary materials
  • 21 authors, University Illinois at Urbana-Champaign, Tufts, China, Northwestern, Miami ..
  • GaN blue and green LEDs fabricated on a flexible substrate with stiff inserter.
    • Inserter is released in 15 min with a dissolving silk fibrin.
    • made of 250um thick SU-8 epoxy, reverse photocured on a glass slide.
  • GaN LEDS fabricated on a sapphire substrate & transfer printed via modified Karl-Suss mask aligner.
    • See supplemental materials for the intricate steps.
    • LEDs are 50um x 50um x 6.75um
  • Have integrated:
    • Temperature sensor (Pt serpentine resistor) / heater.
    • inorganic photodetector (IPD)
      • ultrathin silicon photodiode 1.25um thick, 200 x 200um^2, made on a SOI wafer
    • Pt extracellular recording electrode.
        • This insulated via 2um thick more SU-8.
  • Layers are precisely aligned and assembled via 500nm layer of epoxy.
    • Layers made of 6um or 2.5um thick mylar (polyethylene terephthalate (PET))
    • Layers joined with SU-8.
    • Wiring patterned via lift-off.
  • Powered via RF scavenging at 910 Mhz.
    • appeared to be simple, power in = light out; no data connection.
  • Tested vs control and fiber optic stimulation, staining for:
    • Tyrosine hydroxylase (makes l-DOPA)
    • c-fos, a neural activity marker
    • u-LEDs show significant activation.
  • Also tested for GFAP (astrocytes) and Iba1 (activated microglia); flexible & smaller devices had lower gliosis.
  • Next tested for behavior using a self-stimulation protocol; mice learned to self-stimulate to release DA.
  • Devices are somewhat reliable to 250 days!

{1399}
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ref: -0 tags: kozai CMC dissolving insertion shuttle parylene date: 12-28-2017 03:19 gmt revision:1 [0] [head]

PMID-25128375 Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes.

  • CMC = carboxymethyl cellulose, commonly used as a food additive, in toothpaste, etc.
  • To address CMC dissolution, we developed a sophisticated targeting, high speed insertion (∼80 mm/s), and release system to implant shuttles.
  • Cross section of the probes are large, 300 x 125um and 100 x 125um.
  • Beautiful histology: the wound does gradually close up as the CMC dissolves, but no e-phys.

{1057}
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ref: Kozai-2009.11 tags: electrodes insertion Kozai flexible polymer momolayer date: 12-28-2017 02:59 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-19666051[0] Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.

  • This study investigated the use of an electronegative (hydrophillic) self-assembled monolayer (SAM) as a coating on a stiff insertion shuttle to carry a polymer probe into the cerebral cortex, and then the detachment of the shuttle from the probe by altering the shuttle's hydrophobicity.
    • Used 11-mercaptoundecanoic acid.
    • Cr/Au (of course) evaporated on 15um thick Si shuttle.
    • SAM attracts water once inserted, causing the hydrophobic polymer to move away.
      • Why not make the polymer hydrophillic?
      • Is this just soap?
  • Used agarose brain model.
  • Good list of references for the justification of soft electrodes, and researched means for addressing this, mostly usnig polymer stiffeners.
    • "Computer models and experimental studies of the probe–tissue interface suggest that flexible and soft probes that approach the brain’s bulk material characteristics may help to minimize micromotion between the probe and surrounding tissue ({737}; {1203}; {1102}; {1200}; LaPlaca et al., 2005; {1216}; Neary et al., 2003 PMID-12657694; {1198})"
  • "However, polymer probes stick to metallic and silicon surfaces through hydrophobic interactions, causing the polymer probe to be carried out of the brain when the insertion shuttle is removed. The solution is to use a highly hydrophillic, electronegative, self-assembled monolayer coating on the shuttle.
  • Biran et al 2005 suggests that incremental damage due to stab wounds from the shuttle (needle) should be minor.
  • Probes: 12.5 um thick, 196 um wide, and 1.2cm long, polymide substrate and custom designed lithographed PDMS probes.
  • Polymer probes were inserted deep - 8.5 mm.
  • PDMS probes inserted with non-coated insertion shuttle resulted in explantation of the PDMS probe.

____References____

[0] Kozai TD, Kipke DR, Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.J Neurosci Methods 184:2, 199-205 (2009 Nov 15)

{1398}
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ref: -0 tags: platinum parylene electrodes brush dissolving stiffener gelatin date: 12-28-2017 02:44 gmt revision:0 [head]

PMID-27159159 Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers.

  • 12.5um pure Pt wires
  • Coated in 4um parylene-C
  • stiffened with gelatin
  • further protected with Kollicoat to retard dissolution.
  • Used a pulsed UV laser to ablate parylene, cut the platinum, and roughen the recording site.
  • See also {311}

{1397}
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ref: -0 tags: polyimide electrodes immune response foreign body inflammation stiffener steiglitz date: 12-28-2017 02:37 gmt revision:0 [head]

PMID-27534649 Intracortical polyimide electrodes with a bioresorbable coating.

  • Molten saccharose was used as coating material.
  • 270 x 10um polyimide recording probes. (large!)
  • Tissue reaction seems to peak at 2 weeks-4weeks, and decline somewhere thereafter. (though there were not a great number of samples.)

{1396}
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ref: -0 tags: rogers thermal oxide barrier neural implants ECoG coating accelerated lifetime test date: 12-28-2017 02:29 gmt revision:0 [head]

PMID-27791052 Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems

  • Thermal oxide proved the superior -- by far -- water barrier for encapsulation.
    • What about the edges?
  • Many of the polymer barrier layers look like inward-rectifiers:
  • Extensive simulations showing that the failure mode is from gradual dissolution of the SiO2 -> Si(OH)4.
    • Even then a 100nm layer is expected to last years.
    • Perhaps the same principle could be applied with barrier metals. Anodization or thermal oxidation to create a thick, nonporous passivation layer.
    • Should be possible with Al, Ta...

{1395}
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ref: -0 tags: Courtine e-dura PDMS silicone gold platinum composite stretch locomotion restoration rats date: 12-22-2017 01:59 gmt revision:0 [head]

PMID-25574019 Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.

  • Fabrication:
    • 120um total PDMS thickness, made through soft lithography, covalent (O2 plasma) bonding between layers
    • 35nm of Au (thin!) deposited through a stencil mask.
    • 300um Pt-PDMS composite for electrode sites, deposited via screenprinting
  • 100 x 200um cross section drug delivery channel.
  • Compared vs. stiff 25um thick PI film electrode.
    • stiff implants showed motor impairments 1-2 weeks after implantation.
  • Showed remarkable recovery of supported locomotion with stimulation and drug infusion (to be followed by monkeys).

{1394}
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ref: -0 tags: Courtine PDMS soft biomaterials spinal cord e-dura date: 12-22-2017 01:29 gmt revision:0 [head]

Materials and technologies for soft implantable neuroprostheses

  • Quote: In humans, both the spinal cord and its meningeal protective membranes can experience as much as 10–20% tensile strain and
displacement (relative to the spinal canal) during normal postural movements. This motion corresponds to displacements on the order of centimetres17. The deformations relative to the spinal cord in animal models, such as rodents or non-human primates, are likely to be even larger.

{1393}
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ref: -2001 tags: polyimide Kipke bioactive flexible electrode arrays date: 12-22-2017 01:16 gmt revision:2 [1] [0] [head]

PMID-11327505 Flexible polyimide-based intracortical electrode arrays with bioactive capability.

  • Appears to be the first or one of the first use of thin-film polyimide for intracortical recording; will have to cite.
  • Fab protocol: 500nm release thermal oxide, photo-paternable PI, Cr-Au metalization, O2 plasma de-scum for adhesion (ish?), <20um total thickness.
  • Conductive epoxy attachment to connector.

{1392}
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ref: -0 tags: lieber mesh electronics SU-8 recording electrodes flexible polymer glass capillary date: 12-22-2017 00:14 gmt revision:0 [head]

PMID-29109247 Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

  • Key change was the addition of multiple conductor traces per longitudinal mesh line; this allows them to get 64 or 128 channels per mesh without a dramatic increase in modulus.
  • The latitudinal / diagonal lines still displace tissue ...
  • And the injection mechanism, glass pipette, 650um OD, 400um ID, is pretty large, even for 128 channels.
  • Use carbon nanotube ink, custom CNC printer, to connect to FPC.
    • Pretty impressive that they can manipulate ~800nm thick Su-8 film intraop and have it work well!

{1391}
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ref: -0 tags: computational biology evolution metabolic networks andreas wagner genotype phenotype network date: 06-12-2017 19:35 gmt revision:1 [0] [head]

Evolutionary Plasticity and Innovations in Complex Metabolic Reaction Networks

  • ‘’João F. Matias Rodrigues, Andreas Wagner ‘’
  • Our observations suggest that the robustness of the Escherichia coli metabolic network to mutations is typical of networks with the same phenotype.
  • We demonstrate that networks with the same phenotype form large sets that can be traversed through single mutations, and that single mutations of different genotypes with the same phenotype can yield very different novel phenotypes
  • Entirely computational study.
    • Examines what is possible given known metabolic building-blocks.
  • Methodology: collated a list of all metabolic reactions in E. Coli (726 reactions, excluding 205 transport reactions) out of 5870 possible reactions.
    • Then ran random-walk mutation experiments to see where the genotype + phenotype could move. Each point in the genotype had to be viable on either a rich (many carbon source) or minimal (glucose) growth medium.
    • Viability was determined by Flux-balance analysis (FBA).
      • In our work we use a set of biochemical precursors from E. coli 47-49 as the set of required compounds a network needs to synthesize, ‘’’by using linear programming to optimize the flux through a specific objective function’’’, in this case the reaction representing the production of biomass precursors we are able to know if a specific metabolic network is able to synthesize the precursors or not.
      • Used Coin-OR and Ilog to optimize the metabolic concentrations (I think?) per given network.
    • This included the ability to synthesize all required precursor biomolecules; see supplementary information.
    • ‘’’“Viable” is highly permissive -- non-zero biomolecule concentration using FBA and linear programming. ‘’’
    • Genomic distances = hamming distance between binary vectors, where 1 = enzyme / reaction possible; 0 = mutated off; 0 = identical genotype, 1 = completely different genotype.
  • Between pairs of viable genetic-metabolic networks, only a minority (30 - 40%) of reactions are essential,
    • Which naturally increases with increasing carbon source diversity:
    • When they go back an examine networks that can sustain life on any of (up to) 60 carbon sources, and again measure the distance from the original E. Coli genome, they find this added robustness does not significantly constrain network architecture.

Summary thoughts: This is a highly interesting study, insofar that the authors show substantial support for their hypotheses that phenotypes can be explored through random-walk non-lethal mutations of the genotype, and this is somewhat invariant to the source of carbon for known biochemical reactions. What gives me pause is the use of linear programming / optimization when setting the relative concentrations of biomolecules, and the permissive criteria for accepting these networks; real life (I would imagine) is far more constrained. Relative and absolute concentrations matter.

Still, the study does reflect some robustness. I suggest that a good control would be to ‘fuzz’ the list of available reactions based on statistical criteria, and see if the results still hold. Then, go back and make the reactions un-biological or less networked, and see if this destroys the measured degrees of robustness.

{1389}
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ref: -0 tags: photoacoustic tomography mouse imaging q-switched laser date: 05-11-2017 05:23 gmt revision:1 [0] [head]

Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution

  • Used Q-switched Nd:YAG and Ti:Sapphire lasers to illuminate mice axially (from the top, through a diffuser and conical lens), exciting the photoacuostic effect, from which they were able to image at 125um resolution a full slice of the mouse.
    • I'm surprised at their mode of illumination -- how do they eliminate the out-of-plane photoacoustic effect?
  • Images look low contrast, but structures, e.g. cortical vasculature, are visible.
  • Can image at the rep rate of the laser (50 Hz), and thereby record cardiac and pulmonary rhythms.
  • Suggest that the photoacoustic effect can be used to image brain activity, but spatial and temporal resolution are limited.

{1390}
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ref: -0 tags: photoacoustic tomography mouse imaging q-switched laser date: 05-11-2017 05:21 gmt revision:0 [head]

Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution

  • Used Q-switched Nd:YAG and Ti:Sapphire lasers to illuminate mice axially, exciting the photoacuostic effect, from which they were able to image at 125um resolution a full slice of the mouse.
  • Images look low contrast, but structures, e.g. cortical vasculature, are visible.
  • Can image at the rep rate of the laser (50 Hz), and thereby record cardiac and pulmonary rhythms.
  • Suggest that the photoacoustic effect can be used to image brain activity, but spatial and temporal resolution are limited.

{1239}
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ref: -0 tags: electrode area review impedance date: 04-28-2017 17:55 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

Quick review of electrode area / impedance within m8ta:

  • {895} 500um^2
  • {311} 490um^2 nominal; 900k
  • {1040} 108um^2, plated from 5M to 1M.
  • Neuronexus: 177, 413um, 700um, and 1250um.
    • Suggest 177um for SUA, 413um for MUA.
    • Community consensus seems to be that these electrodes don't last as long, though.
    • Electroplating 177um^2 sites with PEDOT:PSS reduces impedance to 23k {1388}
  • {823} 122um^2 nominal
  • {736} 500um^2
  • {1027} (Utah) 1600um^2
    • Impedance: ~ 220K +-91K (in vivo -- large variance)
    • Blackrock site lists impedance @ 400k
  • SIrOF Utah array -- 3100um^2 (3.1e-5cm^2) -- large!
    • Impedance ~50K according to [www.blackrockmicro.com/userfiles/file/Microelectrode%20Arrays.pdf Blackrock product brochure].
  • PMID-20124668 (Utah again) 2000um^2, 125k Pt, 6k SIROF.
  • Neuropixel: 144um^2 acid-etched TiN
  • Carbon fiber: ~38 um^2, PEDOT:PSS or PEDOT:pTS started ~ 4M, plated down to ~ 130k initial, went up to 2M pSS, 840k pTS.