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{1356}
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ref: -2016 tags: Kozai carbon fiber microelectrodes JNE PEDOT PSS pTS date: 04-27-2017 01:42 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-27705958 Chronic in vivo stability assessment of carbon fiber microelectrode arrays.

  • showed excellent recording characteristics and nearly zero glial scarring.
  • 6.4um carbon fiber + 800nm parylene-C = 8.4um.
    • Cytec Thoronel T-650 CF, Youngs modulus = 255 GPa, tensile strength = 4.28 GPa, PAN-based.
  • Everything protected with our wonderful phenol epoxy 353NDT, heat-cure.
  • Used two coating solutions:
    • Solution of 0.01 M 3,4-ethylenedioxythiophene (483028, Sigma-Aldrich, St. Louis, MO): 0.1 M sodium p-toluenesulfonate (152536, Sigma-Aldrich, St. Louis, MO).
      • pTS is not that dissimilar from it's alkyl cousin, SPS, {1353}. Likely a soapy chemical due to the opposed methyl and sulfonic acid group; benzine will take up less room in the polymer c.f. SDS & may lower the oxidation potential of EDOT.
      • Tosylates have been explored as a EDOT counterion : PMID-22383043 Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer microelectrodes for transmitter detection. and PEDOT-TMA
    • Solution was composed of 0.01 M 3,4-ethylene-dioxythiophene (483028, Sigma-Aldrich, St. Louis, MO):0.1 M polystyrene sulfonate (m.w. 70.000, 222271000, Acros, NJ).
    • For each solution the electrodeposition was carried out by applying 100 pA/channel for 600 s to form a layer of poly(3,4-ethylenedioxythiophene):sodium p-toluenesulfonate (PEDOT:pTS) or poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS).
      • Weird, would use voltage control here..
  • According to works by Green et al [45] and Hukins et al [46], equation (1) can be used to determine the aging time that
the fibers have undergone: t 37=t TQ10 T37)/10 where t 37 is the simulated aging time at 37 °C, t T is the amount of real time that the samples have been kept at the elevated temperature, T , and Q10 is an aging factor that is equal to 2, according to ASTM guidelines for polymer aging [47].
  • Show > 2MOhm impedance of the small-area electrodes. At the aging endpoint, PEDOT:pTS had about half the impedance of PEDOT:PSS.
    • 4M PSS, 7M pTS, both plated down to ~ 130k initial, went up to 2M pSS, 840k pTS.
  • Recording capability quite stellar
  • Likewise for the glial response.

{1381}
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ref: -0 tags: glassy carbon SU-8 pyrolysis CEC microelectrode stimulation stability platinum PEDOT date: 02-17-2017 00:05 gmt revision:2 [1] [0] [head]

A novel pattern transfer technique for mounting glassy carbon microelectrodes on polymeric flexible substrates

  • Use inert-atmosphere pyrolysis @ 900 - 1000 C of 20um SU-8 (which is aromatic) on a thermal oxide wafer.
  • Followed by spin & cure of PI.
  • Demonstrate strong carbonyl bonding of the glassy carbon with mechanical and FTIR testing.
  • Use of photosensitive PI allows through-vias to connect Cr/Au conductive traces.

PMID-28084398 Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

  • Use EIS to show superior charge-injection properties + stability of glassy carbon electrodes vs. Pt electrodes.
    • GC lasted > 5e6 pulses; Pt electrodes delaminated after 1e6 pulses.
    • Hydrogen bonding (above) clearly superior than neat PI-Pt interface
  • GC electrodes were, true to their name, glassy and much smoother than the platinum electrodes.
  • Further reduced impedance with PEDOT-PSS coating.
    • PEDOT-PSS coating on glassy carbon was, in their hands, far more stable than PEDOT-PSS on platinum.
  • All devices, GC, PEDOT:PSS, and Pt, had similar biocompatibility in their assay (figure 7)

{1281}
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ref: -0 tags: microelectrode patents date: 05-02-2014 00:07 gmt revision:1 [0] [head]

Various microelectrode patents:

Microelectronics:

{1237}
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ref: -0 tags: winslow Tresco 2010 BBB histology immune response microelectrodes date: 04-19-2013 23:25 gmt revision:0 [head]

PMID-19963267 Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.

  • Winslow BD, Tresco PA.
  • The spatial distribution of biomarkers associated with the foreign body response to insulated microwires placed in rat cerebral cortex was analyzed 2, 4, and 12 weeks after implantation using quantitative methods.
  • We found no evidence that reactive gliosis increases over time or that neuronal loss is progressive, we did find evidence of persistent inflammation and enhanced BBB permeability at the electrode brain tissue interface that extended over the 3 month indwelling period and that exhibited more animal to animal variability at 3 months than at 2 and 4 weeks.

{999}
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ref: -0 tags: microelectrodes original metal pipette glass recording MEA date: 01-31-2013 19:46 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-4065599 (pdf) Comments on Microelectrodes

  • The amplifiers themselves, even back in 1950's, posed no problems -- low bandwidth. All that is required is low noise and high input impedance.
  • KCl Glass electrodes are LPF (10M resistive + 10pf parasitic capacitance); metal HPF (capacitive).
    • The fluid tip will not see external triphasic spikes of vertebrate axons above the noise level.
  • Metal probe the most useful.
  • Pt electrode in CSF behaves like a capacitor at low voltage across a broad frequency range. CSF has compounds that retard oxidation; impedance is more resistive with physiological saline.
  • Noise voltage generated by a metal electrode best specified by equivalent noise resistance at room temperature, E rmsnoise=4kTR nδF R_n should equal the real part of the electrode impedance at the same frequency.
  • Much of electrochemistry: solid AgCl diffuses away from an electrode tip with great speed and can hardly be continuously formed with an imposed current. Silver forms extremely stable complexes with organic molecules having attached amino and sulfhydril groups which occur in plenty where the electrode damages the tissue. Finally, the reduction-oxidation potential of axoplasm is low enough to reduce methylene blue, which places it below hydrogen. AgCl and HgCl are reduced.
  • The external current of nerve fibers is the second derivative of the traveling spike, the familiar triphasic (??) transient.
  • Svaetichin [1] and Dowben and Rose [3] plated with Platinum black. This increases the surface area.
    • Very quickly it burns onto itself a shell of very adherent stuff. It is kept from intimate contact with the tissue around it by a shell.
    • We found that if we add gelatin to the chloroplatinic acid bath from which we plate the Pt, the ball is not only made adherent to the tip but is, in a sense, prepoisoned and does not burn a shell into itself.
  • glass insulation using woods metal (which melts at a very low temperature). Platinum ball was plated onto 2-3um pipette tip. 3um gelatinized platinum black ball, impedance 100kOhm at 1kHz.
    • Highly capacitive probe: can be biased to 1 volt by a polarizing current of 1e-10 amp. (0.1nA).
  • Getting KCl solution into 1um pipettes is quite hard! They advise vacuum boiling to remove the air bubbles.
  • Humble authors, informative paper.

____References____

' ''' ()

{823}
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ref: Kruger-2010.05 tags: microelectrode array nichrome 7 years rhesus electrophysiology MEA Kruger oblique inverted date: 01-29-2013 07:54 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-20577628[0] Seven years of recording from monkey cortex with a chronically implanted multiple electrode.

  • Seven years!! good recordings the whole time, too. As they say, this is a clinically realistic time period. Have they solved the problem?
  • Used 12.5um Ni-Cr-Al wire insulated with 3um of polymide.
    • Wires were then glued to an 8x8 connector block using conductive epoxy.
    • Glued the bundle together with a solution of plexiglas in dichloroethane.
    • Then introduced the 0.3mm bundle into a j-shaped cannula. This allowed them to approach the gray matter inverted, from below (the white matter).
    • implanted 64 ch array into ventral premotor cortex (arm representation?).
  • No apparent degradation of recording quality over that time.
  • Had some serious problems with the quality of their connector.
    • They recommend: "Rather, the contacts on the head should be made from noble metals and be flat or shallowly hollow, so that they can be easily cleaned, and no male contacts can break."
    • Really need to amplify and multiplex prior connector (imho).
  • Claim that them managed to record from two neurons on one channel for nearly 7 years (ch 54).
  • They cite us, but only to indicate that we recommend slow penetration of the brain. They agree with our results that lowering of individual electrodes is better than all at once.

____References____

[0] Kruger J, Caruana F, Volta RD, Rizzolatti G, Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode.Front Neuroengineering 3 Issue 6 (2010 May 28)

{946}
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ref: Salcman-1976.01 tags: Salcman electrodes recording chronic microelectrode array MEA original parylene date: 01-28-2013 22:18 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-1256090[0] A new chronic recording intracortical microelectrode

  • maintain that tethering is the rational way to go: it "re-establishes the normal biomechanics of the intact cranial vault". (Salcman 1972, 1973) {1010}
    • have model of electrode tip motion in response to brain-skull displacements (Goldstein and Salcman 1973) {1011}
      • Electrode would have a tip displacement of about 5um in response to a 1mm displacement of the electrode's point of entry into the skull.
      • Exponential dependence on recording amplitude and distance (Rall, 1962). Gradient: 7.5uv/um; movements of more than 1-2um can radically alter the recordnig shape.
      • Probably our electrodes work because the dura & gliosis becomes firmly attached to the electrode shafts.
    • not really an array so much as a number (10-12) of single-unit electrodes.
  • Details the process of parylene-C deposition, electrode microwelding, etc. Pretty cool stuff -- what has happened to this technology?
  • Each bubble is glued with cyanocrylate to the pia. (they too question the safety of this).
  • arrays can be manually inserted via forceps.
  • 25um iridium wire electroplated in 1-2um of gold
    • then electo-etched until the desired tip geometry is achieved, 1-3um diameter
    • and vacuum coated in 3um of parylene-C.
    • Impedance 1-2M with a 1kHz sine wave at 10nA. Impedance is inversely related to the frequency of the test current, phase angle of 70-80deg.
      • Ref Robinson, 1968.
    • We must emphasize the extreme sensitivity of electrode measurements to the test conditions. Measured values of Z e are usually increased 1-3M when the electrode has been stored away for a few days. Removing the electrode from the test bath for a few minutes in air can lead to equally large increases when the electrode is tested upon remersion. [...] might be oxide.
    • Pinholes are the usual failure mechanism (KD Wise 2004), {149}; parylene is 'pinhole-free'.
  • The connecting 25um Au lead is very flexible and imposes little stress on the iridium electrode.
    • Connecting wire coated in 12um of parylene C
    • Would prefer even finer wire, 12um.
  • Perspex window over the craniotomy; had a vent in this window which they could open.
  • Opening the vent would cause the brain to pulse, moving the electrodes through the cortex and changing neural activity.
  • Size of an electrode is limited by ability to introduce it into the brain.
    • Electrode must be introduced through the pia; as the pial vessels supply the cortex (or drain the cortex).
    • For their electrodes, P crit=0.9g ; the force necessary to penetrate the pia is 0.05 - 0.2g.
  • pure iridium is stiffer than Pt-Ir by a factor of 3 or so. (521 G N/m^2 = 521 GPa, higher than tungsten, which is 400 Gpa)
    • Pure iridium is apparently the stiffest metallic element ref
  • Interesting: "Once again we are impressed by the fact that passive recording electrodes exhibit drops in impedance in the living system which they never show on in vitro testing in protein solutions at 37C.
    • Between 40 and 50 days, a slow downward trend becomes noticeable; this trend continues for the life of the animal and asymptotically approaches values below 500k. Electrodes still record.
    • See {999}
    • Surmise that pure iridium electrodes have a different metal-electrolyte interface than more conventional metals (Pl and W).
  • Mention that the ultimate purpose is for a neural prosthesis.
    • Their then use was for recordings from M1 in monkeys and V1 from cats. (Schmidt, Bak, McIntosh 1974)
  • Ref Wise et al {1012}.

____References____

[0] Salcman M, Bak MJ, A new chronic recording intracortical microelectrode.Med Biol Eng 14:1, 42-50 (1976 Jan)

{1010}
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ref: Salcman-1973.07 tags: Salcman MEA microelectrodes chronic recording glass cyanocrylate date: 01-28-2013 02:37 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-4120641 (pdf) 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)

{898}
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ref: Ward-2009.07 tags: microelectrode arrays immune response recording MEA Purdue date: 01-28-2013 01:52 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19486899[0] Toward a comparison of microelectrodes for acute and chronic recordings.

  • Good research, paper well written.
  • Results suggest significant variability within and between microelectrode types with no clearly superior array (from the abstract).
  • As Miguel mantains, "Much of the new technology, however, does not supersede traditional microwire technology in its ability to evade a host immune response".
  • Initial implantation wound initiates a cascade of immune responses which culminates in a sheath of microglia, astrocytes, various ectracellular matrix constituents, and macrophages.
    • Decent citation list -- many people have been working on MEAs.
  • Fibrous encapusulation of the electrode is much less conductive than healthy nervous tissue, hence impedance measurements can be used to track tissue response.
  • Used Osort to sort the recorded neurons.
  • "Despite differing implant locations, and thus potentially differing levels of background neural activity, and differing scarring responses, which relates to the level of thermal noise in the observed signal (Ludwig et al., 2006), no significant SNR differences were observed among the MEA types for the duration of the study."
  • SNR trends did not seem to relate to site impedance trends over the 31-day period, and by inference, the extent of tissue encapsulation and neuronal density loss.
    • SNR is likely controlled by background neural noise, not thermal noise (which would be linked to impedance).
  • Electrodes with lower impedance generally recorded units from more sites than arrays with higher impedance.

____References____

[0] Ward MP, Rajdev P, Ellison C, Irazoqui PP, Toward a comparison of microelectrodes for acute and chronic recordings.Brain Res 1282no Issue 183-200 (2009 Jul 28)

{897}
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ref: Harris-2011.08 tags: microelectrodes nanocomposite immune response glia recording MEA date: 01-27-2013 22:19 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21654037[0] In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes

  • J P Harris, A E Hess, S J Rowan, C Weder, C A Zorman, D J Tyler and J R Capadona Case Western University.
  • Simple idea: electrodes should be rigid enough to penetrate the brain, yet soft enough to not damage it once implanted.
  • Many studies have shown that shear stress around a microelectrode shaft causes neural die-off and glial response.
  • You can only record from neurons if they are < 100um from the electrode tip.
  • Nanocomposite material is inspired by sea cucumber skin.
    • Our materials exhibit this behaviour by mimicking the architecture and proposed switching mechanism at play in the sea cucumber dermis by utilizing a polymer NC consisting of a controllable structural scaffold of rigid cellulose nanofibres embedded within a soft polymeric matrix. When the nanofibres percolate, they interact with each other through hydrogen bonding and form a nanofibre network that becomes the load-bearing element, leading to a high overall stiffness of the NC. When combined with a polymer system which additionally undergoes a phase transition at physiologically relevant temperatures, a contrast of over two orders of magnitude for the tensile elastic modulus is exhibited.
  • Probes were 200um wide, 100um thick, and had a point sharpened to 45deg.
  • Buckle force testing was done on 53um thick, 125um wide probes sharpened to a 30deg point.
  • Penetration stress through the rat pia is 1.2e7 dynes/cm^2 for a Si probe 40um thick and 80um wide.
  • See also {1198}

____References____

[0] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)

{737}
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ref: Biran-2005.09 tags: microelectrode Michigan probe glia tissue response electrode immune histology MEA Biran date: 01-24-2013 20:49 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • See also {1190} (wow, I'm redundant!)
  • Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.
    • CD68 = ED1 is a marker for microglia and other macrophages. (wikipedia article is informative).
    • GFAP = glial fibrillary acidic protein, marker for astrocytes.
  • Recording failure is caused by chronic inflammation (mostly activated microglia) at the microelectrode brain tissue interface.
  • Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?
  • What did they coat the silicon probes in?
  • Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.
  • Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.
    • Well then, how do you make the electrodes biochemically / biologically 'invisible'?
    • Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.
  • Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.
  • Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.

____References____

[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)

{1024}
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ref: COLLIAS-1957.05 tags: histology microelectrode vasulature date: 01-23-2013 23:56 gmt revision:4 [3] [2] [1] [0] [head]

PMID-13429398[0] Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.

  • Quite a good and overcomplete / long article -- fully describes their result of implanting bundles of 0.005" varnished steel wires into the brains of cats.
    • Saw hemorrhagic necrosis, necrosis from edema, and eventual encapsulation and collapse of capilaries around the chronic implant. All things that we still have to contend with.
  • From [1]: ... For single penetrating electrodes into cat cortex, Collias and Manuelidis noted and increase in hemorrhagic damage near electrode tracks of the cortex nearest the point of electrode entry into the pia.
  • They also reported that the damage appeared to be randomly distributed among the implants, which they attributed to differences in local vasculature.
  • The toxicity of certain metals, namely, platinum, platinum-8% tungsten, platinum-10% rhodium, platinum-10% iridium, platinum-10% nickel, platinized platinum, a gold-nickel-chromium alloy, a gold-palladium-rhodium alloy, a chromium-nickel-molybdenum alloy (Vitallium), stainless steel, silver, rhenium, and gold, was evaluated histologically following chronic implantation for 2 months in the brains of cats. Of the above metals, all but silver were found to be nontoxic. Boron was also evaluated and found to be nontoxic.

____References____

[0] COLLIAS JC, MANUELIDIS EE, Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.J Neurosurg 14:3, 302-28 (1957 May)
[1] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

{1189}
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ref: -0 tags: microelectrode array flexible PDMS via interconnect Georgia date: 01-04-2013 00:33 gmt revision:0 [head]

IEEE-6197244 (pdf) A PDMS-Based Integrated Stretchable Microelectrode Array (isMEA) for Neural and Muscular Surface Interfacing

  • Targeted at e.g. ECoG; in this paper, they look at cat muscle (epimyscial recording).
  • MEA is directly fabricated with a stretchable substrate, such as a thin PCB or ASIC, through via bonding for built-in packaging.

{1011}
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ref: Goldstein-1973.07 tags: Salcman microelectrodes bucking analysis stiffness youngs modulus mechanical MEA date: 01-04-2012 01:22 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-4120642 (pdf) Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes

____References____

Goldstein, Seth R. and Salcman, Michael Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 260 -269 (1973)

{1014}
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ref: GULD-1964.07 tags: platinum iridium microelectrode eltrolytic etching original date: 01-03-2012 19:05 gmt revision:2 [1] [0] [head]

PMID-14199966[0] A Glass-covered platinum microelectrode

  • Details the manufacture and testing of PT-IR (70/30) etched solder glass-coated microelectrodes.
  • Melt a bead of the glass on the top and gradually draw the bead downward, surrounded by the heater of a pipette drawing machine.

____References____

[0] GULD C, A GLASS-COVERED PLATINUM MICROELECTRODE.Med Electron Biol Eng 2no Issue 317-27 (1964 Jul)