WO2004011084A1 - Dispositif de stimulation et d'enregistrement - Google Patents

Dispositif de stimulation et d'enregistrement Download PDF

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Publication number
WO2004011084A1
WO2004011084A1 PCT/GB2003/003197 GB0303197W WO2004011084A1 WO 2004011084 A1 WO2004011084 A1 WO 2004011084A1 GB 0303197 W GB0303197 W GB 0303197W WO 2004011084 A1 WO2004011084 A1 WO 2004011084A1
Authority
WO
WIPO (PCT)
Prior art keywords
tissue
sample
electrode
recording
electrodes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB2003/003197
Other languages
English (en)
Inventor
Edward Clarke Conley
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GE Healthcare UK Ltd
Original Assignee
Amersham Biosciences UK Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Amersham Biosciences UK Ltd filed Critical Amersham Biosciences UK Ltd
Priority to AU2003246958A priority Critical patent/AU2003246958A1/en
Priority to GB0501518A priority patent/GB2406913A/en
Publication of WO2004011084A1 publication Critical patent/WO2004011084A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0472—Structure-related aspects

Definitions

  • the present invention relates to devices of the type mentioned in the preambles of the independent claims for experiments on biological tissues or organs.
  • the present invention relates to an electrical stimulus-record device which through clamping onto pieces of excitable tissue or organs, provides a simple access method for measuring complex effects of drugs on different receptor and ion channel populations in a biological sample.
  • Figure 1 shows a schematic view from above of one embodiment of a device in accordance with the present invention
  • Figures 2a)-2c) show enlarged schematic plan, front respectively lateral views of the device from figure 1.
  • any references to orientations such as up, down, upper side, lower side or the like, are intended to be non-limiting and are only used to make it easier to understand the present invention and, unless otherwise stated, they refer to possible embodiments of devices in accordance with the present invention when positioned in the working configuration. Furthermore the skilled person will understand that the relative positions of the components can be reversed and/or rearranged while still remaining in the scope of the present claims.
  • FIG. 1 A first embodiment of a tissue clamping and testing device 1 in accordance with the present invention is shown schematically in fig. 1.
  • Device 1 is shown enlarged in figures 2a)-2c) which are, respectively, plan, front and lateral schematic views of device 1.
  • Device 1 comprises a gripping mechanism formed of a base plate 3 onto which a movable clamping frame 5 is pivotably mounted by means of a hinge 7.
  • Frame 5 comprises two parallel arms 9, each D mm (e.g. 10 mm) long, w mm wide (e.g. 1 mm) and t mm (e.g. 1mm thick), spaced a distance d (e.g. 2 mm) apart and each attached by a first end 11 to hinge 7.
  • Frame 5 is pivotable from a working position, in which it is substantially parallel to the surface of base plate 3 with the arms 9 in a tissue clamping position over a tissue placement region 13 (and in which working position it is intended that in use it would be in clamping contact with the tissue being sampled), to a non-working position where arms 9 are not in a tissue clamping position over tissue placement region 13 (and in which non-working position it is intended that in use it would not be in clamping contact with the tissue being sampled) .
  • the second end 15 of each arm 9 is joined to a buffer chamber 17 mounted on, and extending between, arms 9.
  • Buffer chamber 17 comprises a tubular open-ended bath portion 19 attached to the under surface of the periphery of a central hole 21 formed in a fiat plate 23 which is mounted on the upper surface of second end of arms 9. Bath portion 19 protrudes a distance p mm (e.g. 1 mm) which is sufficient to ensure that when it is clamped into contact with a piece of tissue its periphery forms a seal against the piece of tissue.
  • a recording electrode 25 is positionable in bath portion 19. Recording electrode 25 is sufficiently long enough to penetrate sufficiently deep enough into the tissue so as to ensure electrical contact with living cells inside the tissue and is connectable to a recording means such as a computer (not shown).
  • a bath electrode 26 positioned inside buffer chamber 17 and connectable to the recording means completes the recording circuit with the recording electrode. Buffer chamber 17 may contain a buffer liquid
  • the buffer liquid 16 which prevents the tissue from drying out and the buffer liquid may be supplied with, or exchanged for, other liquids such as nutrient liquids or drugs or drug candidates or the like.
  • the same or a different liquid 18 may be provided in the space between the buffer chamber 17 and the frame arms 9.
  • each arm 9 is provided with a plurality of electrode teeth 29 resp. 29' which project down out of underside 27.
  • electrode teeth 29, 29' are made of insulating material and have conducting tips that are sufficiently long enough to penetrate sufficiently deep enough into the tissue so as to ensure electrical contact with responsive cells inside the tissue.
  • the teeth penetrate to a depth of from 0.05 mm to 2.0 mm, more preferably from 0.2 mm to 1.0 mm.
  • Electrode teeth 29, 29' are connectable to a power supply (not shown) which can be controlled, for example by a computer, to provide stimulating pulses to the piece of tissue.
  • Frame 3 is preferably biased into the working position e.g. by biasing means such as a spring (not shown), and/or is provided with locking means (not shown) for releasably locking it in the working position.
  • biasing means such as a spring (not shown)
  • locking means not shown
  • a method of using device 1 to hold a piece of tissue comprises the following steps: 1) frame 3 is moved to a non- working position;
  • tissue receiving portion 33 2) a piece of tissue 35 is placed on tissue receiving portion 33; 3) frame 3 is moved to the working position so that electrode teeth 29, 29' and recording electrode 25 penetrate into piece of tissue 35, thereby simultaneously clamping the tissue into place and establishing electrical contact with it.
  • a method of experimenting on a piece of tissue may comprise the further steps of:
  • device 1 is able to produce a rapidly-actuating, but strong and reliable physical clamp of the tissue being tested which serves to overcome the confounding effects of excitation- induced contraction.
  • the frame 3 also enables good electrical contact for delivery of stimuli at the periphery of the tissue 35, and at the same time the central region of the tissue is automatically punctured by the recording electrode 25.
  • Figures 3a) and 3b) show a second embodiment of the present invention in which a simple gripping mechanism is provided with many recording electrodes that can be reliably and easily inserted at the same time by a device 41 provided with an array of recording electrodes 55.
  • the device is further provided with drug introducing means to introduce drug-containing solutions either to a surface of the tissue 35.
  • Array 43 comprises a quadratic planar substrate 45 with one face 47 intended to be brought into contact with a piece of tissue 35. Face 47 may be provided with a central quadratic grid 49 of microgrooves 51 which surround a plurality of electrode islands 53.
  • Each electrode island 53 is in the shape of a square protuberance and is provided with a central recording electrode 55 which projects a short distance h (e.g.
  • the electrodes 55 extend though substrate 45, project out of the second face 57 of substrate and are connected to a data buss (not shown). Each electrode is surrounded by an insulating electrode sheath 59 which during use seals against the piece of tissue and prevents short-circuit currents between electrodes.
  • Two opposite edges of substrate 45 are provided with longitudinal clamping electrodes 61 which project a short distance k (e.g.
  • Microgrooves 51 may be used to allow drugs and other fluids to be introduced and to flow across the substrate 45 and therefore are made deep enough to avoid then being filled with tissue when the substrate 45 is clamped against a piece of tissue. Drugs and fluids may be introduced to the microgrooves via an inlet hole 63 which extends through substrate 45 at one corner of the grid 49, and they may be removed from the microgrooves via an outlet hole 65 which extends through substrate 45 at the opposite corner of the grid 49.
  • a clamping frame 71 (shown schematically by dashed lines) is able to be position over the face 47 of the substrate and can be moved towards the face 47 in order to force the electrodes to penetrate tissue 35.
  • a device in accordance with the present invention enables continuous delivery of electrical stimuli and recording of responses via electrodes while dipping the device 1, 41 into different drug-containing or wash solutions, a procedure that can be carried out by an operator or robot arm or laboratory transport system.
  • the ends of the electrodes are made sharp enough to penetrate solid tissue (e.g. with pointed (conical) tips).
  • Embodiments of the present invention may use solid-state stimulus-recording electrode pairs.
  • the arrangement and spacing of the stimulus electrode(s) and recording electrode(s) together with the appropriate insulating barriers are defined to maximise the number of simultaneous output signals (or facilitate their sequential recording) while minimising cross-talk between adjacent electrode pairs.
  • Each electrode pair in an array may be programmable for sequential stimulus and recording, as commonly practised in the field, on sample tissues sliced and placed in a physical clamp, which is an intrinsic part of the electrode device.
  • the individual stimulus-record (S-R) electrode pairs may be packed closely together but separated by insulation to prevent cross-talk.
  • Such devices in accordance with the present invention to perform experiments on a complete organ, for example a mouse, rat or rabbit heart.
  • Such devices for performing experiments on such organs are preferably provided with means for keeping the organ alive during the experiment as well as means for perfusing the organ with, preferably oxygenated, drug-containing solutions.
  • Devices in accordance with the present invention which clamp on to a tissue or organ sample while rendering it stimulatable and recordable, bring improvements (viz. rapidity, quality of device-to-tissue seal/access, consistency of recording, simplicity) over traditional approaches and enable presentation of the 'captured' tissue or organ to drug-containing and wash solutions in hitherto difficult formats (e.g. the tissue or organ and the stimulus-record device as a unit may be inserted on to larger arrays or data buss devices for batch processing/ recording and/or dipped in solutions controlled by a robot).

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

L'invention concerne un dispositif servant à stimuler un échantillon biologique, caractérisé en ce qu'il comprend des moyens de serrage servant à serrer un échantillon, ainsi que des électrodes servant à stimuler ledit échantillon, lesdits moyens de serrage et lesdites électrodes étant disposés de telle sorte que lorsque l'échantillon biologique est serré à l'aide des moyens de serrage, les électrodes pénètrent sensiblement simultanément dans l'échantillon.
PCT/GB2003/003197 2002-07-30 2003-07-28 Dispositif de stimulation et d'enregistrement Ceased WO2004011084A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003246958A AU2003246958A1 (en) 2002-07-30 2003-07-28 Stimulating and recording device
GB0501518A GB2406913A (en) 2002-07-30 2003-07-28 Stimulating and recording device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0217554A GB0217554D0 (en) 2002-07-30 2002-07-30 Stimulating and recording device
GB0217554.5 2002-07-30

Publications (1)

Publication Number Publication Date
WO2004011084A1 true WO2004011084A1 (fr) 2004-02-05

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2003/003197 Ceased WO2004011084A1 (fr) 2002-07-30 2003-07-28 Dispositif de stimulation et d'enregistrement

Country Status (3)

Country Link
AU (1) AU2003246958A1 (fr)
GB (2) GB0217554D0 (fr)
WO (1) WO2004011084A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7067046B2 (en) 2000-08-04 2006-06-27 Essen Instruments, Inc. System for rapid chemical activation in high-throughput electrophysiological measurements
US7201836B2 (en) 1997-12-17 2007-04-10 Molecular Devices Corporation Multiaperture sample positioning and analysis system
US7244349B2 (en) 1997-12-17 2007-07-17 Molecular Devices Corporation Multiaperture sample positioning and analysis system
US7270730B2 (en) 2000-08-04 2007-09-18 Essen Instruments, Inc. High-throughput electrophysiological measurement system
CN104545905A (zh) * 2015-01-06 2015-04-29 朱志茹 安装有记录电极的实验架及实验方法
WO2017124108A3 (fr) * 2016-01-15 2018-07-26 The United States Government As Represented By The Department Of Veterans Affairs Dispositifs et procédés pour des mesures de tension et applications de ceux-ci

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5759846A (en) * 1995-04-12 1998-06-02 Chemodyne S.A. Device for the study of organotypic cultures and its uses in electrophysiology and biochemistry
US6030384A (en) * 1998-05-01 2000-02-29 Nezhat; Camran Bipolar surgical instruments having focused electrical fields

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5759846A (en) * 1995-04-12 1998-06-02 Chemodyne S.A. Device for the study of organotypic cultures and its uses in electrophysiology and biochemistry
US6030384A (en) * 1998-05-01 2000-02-29 Nezhat; Camran Bipolar surgical instruments having focused electrical fields

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PISTER K S J: "MICROFABRICATED HINGES", SENSORS AND ACTUATORS A, ELSEVIER SEQUOIA S.A., LAUSANNE, CH, vol. A33, no. 3, 1 June 1992 (1992-06-01), pages 249 - 256, XP000297416, ISSN: 0924-4247 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7201836B2 (en) 1997-12-17 2007-04-10 Molecular Devices Corporation Multiaperture sample positioning and analysis system
US7244349B2 (en) 1997-12-17 2007-07-17 Molecular Devices Corporation Multiaperture sample positioning and analysis system
US7387715B2 (en) 1997-12-17 2008-06-17 Molecular Devices Corporation Sample positioning and analysis system
US7067046B2 (en) 2000-08-04 2006-06-27 Essen Instruments, Inc. System for rapid chemical activation in high-throughput electrophysiological measurements
US7270730B2 (en) 2000-08-04 2007-09-18 Essen Instruments, Inc. High-throughput electrophysiological measurement system
CN104545905A (zh) * 2015-01-06 2015-04-29 朱志茹 安装有记录电极的实验架及实验方法
CN104545905B (zh) * 2015-01-06 2017-09-15 朱志茹 安装有记录电极的实验架及实验方法
WO2017124108A3 (fr) * 2016-01-15 2018-07-26 The United States Government As Represented By The Department Of Veterans Affairs Dispositifs et procédés pour des mesures de tension et applications de ceux-ci
US10761001B2 (en) 2016-01-15 2020-09-01 Vanderbilt University Devices and methods for tension measurements and applications of same
US10876942B2 (en) * 2016-01-15 2020-12-29 Vanderbilt University Devices and methods for tension measurements and applications of same

Also Published As

Publication number Publication date
GB0501518D0 (en) 2005-03-02
GB2406913A (en) 2005-04-13
AU2003246958A1 (en) 2004-02-16
GB0217554D0 (en) 2002-09-11

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