U.S. patent application number 17/088048 was filed with the patent office on 2021-05-13 for combined stimulator and bipolar electrode assembly for mouse electroretinography (erg).
The applicant listed for this patent is Diagnosys LLC. Invention is credited to Marc Chabot, Bruce Doran.
Application Number | 20210137442 17/088048 |
Document ID | / |
Family ID | 1000005358590 |
Filed Date | 2021-05-13 |
![](/patent/app/20210137442/US20210137442A1-20210513\US20210137442A1-2021051)
United States Patent
Application |
20210137442 |
Kind Code |
A1 |
Doran; Bruce ; et
al. |
May 13, 2021 |
COMBINED STIMULATOR AND BIPOLAR ELECTRODE ASSEMBLY FOR MOUSE
ELECTRORETINOGRAPHY (ERG)
Abstract
Apparatus for evoking and sensing ophthalmic physiological
signals in an eye, the apparatus comprising: an elongated tubular
light pipe having a longitudinal axis, a distal end and a proximal
end, the distal end terminating in a spheroid recess; an active
electrode having a distal end and a proximal end, the active
electrode being mounted to the elongated tubular light pipe and
extending proximally along the elongated tubular light pipe so that
the distal end of the active electrode terminates at the spheroid
recess at the distal end of the elongated tubular light pipe; and a
reference electrode having a distal end and a proximal end, the
reference electrode being mounted to the elongated tubular light
pipe and extending proximally along the elongated tubular light
pipe so that the distal end of the reference electrode terminates
at the spheroid recess at the distal end of the elongated tubular
light pipe; wherein the distal end of the active electrode is
located closer to the longitudinal axis of the elongated tubular
light pipe than the distal end of the reference electrode.
Inventors: |
Doran; Bruce; (Lowell,
MA) ; Chabot; Marc; (Lowell, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Diagnosys LLC |
Lowell |
MA |
US |
|
|
Family ID: |
1000005358590 |
Appl. No.: |
17/088048 |
Filed: |
November 3, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15153286 |
May 12, 2016 |
10820824 |
|
|
17088048 |
|
|
|
|
62160503 |
May 12, 2015 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/398 20210101;
A61B 5/6821 20130101; A61B 2562/0209 20130101; A61B 2503/40
20130101; A61B 2562/182 20130101; A61B 2090/306 20160201; A61B
2503/42 20130101; A61B 3/0008 20130101 |
International
Class: |
A61B 5/398 20060101
A61B005/398; A61B 3/00 20060101 A61B003/00; A61B 5/00 20060101
A61B005/00 |
Claims
1. Apparatus for evoking and sensing ophthalmic physiological
signals in an eye, the apparatus comprising: an elongated tubular
light pipe having a longitudinal axis, a distal end and a proximal
end, the distal end terminating in a spheroid recess; an active
electrode having a distal end and a proximal end, the active
electrode being mounted to the elongated tubular light pipe and
extending proximally along the elongated tubular light pipe so that
the distal end of the active electrode terminates at the spheroid
recess at the distal end of the elongated tubular light pipe; and a
reference electrode having a distal end and a proximal end, the
reference electrode being mounted to the elongated tubular light
pipe and extending proximally along the elongated tubular light
pipe so that the distal end of the reference electrode terminates
at the spheroid recess at the distal end of the elongated tubular
light pipe; wherein the distal end of the active electrode is
located closer to the longitudinal axis of the elongated tubular
light pipe than the distal end of the reference electrode.
2. Apparatus according to claim 1 wherein the elongated tubular
light pipe comprises a configuration selected from the group
consisting of cylindrical, non-linear pseudo-cylindrical, and
another acceptable configuration.
3. Apparatus according to claim 1 wherein the spheroid recess is
sized to match the curvature of the eye of a mouse.
4. Apparatus according to claim 1 wherein the elongated tubular
light pipe comprises a light-transmissive material having a small
acceptance angle.
5. Apparatus according to claim 4 wherein the elongated tubular
light pipe comprises plexiglass.
6.-8. (canceled)
9. Apparatus according to claim 1 wherein the distal end of the
elongated tubular light pipe comprises a light diffuser.
10. Apparatus according to claim 1 wherein the distance between the
distal end of the active electrode and the distal end of the
reference electrode is substantially equal to the distance between
a portion of the eye which exhibits an evoked physiological signal
and a portion of the eye which exhibits a lesser evoked
physiological signal.
11. Apparatus according to claim 10 wherein the distance between
the distal end of the active electrode and the distal end of the
reference electrode is substantially equal to the distance between
the cornea and the perimeter of the eye.
12. Apparatus according to claim 1 wherein the distal end of the
active electrode terminates proximal to the distal end of the
reference electrode.
13. Apparatus according to claim 1 wherein at least one of the
active electrode and the reference electrode is formed out of at
least one from the group consisting of platinum, silver and
gold.
14. Apparatus according to claim 1 wherein the distal end of the
reference electrode is doubled over.
15. Apparatus according to claim 1 further comprising an enlarged
surface area conductor disposed at the distal end of the elongated
tubular light pipe and in electrical communication with the
reference electrode.
16. Apparatus according to claim 15 wherein the enlarged surface
area conductor comprises at least one from the group consisting of
a conductive foil and a conductive film.
17. Apparatus according to claim 1 further comprising at least one
light-transmissive element carried by the elongated tubular light
pipe.
18. Apparatus according to claim 17 wherein the at least
light-transmissive element comprises a light-transmissive sleeve
disposed coaxially over the elongated tubular light pipe.
19. Apparatus according to claim 18 wherein the at least
light-transmissive element is constructed so as to transmit red
light.
20. Apparatus according to claim 1 further comprising a light
source for introducing light into the proximal end of the elongated
tubular light pipe.
21. Apparatus according to claim 1 wherein the light source is
adapted to emit light configured to evoke ophthalmic physiological
signals in an eye.
22. Apparatus according to claim 21 wherein the light source
comprises LEDs.
23. Apparatus according to claim 22 wherein the LEDs comprise at
least one red LED, at least one green LED and at least one blue
LED.
24. Apparatus according to claim 1 further comprising an
electromagnetic interference (EMI) shield.
25. Apparatus according to claim 24 wherein the electromagnetic
interference (EMI) shield comprises a wire mesh.
26. Apparatus according to claim 1 further comprising an adjustable
mount for supporting the elongated tubular light pipe.
27. Apparatus according to claim 26 wherein the adjustable mount
comprises a magnetic ball mount.
28. Apparatus according to claim 1 further comprising additional
apparatus for evoking and sensing ophthalmic physiological signals
in a second eye, the additional apparatus comprising: a second
elongated tubular light pipe having a longitudinal axis, a distal
end and a proximal end, the distal end terminating in a spheroid
recess; a second active electrode having a distal end and a
proximal end, the second active electrode being mounted to the
second elongated tubular light pipe and extending proximally along
the second elongated tubular light pipe so that the distal end of
the second active electrode terminates at the spheroid recess at
the distal end of the second elongated tubular light pipe; and a
second reference electrode having a distal end and a proximal end,
the second reference electrode being mounted to the second
elongated tubular light pipe and extending proximally along the
second elongated tubular light pipe so that the distal end of the
second reference electrode terminates at the spheroid recess at the
distal end of the second elongated tubular light pipe; wherein the
distal end of the second active electrode is located closer to the
longitudinal axis of the second elongated tubular light pipe than
the distal end of the second reference electrode; and further
wherein the first apparatus is configured to be deployable in
contact with one eye of a test subject and the second apparatus is
configured to be deployable in contact with the other eye of a test
subject.
29. Apparatus according to claim 28 wherein the first active
electrode provides one input to a differential amplifier, and the
second active electrode provides the other input to a differential
amplifier.
30. Apparatus according to claim 28 wherein the first reference
electrode provides one input to a differential amplifier, and the
second reference electrode provides the other input to the
differential amplifier.
31. A method for evoking and sensing ophthalmic physiological
signals in an eye, the method comprising: providing apparatus
comprising: an elongated tubular light pipe having a longitudinal
axis, a distal end and a proximal end, the distal end terminating
in a spheroid recess; an active electrode having a distal end and a
proximal end, the active electrode being mounted to the elongated
tubular light pipe and extending proximally along the elongated
tubular light pipe so that the distal end of the active electrode
terminates at the spheroid recess at the distal end of the
elongated tubular light pipe; and a reference electrode having a
distal end and a proximal end, the reference electrode being
mounted to the elongated tubular light pipe and extending
proximally along the elongated tubular light pipe so that the
distal end of the reference electrode terminates at the spheroid
recess at the distal end of the elongated tubular light pipe;
wherein the distal end of the active electrode is located closer to
the longitudinal axis of the elongated tubular light pipe than the
distal end of the reference electrode; positioning the elongated
tubular light pipe against the eye of a test subject; and
introducing light into the proximal end of the elongated tubular
light pipe.
Description
REFERENCE TO PENDING PRIOR PATENT APPLICATION
[0001] This patent application claims benefit of pending prior U.S.
Provisional Patent Application Ser. No. 62/160,503, filed May 12,
2015 by Diagnosys LLC and Bruce Doran et al. for COMBINED
STIMULATOR AND BIPOLAR ELECTRODE ASSEMBLY FOR MOUSE
ELECTRORETINOGRAPHY (ERG) (Attorney's Docket No. DIAGNOSYS-1 PROV),
which patent application is hereby incorporated herein by
reference.
FIELD OF THE INVENTION
[0002] This invention relates generally to apparatus and methods
for the assessment of electrophysiological signals, and more
particularly to apparatus and methods for the assessment of
ophthalmic physiological signals.
BACKGROUND OF THE INVENTION
[0003] Full-field ophthalmic electrophysiology generally involves
flashing a light from a large "bowl" into the eye of the subject,
and then measuring the response from the retina of the subject
using electrodes, i.e., an active electrode which contacts the eye
of the subject and other electrodes (reference and ground
electrodes) which contact other portions of the subject. This
procedure is sometimes referred to as electroretinography
(ERG).
[0004] Clinically, the hardest part of performing ophthalmic
electrophysiology is properly connecting the electrodes to the
subject and, more particularly, properly connecting the active
electrode to the eye of the subject.
[0005] In some cases the ophthalmic electrophysiology must be
conducted on humans. In other cases the ophthalmic
electrophysiology must be conducted on small rodents of the sort
commonly used in laboratory experiments, e.g., mice and rats (for
the purposes of the present invention, such animals will generally
be referred to herein as "mice", however, it should be appreciated
that such term is meant to be exemplary and not limiting). It will
be appreciated that conducting electrophysiology on mice can
present issues which may be different from the issues which might
arise when conducting electrophysiology on humans.
[0006] In present configurations for performing ophthalmic
electrophysiology on mice, e.g., with an ERG dome such as that
offered by Diagnosys LLC of Lowell, Mass., the anesthetized mouse
is placed on a heated platform that maintains its body temperature
during the test. At least three electrodes must be attached to the
mouse: (i) a ground electrode; (ii) a reference electrode; and
(iii) a corneal (active) electrode. In best current practice, all
three electrodes are made out of platinum or silver/silver chloride
and consist of two needles and a wire. One of the needles is used
as a ground electrode and is easy to attach to the mouse because
its position is not critical--anywhere in the haunch or tail of the
mouse will do. Placement of the other two electrodes (i.e., the
reference and active electrodes) requires much more care. The
remaining needle electrode is the reference electrode. It must be
inserted very precisely into the mouse, either at the midline of
the scalp, in the mouth, or in the cheek. Mispositioning of the
reference electrode will cause imbalances in the readings between
the two eyes of the mouse. The last electrode, the wire electrode,
is the corneal (active) electrode. It too must be placed in just
the right position on the eye in order to avoid biasing the
recording: too close to the center of the eye and the wire will
block light; too far to the periphery of the eye and the wire will
record lower voltages than if placed nearer to the center of the
eye. If both eyes of the animal are to be tested, a second corneal
wire must be placed in a homologous position to the first corneal
wire. An added complication is that, usually, all this must be done
in a room only dimly illuminated by deep red light.
[0007] After the three electrodes have been placed on the mouse,
the ERG dome is either moved into position over the mouse or the
platform supporting the mouse is moved into the dome. Either
movement may disturb the electrodes placed on the mouse, which
would then require that the electrodes be repositioned. Since the
mouse is hidden by the dome, it sometimes wakes up and escapes
under cover of darkness.
[0008] FIG. 1 shows the current Diagnosys mouse ERG dome platform
in its open position.
[0009] FIG. 2 shows the same Diagnosys mouse ERG dome platform in
its closed position.
[0010] It will be appreciated that conducting ophthalmic
electrophysiology on a mouse is time-consuming and requires
personnel with special skills. For this reason, ophthalmic
electrophysiology is sometimes not performed on mice even where the
results of performing ophthalmic electrophysiology could be
beneficial. By way of example but not limitation, NIH has an
impending campaign to phenotype more than 300,000 mutated mice.
Among other things, the mice are being tested for deficits
analogous to human eye disease. Although some of these deficits can
only be detected using ophthalmic electrophysiology,
electrophysiology was initially excluded from the testing protocols
because existing techniques for performing ophthalmic
electrophysiology on mice are too time-consuming and require
personnel with rare skills.
[0011] Ophthalmic electrophysiology would be significantly easier
to perform on mice if there were a way to rapidly and automatically
position the active and reference electrodes on the mouse. There is
an existing device (a "contact lens bipolar corneal electrode")
that does this effectively for humans, but in its present state the
contact lens bipolar corneal electrode is not practical for
widespread use with mice.
[0012] More particularly, a contact lens bipolar corneal electrode
consists of a lid-retracting speculum with a reference electrode
embedded in its outer circumference. A contact lens ringed by the
corneal electrode is suspended by a spring from the inner part of
the speculum. Since both active and reference electrodes are built
into the device, the two electrodes occupy the same position on
every eye (which is easily adjusted during manufacture to be at the
correct position on the eye of the subject). As a result, the
contact lens bipolar corneal electrode provides highly reliable
positioning of the active and reference electrodes, and hence
provides highly reliable results. A further advantage of the
contact lens bipolar corneal electrode is that both electrodes
(active and reference) touch the tear film, making excellent
electrical contact with the subject without special
preparation.
[0013] FIG. 3 shows a human contact lens bipolar corneal electrode
which was introduced by Diagnosys in 1986.
[0014] FIG. 4 shows another human contact lens bipolar corneal
electrode sold by Hansen Ophthalmic Development Laboratories of
Coralville, Iowa (hereinafter "Hansen Labs").
[0015] As noted above, human contact lens bipolar corneal
electrodes work effectively, but mouse contact lens bipolar corneal
electrodes are impractical for widespread use with mice. More
particularly, a mouse contact lens bipolar corneal electrode is
available from Hansen Labs, but the mouse contact lens bipolar
corneal electrode is impractically delicate, expensive, and hard to
make. The basic problem with the mouse contact lens bipolar corneal
electrode sold by Hansen Labs is that the manufacturer does not
know how its customers are going to use the lens--they may have an
application that needs the animal to view an image--and so the
manufacturer has to start by wrapping a corneal electrode around an
optically "good", zero-power mouse contact lens, and this is a
challenging task.
[0016] Another problem with mouse contact lens bipolar corneal
electrodes is that, if anything, they slow the testing process down
rather than speed it up. The mouse contact lens bipolar corneal
electrodes are so delicate and sensitive that they require great
care and skill in order to place them properly on the eye of the
mouse--by way of example but not limitation, it is very easy to
accidentally cover the mouse contact lens bipolar corneal
electrodes with saline solution which shorts them out, and they
often break during handling. In any case, mouse contact lens
bipolar corneal electrodes are so hard to make that they are
usually now offered only in monopolar versions, which means that
the problem of placing the reference electrode on the mouse is
still left to the user. The only real advantage of current mouse
contact lens bipolar corneal electrodes over current wire
electrodes is that the mouse contact lens bipolar corneal
electrodes cover the cornea and prevent the formation of cataracts
in the mouse due to drying.
[0017] FIG. 5 shows the mouse contact lens bipolar corneal
electrode sold by Hansen Labs.
[0018] Thus there is a need for a new and improved approach for
quickly and easily performing ophthalmic electrophysiology on
mice.
SUMMARY OF THE INVENTION
[0019] The present invention comprises the provision and use of a
new and improved method and apparatus for quickly and easily
performing ophthalmic electrophysiology on mice.
[0020] In one form of the present invention, there is provided
apparatus for evoking and sensing ophthalmic physiological signals
in an eye, the apparatus comprising:
[0021] an elongated tubular light pipe having a longitudinal axis,
a distal end and a proximal end, the distal end terminating in a
spheroid recess;
[0022] an active electrode having a distal end and a proximal end,
the active electrode being mounted to the elongated tubular light
pipe and extending proximally along the elongated tubular light
pipe so that the distal end of the active electrode terminates at
the spheroid recess at the distal end of the elongated tubular
light pipe; and
[0023] a reference electrode having a distal end and a proximal
end, the reference electrode being mounted to the elongated tubular
light pipe and extending proximally along the elongated tubular
light pipe so that the distal end of the reference electrode
terminates at the spheroid recess at the distal end of the
elongated tubular light pipe;
[0024] wherein the distal end of the active electrode is located
closer to the longitudinal axis of the elongated tubular light pipe
than the distal end of the reference electrode.
[0025] In another form of the present invention, there is provided
a method for evoking and sensing ophthalmic physiological signals
in an eye, the method comprising:
[0026] providing apparatus comprising: [0027] an elongated tubular
light pipe having a longitudinal axis, a distal end and a proximal
end, the distal end terminating in a spheroid recess; [0028] an
active electrode having a distal end and a proximal end, the active
electrode being mounted to the elongated tubular light pipe and
extending proximally along the elongated tubular light pipe so that
the distal end of the active electrode terminates at the spheroid
recess at the distal end of the elongated tubular light pipe; and
[0029] a reference electrode having a distal end and a proximal
end, the reference electrode being mounted to the elongated tubular
light pipe and extending proximally along the elongated tubular
light pipe so that the distal end of the reference electrode
terminates at the spheroid recess at the distal end of the
elongated tubular light pipe; [0030] wherein the distal end of the
active electrode is located closer to the longitudinal axis of the
elongated tubular light pipe than the distal end of the reference
electrode;
[0031] positioning the elongated tubular light pipe against the eye
of a test subject; and
[0032] introducing light into the proximal end of the elongated
tubular light pipe.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] These and other objects and features of the present
invention will be more fully disclosed or rendered obvious by the
following detailed description of the preferred embodiments of the
invention, which is to be considered together with the accompanying
drawings wherein like numbers refer to like parts, and further
wherein:
[0034] FIGS. 1 and 2 are schematic views of a prior art rodent
table for the ColorDome Stimulator of Diagnosys LLC;
[0035] FIG. 3 is a schematic view of a prior art GoldLens Corneal
Electrode;
[0036] FIG. 4 are schematic views showing prior art Burian speculum
type electrodes and prior art cotton wick electrodes;
[0037] FIG. 5 is a schematic view showing a prior art mouse ERG
electrode;
[0038] FIGS. 6-12 are schematic views showing novel apparatus
formed in accordance with the present invention for evoking and
sensing ophthalmic physiological signals in an eye;
[0039] FIG. 13 is a schematic view showing an alternative form of
the apparatus shown in FIGS. 6-12;
[0040] FIG. 14 is a schematic view showing another alternative form
of the apparatus shown in FIGS. 6-12; and
[0041] FIGS. 15-17 are schematic views showing exemplary novel
apparatus formed in accordance with the present invention for
evoking and sensing ophthalmic physiological signals in an eye.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0042] The present invention provides a new and improved approach
for quickly and easily performing ophthalmic electrophysiology on
mice.
[0043] More particularly, and looking now at FIGS. 6-11, there is
shown a combined stimulator and bipolar electrode assembly 5 formed
in accordance with the present invention. Combined stimulator and
bipolar electrode assembly 5 generally comprises a housing 10, a
light pipe subassembly 15 and a light source subassembly 20.
[0044] Housing 10 preferably comprises a main body 22 having a
cavity 25 formed therein, and a side arm 30 extending at an angle
(e.g., 125 degrees) to the longitudinal axis of main body 22. Side
arm 30 includes a cavity 35 formed therein, and a magnetic mount 40
(preferably in the form of a steel ball) secured to side arm
30.
[0045] Light pipe subassembly 15 is disposed partially within, and
protrudes from, cavity 25 of main body 22. Light pipe subassembly
15 generally comprises a light pipe 45 formed out of a
light-transmissive material (e.g., Plexiglass) and having a distal
end 50 and a proximal end 55. Light pipe 45 has an elongated
configuration, and may be cylindrical (e.g., substantially straight
with a substantially circular cross-section), or non-linear
pseudo-cylindrical (e.g., bent or curved with a substantially
circular cross-section), or light pipe 45 may have another
acceptable configuration. Distal end 50 of light pipe 45 has a
spheroid recess 60 formed therein. The radius of curvature of
spheroid recess 60 is preferably similar to the radius of curvature
of the eye of a mouse, so that the distal end 50 of light pipe 45
can be seated against the outside surface of the eye of a mouse.
Light pipe 45 also comprises a pair of slots 65A, 65B formed in the
outer surface of light pipe 45. In one preferred form of the
invention, slots 65A, 65B are diametrically opposed to one another.
The distal end of slot 65A has a greater depth than the remainder
of slot 65A, so that the distal end of slot 65A approaches (but
preferably does not reach) the center of spheroid recess 60.
Preferably at least the distal portion of slot 65A outboard of wire
70A is filled with an appropriate material (e.g., a
light-transmissive, non-conductive, waterproof material) so as to
eliminate air gaps between light pipe 45 and the eye of the mouse.
A platinum (or silver or gold, etc.) wire 70A, which serves as the
active electrode for combined stimulator and bipolar electrode
assembly 5, is disposed in slot 65A. Note that the distal end of
platinum wire 70A follows the floor of slot 65A so that the distal
end of platinum wire 70A approaches the center of spheroid recess
60. The distal end of platinum wire 70A communicates with spheroid
recess 60. A platinum (or silver or gold, etc.) wire 70B, which
serves as the reference electrode for combined stimulator and
bipolar electrode assembly 5, is disposed in slot 65B. The distal
end of platinum wire 70B also communicates with spheroid recess 60.
Preferably at least the distal portion of slot 65B outboard of wire
70B is filled with an appropriate material (e.g., a
light-transmissive, non-conductive, waterproof material) so as to
eliminate air gaps between light pipe 45 and the eye of the mouse.
Note that the distance between the distal end of platinum wire 70A
(which will act as the active electrode) and the distal end of
platinum wire 70B (which will act as the reference electrode) is
substantially equal to the distance between a portion of the eye
which exhibits an evoked physiological signal and a portion of the
eye which exhibits a lesser evoked physiological signal (or,
preferably, does not exhibit an evoked physiological signal), e.g.,
the distance between the cornea and the perimeter of the eye. The
intermediate portions of platinum wires 70A, 70B may be held to the
body of light pipe 45 with shrink bands 75. The proximal end 55 of
light pipe 45 is disposed in cavity 25 of main body 20, and the
proximal ends of platinum wires 70A, 70B are passed through cavity
35 of side arm 30 so that they can be brought out the proximal end
80 of side arm 30 for connection to appropriate amplification
(e.g., by a differential amplifier) and processing electronics (not
shown) for ERG signal processing.
[0046] Light source subassembly 20 is disposed within cavity 25 of
main body 20. Light source subassembly 20 generally comprises LEDs
85 for generating light, and any appropriate optics (not shown)
required to transmit the light generated by LEDs 85 into the
proximal end 55 of light pipe 45, whereupon the light will travel
down the length of light pipe 45 to the distal end 50 of light pipe
45. A power line 90 provides power to LEDs 85. Preferably a wire
mesh 95 (or similar element) is provided distal to LEDs 85 and
proximal to platinum wires 70A, 70B so as to provide
electromagnetic interference (EMI) shielding between LEDs 85 and
platinum wires 70A, 70B.
[0047] It will be appreciated that, on account of the foregoing
construction, combined stimulator and bipolar electrode assembly 5
can be supported via its magnetic mount 40 for use with an ERG
mouse platform, with the proximal ends of platinum wires 70A, 70B
being connected to appropriate amplification and processing
electronics for ERG signal processing, and with power line 90 being
connected to an appropriate source of power. When a mouse is to be
tested, the mouse is placed on the ERG mouse platform, a ground
electrode (not shown) is attached to the mouse, and then housing 10
can be moved so as to bring the distal end 50 of light pipe 45 into
contact with the eye of the mouse. This action will position the
distal end of platinum wire 70A (i.e., the active electrode) at the
appropriate position on the eye of the mouse, and will
simultaneously position the distal end of platinum wire 70B (i.e.,
the reference electrode) at another appropriate position on the eye
of the mouse. When LEDs 85 are thereafter energized, the light from
LEDs 85 passes down light pipe 45 and into the eye of the mouse,
whereby to stimulate the eye of the mouse. Platinum wires 70A
(i.e., the active electrode) and 70B (i.e., the reference
electrode) pick up the electrophysiological response of the eye of
the mouse as electrical signals, and these electrical signals are
passed along platinum wires 70A, 70B to appropriate amplification
and processing electronics for ERG signal processing.
[0048] Thus it will be seen that with the combined stimulator and
bipolar electrode assembly 5 of the present invention, the assembly
simultaneously provides (i) the stimulator needed for conducting
ophthalmic electrophysiology on a mouse (i.e., LEDs 85 and light
pipe 45), (ii) the bipolar electrode needed for conducting
ophthalmic electrophysiology on a mouse (i.e., platinum wires 70A,
70B supported by light pipe 45), and (iii) the support structure
(e.g., magnetic mount 40) for holding the bipolar electrode
securely against the eye during testing.
[0049] Significantly, mounting platinum wires 70A, 70B to the light
pipe 45 provides a robust mechanical support for the platinum
wires, making it possible to quickly, easily and precisely position
the active electrode (i.e., platinum wire 70A) and the reference
electrode (i.e., platinum wire 70B) on the eye of the mouse. At the
same time, the small acceptance angle of light pipe 45 restricts
the light reaching the eye of the mouse to that generated by LEDs
85, which eliminates the normal need for a large Ganzfeld to
conduct ophthalmic electrophysiology. Note that LEDs 85 may be a
three-color RGB system, although UV could also be used and would be
desirable in mice. In one preferred form of the invention,
appropriate electronic drivers are provided to drive RGB LEDs 85
accurately enough to form precisely-defined metameric colors.
[0050] If desired, and looking now at FIG. 12, light pipe 45 may
comprise a main body 45A and an end diffuser 45B. End diffuser 45B
can, advantageously, help provide full retinal illumination. More
particularly, end diffuser 45B acts to broaden the angle at which
light exits main body 45A of light pipe 45 and enters the eye of
the mouse, and ensures that light exiting the light pipe is
distributed equally to all parts of the retina of the mouse. The
diffusing material of end diffuser 45B is preferably of non-uniform
thickness, i.e., it is made thinner at the edges to compensate for
the lower flux density occurring at the perimeter of the light
pipe. Furthermore, if desired, reference electrode 70B may be
"doubled over" so as to increase the surface area contact of
reference electrode 70B with the eye of the mouse. And, if desired,
and looking now at FIG. 13, a conductive foil (or conductive film)
100 may be provided at distal end 50 of light pipe 45, with
conductive foil (or conductive film) 100 electrically connected to
reference electrode 70B so as to increase the surface area contact
of reference electrode 70B with the eye of the mouse.
[0051] In some cases, it can be helpful to provide the user with
"red light" illumination to help the user set the combined
stimulator and bipolar electrode assembly 5 against the eye of the
mouse. To this end, if desired, and looking now at FIG. 14, a
light-transmissive sleeve 105 may be disposed coaxially about light
pipe 45, with light-transmissive sleeve 105 acting as an additional
light pipe for delivering red light to the distal end of light pipe
45. More particularly, in this form of the invention, when red
light is introduced into the proximal end of light-transmissive
sleeve 105, a ring of red light will be provided at the distal end
of light-transmissive sleeve 105, whereby to provide a rim of red
illuminating light about the distal perimeter of light pipe 45.
[0052] The combined stimulator and bipolar electrode assembly 5 of
the present invention can be set up not only more accurately, but
also much more quickly, than the present state-of-the-art, even by
relatively unskilled personnel. After positioning the mouse on the
heated table described above and inserting the ground electrode
(e.g., in the haunch or tail of the animal), the combined
stimulator and bipolar electrode assembly 5 is simply brought into
contact with the eye of the mouse by moving housing 10 (which
causes magnetic mount 40, e.g., a steel ball, to roll within a
magnetic cup, e.g., a magnetic ball holder (see FIG. 1 above, which
shows a magnetic ball holder of the sort which may be used), and
then the test is ready to run. A second device can be used
simultaneously on the fellow eye (i.e., the other eye of the mouse)
if desired. This eliminates several minutes fumbling in near
darkness to carefully adjust the electrodes and position the
Ganzfeld. Additionally, since light pipe subassembly 15 is held in
position against the eye by an external mechanical mount (i.e.,
magnetic mount 40) and is not supported by the eye per se, it is
not necessary to use particular care to position combined
stimulator and bipolar electrode assembly 5 precisely against
structurally robust eye tissue. Furthermore, since light pipe
subassembly 15 has no accessible distal surface once it is seated
against the eye, it is substantially impossible to obscure the
light path from light pipe subassembly 15 into the eye by the use
of excessive saline.
[0053] Testing of the combined stimulator and bipolar electrode
assembly 5 on mice has yielded excellent results. It produces
expected waveforms with very little noise, although the overall
amplitude of the waveforms is small.
[0054] In addition to the foregoing, some investigators have used
an active electrode in one eye, and a reference electrode in the
other eye. This technique still involves accurate placement of two
corneal wires (extremely challenging with prior art electrodes),
but the fellow eye makes an excellent impedance-matched reference.
However, with this approach, care must be taken to avoid light
crosstalk between the eyes--the reference eye must not receive any
stimulus light.
[0055] Using the combined stimulator and bipolar electrode assembly
5 of the present invention solves both problems (i.e., accurate
placement of electrode and avoiding light crosstalk between the
eyes). More particularly, in one form of the invention, the corneal
electrode 70A of, for example, the right eye is plugged into the
active side of the differential amplifier, and the corneal
electrode 70A of the left eye into the reference side of the
differential amplifier. The electrodes in each eye are
automatically correctly positioned. The eyes are then stimulated
one at a time using the light source subassemblies 20 of the
combined stimulator and bipolar electrode assemblies 5, and there
is no optical crosstalk because of the light pipe configuration
(i.e., the positioning of a light pipe on an eye of the mouse
limits the light reaching that eye of the mouse to only the light
transmitted by that light pipe). When the right eye is being
driven, the signal is normally polarized, and when the left eye is
being driven, the signal is inverted. Alternatively, both eyes of
the mouse could be simultaneously stimulated using light source
subassemblies 20 of the combined stimulator and bipolar electrode
assemblies 5, and the differential between the two corneal
electrodes 70A may be measured so as to identify differences in eye
function.
[0056] Alternatively, the reference electrodes 70B may be used in
place of the corneal electrodes 70A. In this form of the invention,
the reference electrode 70B of, for example, the right eye is
plugged into the active side of the differential amplifier, and the
reference electrode 70B of the left eye is plugged into the
reference side of the differential amplifier. The electrodes in
each eye are automatically correctly positioned. The eyes are then
stimulated one at a time using the light source subassemblies 20 of
the combined stimulator and bipolar electrode assemblies 5, and
there is no optical crosstalk because of the light pipe
configuration (i.e., the positioning of a light pipe on an eye of
the mouse limits the light reaching that eye of the mouse to only
the light transmitted by that light pipe). When the right eye is
being driven, the signal is correctly polarized, and when the left
eye is being driven, the signal is inverted. Alternatively, both
eyes of the mouse may be simultaneously stimulated using light
source subassemblies 20 of the combined stimulator and bipolar
electrode assemblies 5, and the differential between the two
reference electrodes 70B may be measured so as to identify
differences in eye function.
[0057] In one preferred form of the invention, and looking now at
FIGS. 15-17, platinum wire 70A can be omitted and platinum wire 70B
can be provided with a conductive foil (or conductive film) 100.
When configured in this manner, the present invention essentially
comprises a combined stimulator and monopolar electrode assembly.
This form of the invention can be advantageous where combined
stimulator and monopolar electrode assemblies are positioned
against both eyes of the mouse (for stimulating one eye at a time
or for simultaneously stimulating both eyes at the same time).
[0058] The robustness of the electrical and optical connections
that the new combined stimulator and bipolar electrode assembly 5
makes with the mouse has been dramatically demonstrated during
testing. Toward the end of testing, the mice may wake up and begin
to move. With conventional setups, the first movement of the
awakening mouse breaks corneal contact and the testing is over.
With the combined stimulator and bipolar electrode assembly 5 of
the present invention, contact with the awakening mouse was
successfully maintained even though the mouse was moving and
testing continued with good results until the mouse literally
walked away.
[0059] In the foregoing disclosure, platinum wire 70A (i.e., the
active electrode) is disposed within slot 65A which extends along
an outer surface of light pipe 45, and platinum wire 70B (i.e., the
reference electrode) is disposed within slot 65B which extends
along an outer surface of light pipe 45. However, if desired, slot
65A could be replaced with a bore extending longitudinally through
light pipe 45 and platinum wire 70A (i.e., the active electrode)
may be disposed within this longitudinal bore, and/or slot 65B
could be replaced with another bore extending longitudinally
through light pipe 45 and platinum wire 70B (i.e., the reference
electrode) may be disposed within this other longitudinal bore. In
such a construction, the longitudinal bore receiving platinum wire
70A (i.e., the active electrode) is disposed closer to the
longitudinal axis of light pipe 45 than the longitudinal bore
receiving platinum wire 70B (i.e., the reference electrode).
Modifications of the Preferred Embodiments
[0060] It should be understood that many additional changes in the
details, materials, steps and arrangements of parts, which have
been herein described and illustrated in order to explain the
nature of the present invention, may be made by those skilled in
the art while still remaining within the principles and scope of
the invention.
* * * * *