U.S. patent application number 10/178271 was filed with the patent office on 2002-10-31 for method for depositing a flattened droplet on a surface and apparatus therefor, and a pump therefor.
This patent application is currently assigned to A.R.T. Medical Instruments Ltd.. Invention is credited to Berger, Abraham, Haim, Ben Zion, Hazan, Avri, Meirovich, Baruch.
Application Number | 20020159921 10/178271 |
Document ID | / |
Family ID | 11070748 |
Filed Date | 2002-10-31 |
United States Patent
Application |
20020159921 |
Kind Code |
A1 |
Berger, Abraham ; et
al. |
October 31, 2002 |
Method for depositing a flattened droplet on a surface and
apparatus therefor, and a pump therefor
Abstract
A method and apparatus therefor for depositing a flattened
droplet on a partially absorbent surface comprising the steps of
providing a narrow bore transfer tube having a proximal end and a
distal end and containing a microvolume of liquid, the proximal end
connected to a pneumatic system adapted for issuing an outgoing
flow of displacement gas into the tube and drawing an incoming flow
of displacement gas therefrom; and issuing an outgoing flow of
displacement gas for slowly discharging substantially the entire
microvolume of liquid as a droplet on the surface and controllably
blowing one or more bubbles into the droplet towards the end of its
discharge for flattening the droplet on the surface. A pump (31)
comprising a housing (33) having a bore (34) with an internal
peripheral surface (36), and a stationary annular sealing member
(48) integrally formed therewith at a first end (37) of a pair of
opposite ends (37 and 38); a slide rod (39) disposed in the bore
and having an external peripheral surface (41) and a displaceable
annular sealing member (49) integrally formed therewith; the
sealing members sealing the peripheral surfaces to define a vented
displacement volume (51) therebetween whose volume is proportional
to an annular cross section area between the peripheral surfaces
and a distance between the sealing members; and the slide rod being
slidably reciprocable between first and second positions
respectively toward and away from the stationary sealing member
whereupon the displaceable sealing member moves to reduce the
volume to issue an outgoing flow of displacement gas from the
displacement volume on a downstroke of the slide rod from its
second position to its first position and the displaceable sealing
member moves to increase the volume to draw an incoming flow of
displacement gas into the displacement volume on an upstroke of the
slide rod from its first position to its position.
Inventors: |
Berger, Abraham; (Givataim,
IL) ; Haim, Ben Zion; (Holon, IL) ; Meirovich,
Baruch; (Hod Hasharon, IL) ; Hazan, Avri;
(Givataim, IL) |
Correspondence
Address: |
Gary M. Nath
NATH & ASSOCIATES PLLC
6th Floor
1030 15th Street, N.W.
Washington
DC
20005
US
|
Assignee: |
A.R.T. Medical Instruments
Ltd.
Hasharon
IL
|
Family ID: |
11070748 |
Appl. No.: |
10/178271 |
Filed: |
June 25, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10178271 |
Jun 25, 2002 |
|
|
|
09529065 |
Jul 5, 2000 |
|
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6420186 |
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Current U.S.
Class: |
422/400 ; 222/3;
222/372; 222/385; 422/67; 435/286.4; 436/180; 436/54; 436/63;
436/65; 73/863.71; 73/864; 73/864.01; 73/864.11; 73/864.15;
73/864.34 |
Current CPC
Class: |
Y10T 436/119163
20150115; A61B 17/435 20130101; Y10T 436/2575 20150115; A61D 19/04
20130101 |
Class at
Publication: |
422/100 ;
436/180; 436/54; 436/63; 436/65; 222/3; 222/372; 222/385; 422/67;
435/286.4; 73/863.71; 73/864; 73/864.01; 73/864.11; 73/864.15;
73/864.34 |
International
Class: |
G01N 001/10; G01N
035/08 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 14, 1997 |
IL |
121968 |
Oct 14, 1998 |
IL |
PCT/IL98/00498 |
Claims
1. A method for depositing a flattened droplet on a partially
absorbent surface comprising the steps of: (a) providing a narrow
bore transfer tube having a proximal end and a distal end and
containing a microvolume of liquid, the proximal end connected to a
pneumatic system adapted for issuing an outgoing flow of
displacement gas into the tube and drawing an incoming flow of
displacement gas therefrom; and (b) issuing an outgoing flow of
displacement gas for slowly discharging substantially the entire
microvolume of liquid as a droplet on the surface and controllably
blowing one or more bubbles into the droplet towards the end of its
discharge for flattening the droplet on the surface.
2. The method of claim 1 wherein step (a) includes: (a1) preventing
capillary forces to draw liquid into the transfer tube upon the
insertion of its distal end into a vessel containing liquid; (a2)
inserting the transfer tube's distal end into the vessel; (a3)
drawing an incoming flow of displacement gas from the transfer tube
such that a microvolume of liquid is drawn thereinto; and (a4)
removing the transfer tube's distal end from the liquid.
3. The method of claim 2 wherein step (a1) includes issuing an
outgoing flow of displacement gas into the transfer tube.
4. The method of claim 3 further comprising the step of: (a5)
drawing the microvolume of liquid into the transfer tube away from
its distal end; and (a6) neutralizing the inward displacement by a
brief outgoing flow of displacement gas into the transfer tube.
5. The method according to any one of claims 1-4 further comprising
the step of: (c) providing additional outflow of displacement gas
while displacing the transfer tube away from the droplet so
separate the droplet from its distal end.
6. The method according to any one of claims 1-5 wherein the
microvolume of liquid is a culture medium containing embryo(s)
which are urged against the surface by the droplet's prevailing
surface tension.
7. Apparatus for depositing a flattened droplet on a partially
absorbent surface, the apparatus for use with a narrow bore
transfer tube having a proximal end and a distal end and a vessel
of liquid, the apparatus comprising: (a) a pneumatic system
connected to the transfer tube's proximal end and adapted for
issuing an outgoing flow of displacement gas into said transfer
tube and drawing an incoming flow of displacement gas thereinto
from said transfer tube; and (b) a control mechanism for
controlling said pneumatic system in different operational modes
including: an user controlled suction mode for drawing an incoming
flow of displacement gas from said transfer tube whereby a
microvolume of liquid is drawn thereinto prior to the removal of
said distal end from the vessel; and an user initiated automated
delivery mode for issuing an outgoing flow of displacement gas into
said transfer tube for slowly discharging substantially the entire
microvolume of liquid as a droplet on the surface and controllably
blowing one or more bubbles into the droplet towards the end of its
discharge for flattening the droplet on the surface.
8. Apparatus according to claim 7 wherein said control mechanism
includes an automatic pre-suction mode for issuing an outgoing flow
of displacement gas.
9. Apparatus according to claim 7 or 8 wherein separate units house
a suction control unit for controlling said user controlled suction
mode and a transfer control unit for controlling said user
initiated automatic delivery mode.
10. A pump comprising a housing having a bore with an internal
peripheral surface, and a stationary annular sealing member
integrally formed therewith at a first end of a pair of opposite
ends; a slide rod disposed in said bore and having an external
peripheral surface and a displaceable annular sealing member
integrally formed therewith; said sealing members sealing said
peripheral surfaces to define a vented displacement volume
therebetween whose volume is proportional to an annular cross
section area between said peripheral surfaces and a distance
between said sealing members; and said slide rod being slidably
reciprocable between first and second positions respectively toward
and away from said stationary sealing member whereupon said
displaceable sealing member moves to reduce said volume to issue an
outgoing flow of displacement gas from said displacement volume on
a downstroke of said slide rod from said second position to said
first position and said displaceable sealing member moves to
increase said volume to draw an incoming flow of displacement gas
into said displacement volume on an upstroke of said slide rod from
said first position to said second position.
11. The pump according to claim 10 wherein both said bore and said
slide rod are of right cylindrical shape and said cross section
area is defined by .pi.(a.sup.2-b.sup.2) where a and b are the
radii of said internal peripheral surface and said external
peripheral surface, respectively.
12. The pump according to either claim 10 or 11 wherein said cross
section area has an area of about 4-10 mm.sup.2.
13. The pump according to any one of claims 10-12 wherein said
displacement volume can be incrementally changed in the order of
0.1-0.4 .mu.l.
Description
FIELD OF THE INVENTION
[0001] The invention relates to a method for depositing a flattened
droplet on a surface suitable for in vitro fertilization (IVF) and
embryo transfer (ET), and apparatus therefor, and a pump
therefor.
BACKGROUND OF THE INVENTION
[0002] In an IVF-ET procedure, oocytes are aspirated from female
ovaries and inseminated in vitro with male sperm in a culture
medium to form embryos which are incubated prior to their being
transferred to a subject by means of a two-stage transfer
procedure. The transfer procedure includes the aspiration of a
relatively large volume of about 20-40 .mu.l of culture medium
containing between one to five embryos into a transfer catheter by
means of a manually operated syringe and its subsequent injection
into a subject.
[0003] Since a conventional IVF-ET procedure is manual, the rate of
injection of the embryo containing culture into a uterine cavity
may vary significantly. Thus, on the one hand, too slow an
injection rate may cause embryo containing culture medium to
trickle down the transfer catheter's outer surface and, on the
other hand, too quick an injection rate may severely damage
embryo(s) following their collision against a uterine wall. The
latter case may also flood a subject's uterus possibly resulting in
a failed procedure as embryos are either washed out of her uterus
or implanted in one of her Fallopian tubes leading to an ectopic
pregnancy. Another disadvantage attendant with the use of a
relatively large volume of culture medium is that it may alter the
specific properties of the micro-environment within a subject's
uterus required for successful embryo implantation and its normal
development.
[0004] The present invention is based on the notion that
substantially automating embryo implantation in IVF-ET procedures
may overcome some of the shortcomings of the conventional IVF-ET
procedure.
SUMMARY OF THE INVENTION
[0005] In accordance with the present invention, there is provided
a method for depositing a flattened droplet on a surface
particularly suitable for depositing embryo(s) containing culture
medium at a desired site in a uterus cavity, and apparatus
therefor, and a pump therefor.
[0006] In accordance with a first aspect of the invention, there is
provided a method for depositing a flattened droplet on a partially
absorbent surface, the method comprising the steps of:
[0007] (a) providing a narrow bore transfer tube having a proximal
end and a distal end and containing a microvolume of liquid, the
proximal end connected to a pneumatic system for issuing an
outgoing flow of displacement gas into the transfer tube and
drawing an incoming flow of displacement gas thereinto from the
transfer tube; and
[0008] (b) issuing an outgoing flow of displacement gas for slowly
discharging substantially the entire microvolume of liquid as a
droplet on the surface and controllably blowing one or more bubbles
into the droplet towards the end of its discharge to flatten the
droplet on the surface.
[0009] A "flattened droplet" in the context of the present
invention can be demonstrated on standard 80 gram/m.sup.2 A4 paper
for use with ink jet printers, such paper constituting a partially
absorbent surface on which a flattened droplet of the present
invention has a projected surface area about three to six times
larger than that of a naturally forming dome-like droplet. A
"partially absorbent surface" in the context of the present
invention is one which absorbs a relatively insignificant volume of
a naturally forming dome-like droplet over about 60 seconds. The
flattening of a droplet as achieved by the method of the present
invention is not by the relatively slow process of its being
absorbed assuming it does not dry but rather as a consequence of
its being effectively inflated by one or more bubbles of
displacement gas controllably blown thereinto towards the end of
its discharge which typically occurs over 5-20 seconds from an
initial outward displacement of the microvolume of liquid. The
surface may be flat, inclined or even inverted and still maintain
the droplet in its flattened shape by virtue of the prevailing
surface tension therewith.
[0010] A "microvolume of liquid" in the context of the present
invention is a volume of liquid in the microliter range, e.g.,
within the range of 0.05-5 .mu.l, preferably within the range of
0.1-3.0 .mu.l, and particularly within the range of 0.3-2.0 .mu.l.
In the case of an IVF-ET procedure on a human subject when the
catheter is upwardly inclined, even though the discharge of culture
medium is relatively slow, its volume is so small so as to avoid a
downward trickle along the catheter's outer surface.
[0011] In accordance with a preferred embodiment of the present
invention, step (a) includes:
[0012] (a1) preventing capillary forces to draw liquid into the
transfer tube upon insertion of its distal end into a vessel
containing liquid;
[0013] (a2) inserting the transfer tube's distal end into the
liquid;
[0014] (a3) drawing an incoming flow of displacement gas from the
transfer tube such that a microvolume of liquid is drawn thereinto;
and
[0015] (a4) removing the transfer tube's distal end from the
liquid.
[0016] The step of preventing capillary forces is preferably
achieved by issuing an outgoing flow of displacement gas into the
transfer tube so as to create a positive pressure therein.
Alternatively, this step can be achieved, for example, by providing
a seal at its distal end. After the transfer tube's distal end is
removed from the liquid, the microvolume of liquid is preferably
inwardly drawn away from its distal end as a safety precaution
whereafter the inward displacement is neutralized by a brief
outgoing flow of displacement gas into the transfer tube.
[0017] After the discharge of the microvolume of liquid from the
transfer tube, the flattened droplet in most cases is still
connected to the transfer tube's distal end and therefore to
prevent its suction back into the transfer tube, the outgoing flow
of displacement gas is maintained until the droplet is disconnected
from the transfer tube's distal end by manually withdrawing the
transfer tube. This outgoing flow of displacement gas may also
remove any small quantities of the microvolume which were not
initially discharged and which may include an embryo(s) in an
IVF-ET procedure.
[0018] In accordance with a second aspect of the present invention,
there is provided apparatus for depositing a flattened droplet of
liquid on a partially absorbent surface, the apparatus for use with
a narrow bore transfer tube having a proximal end and a distal end
and a vessel of liquid, the apparatus comprising:
[0019] (a) a pneumatic system connected to the transfer tube's
proximal end and adapted for issuing an outgoing flow of
displacement gas into said transfer tube and drawing an incoming
flow of displacement gas thereinto from said transfer tube; and
[0020] (b) a control mechanism for controlling said pneumatic
system in different operational modes including:
[0021] a user controlled suction mode for drawing an incoming flow
of displacement gas from the transfer tube whereby a microvolume of
liquid is drawn thereinto prior to the removal of said distal end
from the vessel; and
[0022] a user initiated automated delivery mode for issuing an
outgoing flow of displacement gas into the transfer tube for slowly
discharging substantially the entire microvolume of liquid as a
droplet on the surface and controllably blowing one or more bubbles
into the droplet towards the end of its discharge to flatten the
droplet on the surface.
[0023] In accordance with a third aspect of the present invention,
there is provided a pump comprising a housing having a bore with an
internal peripheral surface, and a stationary annular sealing
member integrally formed therewith at a first end of a pair of
opposite ends; a slide rod disposed in said bore and having an
external peripheral surface and a displaceable annular sealing
member integrally formed therewith; said sealing members sealing
said peripheral surfaces to define a vented displacement volume
therebetween whose volume is proportional to an annular cross
section area between said peripheral surfaces and a distance
between said sealing members; and said slide rod being slidably
reciprocable between first and second positions respectively toward
and away from said stationary sealing member whereupon said
displaceable sealing member moves to reduce said volume to issue an
outgoing flow of displacement gas from said displacement volume on
a downstroke of said slide rod from said second position to said
first position and said displaceable sealing member moves to
increase said volume to draw an incoming flow of displacement gas
into said displacement volume on an upstroke of said slide rod from
said first position to said second position.
[0024] Preferably both the bore and the slide rod are of a right
cylindrical shape such that the displacement volume has a cross
sectional area defined by .pi.(a.sup.2-b.sup.2) where a and b are
the radii of the bore's internal peripheral surface and the slide
rod's external peripheral surface, respectively. Preferably, the
cross section area is in the order of 4-10 mm.sup.2 and the pump
has a displacement volume incrementally changeable in the order of
0.1-0.4 .mu.l.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] In order to understand the invention and how it is used, a
preferred embodiment will now be described by way of a non-limiting
example only, with reference to the accompanying drawings in
which:
[0026] FIG. 1 is a pictorial view of apparatus for depositing a
flattened droplet on a surface in accordance with the present
invention;
[0027] FIGS. 2A-2L illustrates operation of the apparatus of FIG. 1
for depositing the flattened droplet on the surface;
[0028] FIG. 3 is a pictorial view of a pump in accordance with the
present invention; and
[0029] FIGS. 4 and 5 are cross sectional views of the pump of FIG.
3 along lines A-A and B-B in FIG. 3, respectively.
DETAILED DESCRIPTION OF THE DRAWINGS
[0030] With reference now to FIGS. 1 and 2, apparatus 1 is employed
for depositing a flattened droplet F on a partially absorbent
surface S, for example, on a subject's endometrium in an IVF-ET
procedure. Apparatus 1 includes a suction control unit 2 normally
permanent located in a laboratory for the preparation of an embryo
carrying catheter 3 constituting a transfer tube, a transfer
control unit 4 normally permanently located in a treatment room
where an IVF-ET procedure is carried out and a portable casing 6
for consecutive connection to the suction control unit 2 and the
transfer control unit 4 by means of connectors 7 and 8. The casing
6 includes a pneumatic system 9 which is permanently connected to
the catheter 3 during an entire IVF-ET procedure via suitable air
tubing 11 and an air filter 12. The casing 6 also has a receptacle
13 for accommodating the catheter 3 during its transport from the
laboratory to the treatment room.
[0031] The pneumatic system 9 is under a control mechanism 14
including a computer mouse 16 for controlling the suction control
unit 2 for initiating a user controlled suction mode to prepare the
catheter 3 with a microvolume of embryo containing culture medium
and a foot pedal 17 for controlling the transfer control unit 4 for
initiating a user initiated automated delivery mode for depositing
the flattened droplet F on the surface S. The computer mouse 16 has
an upstroke control 18 for drawing an incoming flow of displacement
gas into the pneumatic system 9 from the catheter 3, a downstroke
control 19 for issuing an outgoing flow of displacement gas from
the pneumatic system 9 into the catheter 3 and optionally a speed
control 21 for controlling the flow rate of the displacement gas
either from or into the pneumatic system 9. The suction control
unit 2 is also provided with a reset button 22 for priming the
pneumatic system 9 for a pre-suction mode of issuing an outgoing
flow of displacement gas as indicated by a READY indicator light 23
prior to the preparation of the catheter 3. The different stages of
the automatic delivery mode are indicated by a READY indicator
light 24, a GO indicator light 26 and a DONE indicator light
27.
[0032] In operation, the casing 6 is initially connected to the
suction control unit 2 and the catheter 3 is connected to the
pneumatic system 9 via the air tubing 11 and the filter 12. An
operator presses the reset button 22 whereupon a lit READY
indicator light 23 indicates an outgoing flow of displacement gas
creating a positive pressure within catheter 3 to prevent capillary
forces drawing culture medium thereinto upon insertion of its
distal end 3A into a vessel of culture medium C containing embryos
E shown exaggerated in all FIGS. 2A-2L (see FIG. 2A). The operator
inserts the distal end 3A into the vessel of culture medium C for
aspirating about 0.3 to 0.6 .mu.l microvolume of culture medium
containing an embryo E into the catheter 3 (see FIG. 2B). Once an
embryo is clearly seen to be close to the catheter's distal end 3A,
the rate of aspiration of culture medium may be increased by
depressing the speed control 21. If a single embryo is to be
transferred, distal end 3A is then be removed from the culture
medium otherwise additional embryos may be captured as shown.
[0033] Once the catheter 3 contains one or more embryos, the
operator withdraws its distal end 3A from the culture medium and
then proceeds to depress the downstroke control 19 to slowly
displace the microvolume of culture medium inwardly (see FIG. 2C).
After the microvolume of culture medium has been inwardly displaced
by about 5-15 mm from the catheter's distal end 3A, its motion is
arrested by a momentary outgoing flow of displacement gas (see FIG.
2D) so that it finally comes to rest at a distance of about 10 mm
(see FIG. 2E) therefrom thereby ensuring that it cannot be
inadvertently lost during transportation of the casing 6 between
the laboratory and the treatment room. The catheter 3 is then
placed in the receptacle 13 (see FIG. 1) during the transportation
of the casing 6 from the laboratory to the treatment room.
[0034] For transfer of the embryos E onto the surface S, the
catheter 3 is laid on the surface S (see FIG. 2F) whereupon a first
depression on the foot pedal 17 causes the READY indicator light 24
to be lit indicating that the automatic delivery mode can be
initiated. Thereafter, a second depression on the foot pedal 17
causes the GO indicator light 26 to be lit indicating that an
outgoing flow of displacement gas is displacing the microvolume of
culture medium towards the catheter's distal end 3A (see FIG. 2G).
The outgoing flow of displacement gas causes a concave shaped
meniscus to be slowly formed which increases in size until it
suddenly ruptures whereby most of the microvolume of culture medium
is discharged as a droplet D on the surface S (see FIGS. 2H and
2J). The discharge is accompanied by one or more air bubbles B for
effectively inflating the droplet D thereby considerably widening
its projected surface area on the surface S to form the flattened
droplet F whose shape is maintained by its prevailing surface
tension with the surface S (see FIG. 2K).
[0035] The GO indicator light 26 is then extinguished indicating
that the operator should slightly withdraw the catheter 3 so as to
detach it from the droplet F whilst at the same time there is an
outgoing flow of displacement gas (see FIG. 2L). In the case of an
actual IVF-ET procedure, withdrawal is limited to between about
10-15 mm such that the catheter's distal end 3A still lies along a
subject's endometrium. Finally, a further outgoing flow of
additional displacement gas is provided so as to remove any culture
medium which may remain in the catheter 3. The DONE indicator light
27 is then lit to indicate that the catheter 3 can be completely
removed.
[0036] With reference now to FIGS. 3-5, a pump 31 constituting a
pneumatic system for use with the apparatus 1 includes a base 32
with a housing 33 having a longitudinal right cylindrical
throughbore 34 with an internal peripheral surface 36 of a radius a
and having first and second opposite ends 37 and 38. A right
cylindrical slide rod 39 with an external peripheral surface 41 of
a radius b and first and second opposite end 42 and 43 is disposed
in the bore 34 and is slidingly reciprocated by means of a linear
actuator screw 44 driven by a step motor 46.
[0037] A sleeve bearing 47 having a sealing O-ring gasket 48
constituting a stationary annular sealing member is disposed at the
first end 37 and an O-ring gasket 49 constituting a displaceable
annular sealing member is disposed at the slide rod end 42, the
gaskets 48 and 49 sealingly the peripheral surfaces 36 and 41 to
define a displacement volume 51 vented by a vent 52. The
displacement volume 51 has a volume equal to a product of a cross
sectional area between the surface 36 and 41 defined by
.pi.(a.sup.2-b.sup.2) and the distance between the gaskets 48 and
49.
[0038] The slide rod 39 is slidingly reciprocable between first and
second positions respectively toward and away from the gasket 48
whereupon the displacement volume 51 has a minimum value when the
gaskets 48 and 49 are adjacent in which case a major portion of the
slide rod 39 is exterior to the bore 34 and a maximum value when
the gaskets 48 and 49 are remote from one another. In operation,
the gasket 49 moves to reduce the volume of the displacement volume
51 to issue an outgoing flow of displacement gas therefrom on a
downstroke of the slide rod 39 from its second position to its
first position and the gasket 49 moves to increase the volume of
the displacement volume 51 to draw an incoming flow of displacement
gas thereinto on an upstroke of the slide rod 39 from its first
position to its second position.
[0039] The bore 34 and the slide rod 39 typically have diameters in
the range of about 5-10 mm and which differ in the range of about
0.3-0.7 mm such that the cross section area is in the order of
about 4-10 mm.sup.2. The threading on actuator screw 44 is designed
such that each step of the motor 45 causes an incremental movement
of the slide rod 39 of about 0.001-0.002 inches. The motor 45 is
typically driven at a rate of about 20-300 steps per second.
[0040] Various modifications and changes may be made in the
configuration described above that come within the spirit of the
invention. The invention embraces all such changes and
modifications coming within the scope of the appended claims.
* * * * *