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Device allows needle-free injections
into smallest vessels
By
Dan Keller
WASHINGTON,
DC - A new low- cost and needle-free liquid microjet device could
prove useful for the delivery of thrombolytic drugs to treat small-vessel
occlusions in the eye, according to a report at a Research to Prevent
Blindness Foundation seminar.
The device, called a pulsed liquid microjet, delivers picolitre
to microlitre volumes. A high voltage wire electrode and surrounding
grounded metal sheath sit inside a tapered capillary tube micronozzle.
When short duration voltages are applied, current flows from the
central electrode to the sheath and heat causes the explosive growth
of a vapour bubble, ejecting liquid. The velocity, volume, penetration
depth and diameter of the expelled jet depend on the energy of the
electric discharge and the diameter of the exit hole in the nozzle.
In experiment studies, the device produced a jet that penetrated
a vessel 60 micrometers in diameter but left the opposite vessel
wall intact. This could prove useful for localised injection in
ocular vessels, Daniel Palanker PhD said.
Using 0.7% agarose gel as a test medium, Dr Palanker documented
penetration depths with varying discharge energies. The micronozzle
was loaded with microscopic polystyrene beads suspended in isotonic
saline and positioned in contact with the agarose surface immersed
in saline.
A discharge energy of 0.16 mJ caused penetration to a depth of 80
micrometers while a 1.56 mJ discharge ejected a jet to a depth of
500 micrometers.
In vitro experiments on excised chorioallantoic membrane of a chicken
embryo showed that the microjet could penetrate the proximal wall
of a 60 micrometer diameter vessel and inject fluorescent dye.
Fluorescence microscopy showed that with repeated pulses from the
microjet the dye was confined to the vessel and moved in the direction
of blood flow.
Dr Palanker noted that to be clinically useful, a surgeon must be
able to hold and position the probe against a pulsating vessel.
Experiments in vivo on chicken chorioallantoic membrane demonstrated
that an operator could inject a 100 micrometer diameter artery under
physiological conditions with a handheld probe.
Microscopic examination of histological sections of the artery showed
tissue damage was confined to a zone approximately 20 micrometers
in diameter and only the proximal wall was penetrated. Bleeding
lasted only a few seconds. The endothelium of the distal wall was
not damaged.
"This device will permit procedures currently impossible to
perform including the direct injection of pharmaceuticals into very
small vessels such as the retinal arterioles and venules in an atraumatic
fashion compared with direct cannulation," Mark Blumenkranz
MD remarked.
The pulsed liquid microjet may allow intradermal or transdermal
injections as well as injections into the brain, heart or other
organs. It may also permit injection of recombinant material or
cells into organs or cells themselves with less pain and trauma
than conventional needles and cannulas.
The device may enter clinical practice in two or three years depending
on the pace of clinical trials, Dr Blumenkranz predicted.
Pulsed electrical discharges also form the basis of a new device
that can provide tractionless cutting of tissues ranging from soft
membranes to bone, with independent control over the width and depth
of the cut.
Dr Palanker foresees early applications in vitreoretinal surgery
and capsulotomy. Currently, traction accompanying mechanical segmentation,
peeling or delamination of vitreoretinal membranes can damage retina
and cause tears and bleeding.
Various types of lasers for such applications have had their own
problems, including collateral damage of surrounding tissues, harmful
effects of radiation, high costs and large size, he noted.
The microjet device generates pulsed waveforms that cause the formation
of a thin layer of pulsed plasma around an elongated microelectrode
in a conductive fluid.
The elongated shape results in dissection with the edges of the
electrode not only with its apex and therefore no connections remain
between the two edges of the cut surface.
Animal tests have shown the device efficiently dissects retina,
lens capsule, sclera and iris. It may be applicable to vitreoretinal,
cataract and glaucoma surgery.
Dr Palanker showed a video of smooth dissection of a chicken embryo
membrane. Microscopic examination showed the cuts had very clean
edges.
"It will be possible to do sclerotomies without sutures due
to the small diameter of the instrument which can be up to 0.25
mm (30 Gauge needle). We basically remove the instrument and tissue
seals by itself.
"It also allows a blind capsulotomy where you can cut under
the iris without actually seeing the edge," he said
He added that the new tool will also be useful in cases of mature
cataract where the surgeon cannot see the capsule. The microjet
device is described by Dr Palanker and colleagues in an article
in the September 2002 issue of the Archives of Ophthalmology.
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