U.S. patent application number 12/721030 was filed with the patent office on 2010-07-08 for handheld transdermal drug delivery and analyte extraction.
This patent application is currently assigned to TRANSPHARMA MEDICAL LTD.. Invention is credited to Ze'ev Sohn.
Application Number | 20100174224 12/721030 |
Document ID | / |
Family ID | 29251162 |
Filed Date | 2010-07-08 |
United States Patent
Application |
20100174224 |
Kind Code |
A1 |
Sohn; Ze'ev |
July 8, 2010 |
HANDHELD TRANSDERMAL DRUG DELIVERY AND ANALYTE EXTRACTION
Abstract
Apparatus is provided for facilitating delivery of a substance
through skin of a subject. The apparatus includes a handle and a
cartridge, removably coupled to the handle. The cartridge includes
one or more electrodes and a patch comprising the substance, the
electrodes adapted to be applied to a region of the skin, and the
patch adapted to be applied to at least a portion of the region of
the skin by removal of the electrodes therefrom.
Inventors: |
Sohn; Ze'ev; (Ginot Shomron,
IL) |
Correspondence
Address: |
DARBY & DARBY P.C.
P.O. BOX 770, Church Street Station
New York
NY
10008-0770
US
|
Assignee: |
TRANSPHARMA MEDICAL LTD.
Yehud
IL
|
Family ID: |
29251162 |
Appl. No.: |
12/721030 |
Filed: |
March 10, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10511966 |
Dec 30, 2004 |
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PCT/IL03/00314 |
Apr 15, 2003 |
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12721030 |
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60374224 |
Apr 19, 2002 |
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Current U.S.
Class: |
604/20 ; 604/307;
604/501 |
Current CPC
Class: |
A61N 1/0476 20130101;
A61N 1/044 20130101; A61M 37/00 20130101; A61B 2018/1467 20130101;
A61B 18/14 20130101; A61B 2018/1861 20130101; A61B 2018/00452
20130101; A61N 1/306 20130101; A61N 1/0424 20130101; A61N 1/327
20130101; A61B 2018/00208 20130101 |
Class at
Publication: |
604/20 ; 604/307;
604/501 |
International
Class: |
A61N 1/30 20060101
A61N001/30; A61F 13/02 20060101 A61F013/02 |
Claims
1-124. (canceled)
125. Apparatus for facilitating delivery of a substance through
skin of a subject, comprising: a handle; and a cartridge, removably
coupled to the handle, the cartridge comprising one or more
electrodes and a patch comprising the substance, the electrodes
adapted to be applied to a region of the skin, and the patch
adapted to be applied to at least a portion of the region of the
skin by removal of the electrodes therefrom.
126. Apparatus according to claim 125, wherein the electrodes are
adapted, when a current is applied therethrough, to create at least
one micro-channel in stratum corneum epidermidis of the skin.
127. Apparatus according to claim 125, wherein the substance
includes a drug, and wherein the apparatus is adapted to facilitate
delivery of the drug through the skin of the subject.
128. Apparatus according to claim 125, wherein at least one of the
electrodes is adapted to contact the skin to create a contact area
therewith having a characteristic diameter of less than about 200
microns.
129. Apparatus according to claim 125, wherein the cartridge is
adapted to comprise only a single dose of the substance.
130. Apparatus according to claim 125, wherein the cartridge
comprises an electrical connector, adapted to electrically couple
the cartridge to the handle.
131. Apparatus according to claim 125, wherein the electrodes are
adapted, when a current is applied therethrough, to ablate stratum
corneum of the skin.
132. Apparatus according to claim 125, wherein the patch comprises
an adhesive strip on a skin-contact surface thereof, the adhesive
adapted to adhere to the skin of the subject at a time when the one
or more electrodes are applied to the region of the skin.
133. Apparatus according to claim 125, wherein the patch comprises:
a protective covering, which comprises a tab coupled to the
cartridge; and a pad comprising the substance, the pad adapted to
be brought into contact with at least a portion of the skin when
the tab is pulled.
134. Apparatus according to claim 125, wherein the cartridge
comprises a coupling mechanism, adapted to lock the cartridge to
the handle when the handle and cartridge are brought into contact
with one another.
135. Apparatus according to claim 125, wherein the handle comprises
a status indicator that is adapted to indicate to a user of the
apparatus to remove the electrodes from the region of the skin,
thereby applying the patch to the portion of the region.
136. Apparatus according to claim 125, wherein the handle comprises
a coupling mechanism, adapted to lock the cartridge to the handle
when the handle and cartridge are brought into contact with one
another.
137. Apparatus according to claim 136, wherein the handle comprises
a switch, and wherein the apparatus is adapted to allow coupling of
the cartridge to the handle only when the switch is activated.
138. Apparatus according to claim 136, wherein the cartridge
comprises at least one support, and wherein the handle is shaped to
define a slot therein, adapted to receive and be coupled to the
support.
139. Apparatus according to claim 125, wherein the cartridge is
adapted so that a ratio of a total contact area of the electrodes
with the skin to an area of the region of the skin is less than
about 1:20.
140. Apparatus according to claim 139, wherein the cartridge is
adapted so that the ratio is less than about 1:200.
141. Apparatus for facilitating delivery of a substance through
skin of a subject, comprising a patch assembly having a first
portion and a second portion adjacent to the first portion, the
first portion comprising a frame that surrounds an open portion of
the patch assembly, such that a region of the skin is exposed
through the open portion when the first portion is placed on the
skin, and the second portion comprising a pad comprising the
substance, the pad being adapted to be brought into contact,
through the open portion, with at least a portion of the region of
the skin.
142. Apparatus according to claim 141, wherein the frame comprises
an adhesive on a skin-contact surface thereof, the adhesive adapted
to adhere to the skin of the subject.
143. Apparatus according to claim 141, wherein the second portion
comprises a protective covering, which comprises a tab, and wherein
the pad is adapted to be brought into contact with the portion of
the skin when the tab is pulled.
144. Apparatus according to claim 141, wherein the first and second
portions are adapted to articulate at respective edges coupling the
portions.
145. A method for facilitating delivery of a substance contained in
a patch through skin of a subject, comprising: removably coupling,
to a handle, a cartridge comprising a plurality of electrodes;
placing at least a portion of the cartridge over the skin so that
at least a portion of the electrodes are applied to a region of the
skin; driving a current between two or more of the electrodes; and
applying the patch to at least a portion of the region of the skin
by removing the electrodes from the region of the skin.
146. A method according to claim 145, wherein driving the current
comprises driving the current so as to create at least one
micro-channel in stratum corneum epidermidis of the skin.
147. A method according to claim 145, wherein the substance
includes a drug, and wherein applying the patch comprises applying
the patch so as to deliver the substance through the skin.
148. A method according to claim 145, wherein placing at least a
portion of the cartridge over the skin comprises placing at least a
portion of the cartridge over the skin so that at least one of the
electrodes is brought in contact with the skin so as to create a
contact area therewith having a characteristic diameter of less
than about 100 microns.
149. A method according to claim 145, comprising electrically
coupling the cartridge to the handle.
150. A method according to claim 145, wherein driving the current
comprises driving a current configured to ablate stratum corneum of
the skin.
151. A method according to claim 145, wherein removably coupling
the cartridge to the handle comprises locking the cartridge to the
handle.
152. A method according to claim 145, wherein removably coupling
the cartridge to the handle comprises activating a switch that
allows the cartridge to be coupled to the handle.
153. A method according to claim 145, wherein placing at least a
portion of the cartridge over the skin comprises placing at least a
portion of the cartridge over the skin so that a ratio of a total
contact area of the electrodes with the skin to an area of the
region of the skin covered by the cartridge is less than about
1:20.
154. A method according to claim 153, wherein placing at least a
portion of the cartridge over the skin comprises placing at least a
portion of the cartridge over the skin so that the ratio is less
than about 1:200.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority from U.S. Provisional
Patent Application 60/374,224, filed Apr. 19, 2002, entitled,
"Rotary handheld transdermal drug delivery and analyte extraction,"
which is assigned to the assignee of the present patent application
and incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to methods and
devices for drug delivery and analyte extraction, and specifically
to medical methods and devices for puncturing the outer layer of
living skin and to methods and devices for transdermal transport of
a substance.
BACKGROUND OF THE INVENTION
[0003] A number of different methods have been developed to perform
transdermal drug delivery and/or analyte extraction, including
passive diffusion of a drug or analyte between a skin patch and
skin, as well as active processes such as iontophoresis,
sonophoresis, electroporation, and chemically enhanced diffusion.
These methods are primarily used for generating transdermal
movement of small molecules, but generally do not enhance the
motion of large molecules through the 10-50 micron thick outermost
layer of the skin, the stratum corneum epidermidis.
[0004] PCT Publication WO 97/07734 describes thermal ablation of
the stratum corneum using an electrically resistive element in
contact with the stratum corneum, such that a high current through
the element causes a general heating of tissue in its vicinity,
most particularly the stratum corneum.
[0005] U.S. Pat. No. 5,019,034 to Weaver et al., whose disclosure
is incorporated herein by reference, describes apparatus for
applying high voltage, short duration electrical pulses on the skin
to produce electroporation, and states that " . . . reversible
electrical breakdown . . . along with an enhanced tissue
permeability, is the characteristic effect of electroporation."
[0006] U.S. Pat. Nos. 5,885,211, 6,022,316, 6,142,939 and 6,173,202
to Eppstein et al., which are incorporated herein by reference,
describe methods for forming micropores in the stratum corneum by
heating tissue-bound water above the vapor point with a heat
conducting element, so as to enhance transdermal transport of an
analyte or active substance. Further enhancement techniques include
the use of sonic energy, pressure, and chemical enhancers.
[0007] U.S. Pat. No. 5,688,233 to Hofmann et al., which is
incorporated herein by reference, describes a method of transdermal
molecular delivery including providing molecules to be delivered
mixed with particles, contacting a selected area of a skin surface
with the particles and molecules, applying a pulsed electric field
of sufficient amplitude and duration to induce dielectric breakdown
of the stratum corneum, and applying a pressure to the molecules to
force transport of the molecules through the pores in the stratum
corneum into the underlying skin.
[0008] U.S. Pat. No. 5,318,514 to Hofmann, which is incorporated
herein by reference, describes an apparatus for implanting
macromolecules such as genes, DNA or pharmaceuticals into a
preselected surface tissue region of a patient. An applicator
having a plurality of electrodes is provided for contacting a
surface tissue region of a patient. A mechanism associated with the
applicator delivers a predetermined quantity of a fluid medium
carrying the preselected macromolecules. A signal generator is
provided for generating a predetermined electric signal. The
electrodes of the applicator are connected to the signal generator
for applying an electric field in the surface tissue region. The
field has a predetermined strength and duration in order to make
the walls of a plurality of cells in the surface tissue region
transiently permeable to permit the macromolecules to enter said
preselected cells without damaging said cells. This technique is
described as enhancing the uptake of macromolecules and thus
enhancing the therapeutic effect achieved.
[0009] U.S. Pat. No. 5,462,520 to Hofmann, which is incorporated
herein by reference, describes a method of transtissue molecular
delivery that includes encapsulating molecules to be delivered in a
microbubble carrier, contacting a selected area of a tissue surface
with a solution of the encapsulated molecules, and applying an
electric field of sufficient amplitude to induce electrofusion
between the tissue and the membrane of the microbubble.
[0010] U.S. Pat. No. 5,464,386 to Hofmann, which is incorporated
herein by reference, describes a method of transdermal molecular
delivery that includes encapsulating molecules to be delivered in a
vesicle, contacting a selected area of a tissue surface with a
solution of the vesicles, and applying a pulsed electric field of
sufficient amplitude to induce dielectric breakdown of the stratum
corneum and to induce transport of the intact vesicle through the
pores in the stratum corneum into the underlying tissue to enable
diffusion of molecules into the tissue.
[0011] U.S. Pat. Nos. 3,964,482 to Gerstel, 6,050,988 to Zuck, and
6,083,196 to Trautman et al., which are incorporated herein by
reference, describe other apparatus and methods for facilitating
transdermal movement of a substance.
[0012] U.S. Pat. No. 6,148,232 to Avrahami, which is assigned to
the assignee of the present patent application and is incorporated
herein by reference, describes apparatus for applying electrodes at
respective points on skin of a subject and applying electrical
energy between two or more of the electrodes to cause cell heating
and subsequent ablation of the stratum corneum primarily in areas
near the respective points. Various techniques for limiting
ablation primarily to the stratum corneum are described, including
spacing of the electrodes and monitoring the electrical resistance
of skin between adjacent electrodes.
[0013] Electrosurgery is commonly used during surgical procedures
today, particularly in endoscopic and laparoscopic surgery where
direct access to the tissue being dissected is limited.
Electrosurgery involves applying radio frequency electric current
to electrodes which are used to sever tissue or achieve
homeostasis. A publication entitled "Instruction Manual for the
Force 2 Electrosurgical Generator" (Valleylab/Tyco Healthcare Group
LP, Boulder, Colo.), which is incorporated herein by reference,
describes the modes of operation of electrosurgical devices.
[0014] U.S. Pat. No. 6,159,194 to Eggers et al., which is
incorporated herein by reference, describes electrosurgical
apparatus and methods for inducing tissue contraction, without
ablation or dissociation of surrounding tissue, in order to reduce
wrinkles in skin.
[0015] U.S. Pat. Nos. 6,066,134 and 6,024,733 to Eggers et al.,
which are incorporated herein by reference, describe
electrosurgical apparatus and methods for ablating outer layers of
skin for the treatment of unwanted tissue pigmentations, melanomas,
and other skin disorders.
[0016] U.S. Pat. No. 6,090,106 to Goble et al., which is
incorporated herein by reference, describes monopolar and bipolar
electrosurgical instruments for ablating gross tissue, such as the
prostate or endometrial tissue.
[0017] U.S. Pat. No. 4,943,290 to Rexroth et al., which is
incorporated herein by reference, describes electrosurgical
apparatus in which a nonconductive fluid is transported to the
region of an electrode in order to isolate the electrode and
prevent undesirable damage of surrounding tissue.
[0018] PCT Publication WO 02/085451 to Avrahami et al., and the
corresponding U.S. patent application Ser. No. 09/840,522, which
are incorporated herein by reference, describe a skin treatment
device that includes a plurality of electrodes, which are adapted
to be placed in contact with the skin and then moved across the
skin while maintaining electrical contact with the skin. The device
additionally includes a power source, which is adapted to apply a
current between two or more of the plurality of electrodes at the
same time as the electrodes are being moved across the skin.
[0019] PCT Publication WO 02/091934 to Avrahami et al., and the
corresponding U.S. patent application Ser. No. 09/859,645, which
are incorporated herein by reference, describe a device for
facilitating transdermal passage of a substance through skin on the
body of a subject. The device preferably includes an electrode and
a control unit. In a preferred embodiment, the control unit is
adapted to drive the electrode to apply to the skin a current
capable of ablating stratum corneum epidermidis of the skin, so as
to facilitate transdermal passage of the substance. The control
unit detects generation of at least one spark responsive to
application of the current, and modifies a parameter of the current
responsive to detecting the generation of the at least one
spark.
SUMMARY OF THE INVENTION
[0020] In some preferred embodiments of the present invention, a
handheld device for facilitating transdermal transport of a
substance, such as a drug, comprises (a) a plurality of ablation
electrodes, which are to be placed in contact with skin of a
subject, (b) a plurality of electrically-conductive contact pads,
each contact pad electrically coupled to one or more of the
ablation electrodes, (c) one or more driving electrodes, (c) a
handle, and (d) a control unit, adapted to apply current to the
driving electrodes, and to rotate the driving electrodes so as to
cause them to intermittently come in contact with each contact pad,
thereby causing the ablation electrodes coupled to that contact pad
to drive the current into the skin. As a result, at least one
micro-channel is created in the stratum corneum of the skin,
enabling or augmenting transdermal transport of the substance.
Preferably, the handheld device comprises a motor for rotating the
driving electrodes, and the driving electrodes comprise brush
electrodes.
[0021] In some preferred embodiments of the present invention, the
handheld device comprises an electrode board, which is mechanically
and preferably removably coupled to the handle. The upper surface
of the electrode board comprises the contact pads, and the lower
surface of the electrode board comprises the ablation electrodes.
Preferably, but not necessarily, each contact pad is electrically
coupled to a plurality (e.g., four) of the ablation electrodes. The
electrode board is typically discarded after a single use.
[0022] In other preferred embodiments of the present invention, the
handheld device comprises a contact board, which is mechanically
coupled to the handle. The lower surface of the contact board
comprises contact board contacts, and the upper surface of the
contact board comprises the contact pads, each of which is
electrically coupled to at least one of the contact board contacts.
The handheld device further comprises an electrode cartridge, which
is removably coupled to the handheld device. The lower surface of
the electrode cartridge comprises a plurality of ablation
electrodes, which are held in a vicinity of the skin of the
subject. The upper surface of the electrode cartridge comprises
cartridge contacts, each of which is electrically coupled to at
least one of the ablation electrodes, preferably to a plurality
(e.g., 2-10) of the ablation electrodes. When the electrode
cartridge is coupled to the handheld device, the cartridge contacts
make electrical contact with the contact board contacts. As a
result, when a driving electrode makes contact with a contact pad,
a current is driven (a) from the driving electrode, (b) to the
contact pad, (c) to at least one contact board contact, (d) to at
least one cartridge contact, (e) to at least one ablation
electrode, and (f) into the skin of the subject. Preferably, the
electrode cartridge is discarded after a single use.
[0023] In some preferred embodiments of the present invention, the
handheld device comprises a rotation assembly, which comprises a
rotational energy applicator, such as a motor or a manual crank.
For some applications, the rotation assembly comprises a support
element, such as a manifold, comprising the driving electrodes.
Alternatively, the rotation assembly comprises a rotating disk that
is driven by a driving gear, the disk comprising the driving
electrodes and being configured such that the driving electrodes
are arranged in one or more generally radial lines on the disk.
Preferably, the rotation assembly comprises a position sensor,
which monitors the motion of the support element or the rotating
disk, as the case may be, so as to facilitate the controlled
ablation by some or all of the ablation electrodes of stratum
corneum in contact therewith.
[0024] In some preferred embodiments of the present invention, the
electrode board or contact board, as the case may be, comprises a
printed circuit board (PCB), preferably a multi-layered PCB.
Contact pads on the upper surface of the PCB are electrically
coupled to at least one contact board contact or ablation
electrode, as the case may be, over one or more traces, as is known
in the art of PCB design and fabrication. The use of a PCB,
particularly a multi-layered PCB, allows contact board contacts or
ablation electrodes, as the case may be, to be readily placed at
locations other than in the vicinity of the respective contact pads
to which they are electrically coupled.
[0025] In some preferred embodiments of the present invention, the
handheld device comprises a plurality of power tracks, e.g., three,
on the electrode board or contact board, as the case may be,
preferably corresponding to the number of contact pads in each line
extending radially from the center of the electrode board or
contact board. The power tracks are coupled by power transfer
elements to the contact pads. A first end of each power transfer
element comprises a track contact, which comes in electrical
contact with the power tracks as the power transfer element
rotates. A second end of each power transfer element comprises a
driving electrode, which comes in electrical contact with at least
a portion of the contact pads as the power transfer element
rotates. For some applications, each power transfer element is a
shaped piece of metal, one end of which (defining the track
contact) is brought into electrical contact with the power track,
and the other end of which (defining the driving electrode) is
brought into electrical contact with the contact pads. Typically,
but not necessarily, only one power transfer element is in contact
with a given power track at any time, and the control unit only
applies power to one power track at a time.
[0026] In some embodiments of the present invention, the PCB
comprises at least two non-conducting layers, an upper
non-conducting layer and a lower non-conducting layer, which are
separated by a conducting layer. Contact pads on the upper
non-conducting layer are electrically coupled to electrodes or
contact board contacts mounted on the skin-facing side of the lower
non-conducting layer. The conducting layer serves as a ground, by
virtue of being electrically coupled to a negative terminal of the
power unit. A capacitive element is naturally formed by the lower
non-conducting layer separating the conducting layer and the
contact board contacts or electrodes. Therefore, handheld devices
that comprise this PCB assembly preferably do not comprise a return
electrode, in contact with the skin, that is specifically
designated to function as a ground. Instead, all of the ablation
electrodes or contact board contacts, as the case may be,
preferably "see" a small capacitance to ground, such that current
injected through one of the ablation electrodes or contact board
contacts sees a relatively-low resistance to ground via the
capacitive coupling to ground provided by the other electrodes in
this configuration.
[0027] In some preferred embodiments of the present invention, the
handheld devices comprise electrode sets comprising at least two
wires, which are bent and crossed with one another at about the
middle of each wire, such that the ends of the wires substantially
form a plane. Preferably, cone- or pyramid-style pieces (or pieces
having other shapes) surround and support the ends of the wires, a
portion of which protrude from the pieces and function as the
ablation electrodes. The point defined by the intersection of the
wires of the electrode set is brought in electrical contact with a
contact board contact. Alternatively, a coupling member,
electrically coupled to and in contact with the intersection point,
is brought in electrical contact with a contact board contact.
Preferably, the wires of the electrode set are shaped so as to
define an angular bend, such as a crimp or a 90 degree bend, as
they pass through the cone- or pyramid-style piece, in order to
enhance the friction effect holding the wires in place in the
pieces. Typically, the wires have a diameter less than about 150
microns.
[0028] In some preferred embodiments, electrodes are activated in
an activation sequence pursuant to which the distances between each
activated electrode and the successively activated electrode are
generally greater than such distances would be pursuant to a random
activation sequence. Larger distances between
successively-activated electrodes generally minimizes any sensation
of pain or discomfort that a subject might experience during
ablation. For some applications, an activation sequence is
generated by dividing an area including ablation electrodes into
regions, such as rectangular regions, arranged in a grid, each
region containing a plurality of electrodes. A sequence of regions
is determined such that sequential regions are at least a minimum
threshold distance apart. During ablation, the device cycles
through the regions, so that sequentially-activated regions are
generally at least a minimum threshold distance apart, and
activates an electrode in each region. The sequence is typically
cycled through at least twice, with a different electrode in each
region preferably activated each time the sequence is repeated.
Since sequential regions are at least the minimum threshold
distance apart, each electrode within a region is at least the
minimum threshold distance apart from the electrode activated in
the next region in the sequence. Therefore, the sequence of
activating electrodes within a given region during successive
cycles of the sequence is generally not important, which affords
flexibility in designing a contact board. In a preferred
embodiment, sequential regions are at least the distance of a
"knight's jump" (as in a game of chess) from one another, or are
separated by at least one intervening region. The sequence is
preferably configured to attempt to maximize both the average
distance between sequentially activated electrodes and the minimum
distance between sequentially activated electrodes.
[0029] When forming micro-channels in the stratum corneum, it is
generally desirable to apply the minimum energy necessary to
successfully form the micro-channels. Minimizing the applied energy
reduces device energy requirements, which is particularly
beneficial for battery-operated devices. Applying less energy may
also reduce any sensation a subject might feel during ablation.
While an appropriate voltage to apply can be pre-configured in an
ablation device, it is desirable in some applications to calibrate
the applied voltage at least once per use of the device. Such
repeated calibration is beneficial because the impedance of stratum
corneum varies from subject to subject, and even from time to time
within a given subject (for example, because of varying moisture
levels of the stratum corneum). Furthermore, for some applications,
it is desirable to separately calibrate the applied voltage for
many of the ablation electrodes or for each ablation electrode in
an array of electrodes, because the impedance of stratum corneum
sometimes varies even over a small area of skin.
[0030] In some preferred embodiments of the present invention, this
calibration is performed using a technique of "feed-forward," as
follows. A set of ablation electrodes is applied to the skin of the
subject. Using at least one ablation electrode, a brief calibration
burst of energy is applied to the stratum corneum. The calibration
burst is applied at a relatively low energy level (e.g., a low
voltage or a low current), such that ablation substantially does
not occur, and no sensation is typically felt by the subject. A
parameter of the calibration burst (e.g., current or voltage),
generally indicative of a level of impedance in the stratum
corneum, is measured. Responsive to the measured parameter, an
appropriate energy level, such as a voltage or a current, to use
for subsequent ablation is determined. Ablation is then performed
using this energy level.
[0031] In some preferred embodiments, the handheld devices
described herein comprise a pressure-sensing mechanism, adapted to
provide an indication that firm contact has been made between an
electrode cartridge and skin of the subject, responsive to which
indication an ablation procedure is begun. The pressure-sensing
mechanism preferably comprises a floating element, coupled to the
handle of the handheld device by a pivot joint, which allows the
floating element to pivot. A contact board is fixed to the lower
surface of the floating element. The electrode cartridge is
removably coupled to the contact board using snaps, which are
adapted to prevent the electrode cartridge from separating from the
contact board (as would otherwise typically occur because of
gravity), while generally not applying any upward pressure on the
electrode cartridge. A spring coupled to the handle applies
downward pressure on the floating element. When the electrode
cartridge is brought in contact with the skin, and downward
pressure is applied using the handle, the floating element is
pushed upward, activating a switch on the floating element, thereby
indicating that firm contact has been made between the electrode
cartridge and the skin. Alternatively, the pressure-sensing
mechanism comprises a force-detecting spring, such as a force
transducer, instead of lower and upper contacts.
[0032] In some preferred embodiments of the present invention,
packaging is provided for storing an electrode-containing element,
such as an electrode cartridge or an electrode board. The packaging
comprises a container, preferably comprising blister packaging, as
is known in the art. The container is typically shaped so as to
define an indentation, adapted to store the electrode-containing
element. To close the packaging and maintain cleanliness of the
electrode-containing element prior to use, the container is covered
with a removable covering. The indentation is positioned so that,
when the electrode-containing element is seated in the indentation,
the plane formed by the electrodes of the electrode-containing
element and the plane formed by the covering form an angle of
between 5 and 90 degrees, preferably between about 10 and 35
degrees. The angle is preferably configured to facilitate easy
grasping of the handle by a user while using the handle to remove
the electrode-containing element.
[0033] In order to attach the electrode-containing element to the
handle of the handheld device (or contact board of the handheld
device, as the case may be), the covering is removed by the user.
The handle is inserted into an open area of the packaging and
brought in contact with the top of the electrode-containing
element. Pressure is preferably applied, which couples the handle
to the electrode-containing element. The handle is then removed
from the packaging.
[0034] In some preferred embodiments of the present invention, a
patch, which is to be placed on the skin, comprises a plurality of
ablation electrodes and, optionally, at least one return electrode.
A handheld unit comprises a control unit coupled to provide power
to at least one driving electrode, which, in turn, is adapted to
drive one or more of the ablation electrodes upon electrical
contact therewith, as the handheld unit is moved over the patch.
Preferably, at any given time, only one of the driving electrodes
is activated as the handheld unit is passed over the patch, so only
some of the ablation electrodes are activated in a given pass.
Thus, multiple passes of the handheld unit are typically utilized
in order to activate all of the ablation electrodes. In this
manner, the instantaneous power requirements of the device are
reduced, and sensations felt by the patient are minimized during
treatment.
[0035] In other preferred embodiments, the handheld unit comprises
a driving mechanism such as a belt, which is disposed around two
cylinders. The handheld unit further comprises a motor, coupled to
one of the cylinders, and adapted to rotate the cylinder so as to
cause movement of the belt and of the driving electrodes. As the
driving electrodes pass over the patch, the driving electrodes make
electrical contact with a portion of the ablation electrodes. For
some applications, only some of the ablation electrodes are
activated in a single pass of the driving electrodes, such that
multiple passes of the driving electrodes are utilized in order to
activate the ablation electrodes.
[0036] Some embodiments of the present invention incorporate
methods and apparatus described in U.S. patent application Ser. No.
09/859,645 to Avrahami and Sohn, filed May 17, 2001, entitled,
"Monopolar and bipolar current application for transdermal drug
delivery and analyte extraction," which is assigned to the assignee
of the present patent application and incorporated herein by
reference. For example, the '645 application describes maintaining
the ablation electrodes either in contact with the skin, or up to a
distance of about 500 microns therefrom. The '645 application
further describes ablation of the stratum corneum by applying a
field having a frequency between about 10 kHz and 4000 kHz,
preferably between about 10 kHz and 500 kHz.
[0037] Alternatively or additionally, preferred embodiments of the
present invention incorporate methods and apparatus described in
U.S. patent application Ser. No. 09/840,522 to Avrahami and Sohn,
filed Apr. 23, 2001, entitled, "Handheld apparatus and method for
transdermal drug delivery and analyte extraction," which is
assigned to the assignee of the present patent application and
incorporated herein by reference. Still further alternatively or
additionally, preferred embodiments of the present invention
incorporate methods and apparatus described in the above-cited U.S.
Pat. No. 6,148,232 to Avrahami.
[0038] The term "micro-channel" as used in the context of the
present patent application refers to a pathway generally extending
from the surface of the skin through all or a significant part of
the stratum corneum, through which pathway molecules can diffuse.
Preferably, micro-channels allow the diffusion therethrough of
large molecules at a greater rate than the same molecules would
diffuse through pores generated by electroporation. Micro-channels
are typically about 30-150 microns in diameter, and typically
extend about 20-200 microns into the skin.
[0039] In some preferred embodiments of the present invention,
ablation is performed using an array of electrodes, preferably
closely-spaced electrodes, which act together to produce a high
micro-channel density in an area of the skin under the cartridge.
Typically, however, the overall area of micro-channels generated in
the stratum corneum is small compared to the total area covered by
the electrode array.
[0040] For some applications, a user applies the device to himself,
in which case the "user" and the "subject," as used herein, are the
same person.
[0041] In some embodiments of the present invention, one or more of
the ablation electrodes serve as return electrodes. Preferably,
these return ablation electrodes collectively have a relatively
large contact surface area with the skin, resulting in relatively
low current densities in the skin near the return ablation
electrodes, and thus no significant heating or substantial damage
to the skin in this vicinity. In proximity to each ablation
electrode in the electrode array, by contrast, the high current
density of the applied field typically induces rapid heating and
ablation of the stratum corneum.
[0042] In some preferred embodiments of the present invention, the
handheld device comprises an output unit coupled to the control
unit, to enable the control unit to communicate pertinent
information to the user. Preferably, the information comprises some
or all of the following: [0043] the operational status of the
device, [0044] an indication following successful ablation of the
stratum corneum by the ablation electrodes, [0045] the number of
micro-channels formed in the current application of the device, and
[0046] the amount of skin surface treated by the device.
[0047] Preferably, the output unit comprises a display, such as an
LCD or LED. Alternatively or additionally, the output unit
comprises a speaker or buzzer, preferably enabled to convey some of
the information.
[0048] In some preferred embodiments, the handheld device ablates
the stratum corneum so as to prepare the skin for substance
delivery or analyte extraction by a separate substance delivery
unit or analyte extraction unit. For example, a standard skin patch
containing a drug could be applied to the region of skin ablated by
the handheld device. Because ablation of the stratum corneum as
provided by these embodiments typically produces essentially no
sensation, the handheld device preferably comprises means for
demarcating the region of skin prepared by the device. The
demarcation helps the user to place the drug delivery unit or
analyte extraction unit on the treated region of skin. For example,
the device may comprise an ink or dye reservoir and means for
delivering the ink or dye to the surface of the skin region which
was treated by the device. Alternatively or additionally,
techniques are used that are described in PCT Patent Application
PCT/IL02/00896 to Sohn, filed Nov. 7, 2002, entitled, "Integrated
transdermal drug delivery system," which is assigned to the
assignee of the present patent application and is incorporated
herein by reference.
[0049] In other preferred embodiments, the handheld device is used
both to prepare the skin for substance delivery and to deliver the
substance to the surface of the prepared skin. Preferably, the
handheld apparatus comprises a substance reservoir and means for
delivering the substance to the surface of the skin. For example, a
porous material may be placed between adjacent electrodes, and
coupled to the substance reservoir by a conduit such that the
substance can flow from the reservoir, through the porous material,
to the skin.
[0050] There is therefore provided, in accordance with an
embodiment of the present invention, apparatus for application to
skin of a subject, including:
[0051] a board having a first surface and a second surface, the
first surface including a plurality of ablation electrodes, which
are adapted to be applied to the skin, and the second surface
including one or more contact pads, each one of the contact pads
electrically coupled to at least one of the ablation
electrodes;
[0052] one or more driving electrodes;
[0053] an energy applicator, coupled to the driving electrodes, the
energy applicator adapted to pass the driving electrodes over the
contact pads;
[0054] a power source, adapted to drive a current [0055] from the
driving electrodes, [0056] to the contact pads, [0057] to the
ablation electrodes,
[0058] capable of ablating at least a portion of stratum corneum of
the skin in a vicinity of the ablation electrodes, so as to
facilitate transdermal transport of a substance.
[0059] In an embodiment, the energy applicator is adapted to pass
the driving electrodes over the contact pads such that at any given
time less than all of the driving electrodes are in electrical
contact with one or more of the contact pads.
[0060] The power source is typically adapted to selectively drive
the current to a subset of the driving electrodes.
[0061] For some applications, the energy applicator includes a
motor or a manual crank.
[0062] The power source is typically adapted to drive the current
such that skin layers beneath the stratum corneum are substantially
not ablated.
[0063] For some applications, the apparatus includes a marking
unit, adapted to apply a marking substance to the skin so as to
demarcate a region of the skin to which the current is applied.
Alternatively or additionally, the apparatus includes one or more
protrusive elements, adapted to press the skin so as to demarcate a
region of the skin to which the current is applied.
[0064] For some applications, at least one of the ablation
electrodes is adapted to be applied to the skin so as to create a
contact area having a characteristic length of between about 30 and
150 microns.
[0065] In an embodiment, the ablation electrodes include a
current-driving ablation electrode and two or more return
electrodes, and the power source is adapted to drive respective
currents between the current-driving ablation electrode and each of
the return electrodes.
[0066] For some applications, the plurality of ablation electrodes
includes at least 100 ablation electrodes.
[0067] In an embodiment, the power source includes a first terminal
and a second terminal, the first terminal adapted to be
electrically coupled in sequence to at least a portion of the
contact pads at least a portion of the time, and wherein the board
includes:
[0068] a conductive element, adapted to be electrically coupled to
the second terminal and substantially electrically isolated from
the contact pads; and
[0069] a dielectric having first and second dielectric surfaces
thereof, the first dielectric surface adapted to be coupled to the
conductive element and the second dielectric surface adapted to be
coupled to the ablation electrodes, such that, during a given
ablation application period, when the first terminal is in
electrical contact with a first set including one or more of the
contact pads, and the power source drives a current into the first
set, a second set including one or more of the ablation electrodes,
which are electrically isolated during the given ablation
application period from all of the contact pads in the first set,
function as a capacitive electrical return path for the current via
the dielectric to the second terminal.
[0070] For some applications, the board includes a printed circuit
board (PCB), and at least one of the ablation electrodes is coupled
to the first surface at a point on the first surface that is at
least 5 millimeters from at least one of the contact pads to which
the at least one of the ablation electrodes is electrically
coupled.
[0071] Alternatively or additionally, at least 25% of the ablation
electrodes are coupled to the first surface at respective points on
the first surface that are at least 3 millimeters from respective
contact pads to which the ablation electrodes are electrically
coupled.
[0072] The power source is typically adapted to drive the current
so as to facilitate transport of the substance through the skin
into a body of the subject. Alternatively or additionally, the
power source is adapted to drive the current so as to facilitate
transport of the substance through the skin from within a body of
the subject.
[0073] In an embodiment, one or more of the contact pads are
electrically coupled to respective pluralities of the ablation
electrodes. In this case, one or more of the contact pads are
typically electrically coupled to respective sets of at least four
of the ablation electrodes.
[0074] For some applications, the contact pads are arranged in
concentric circles on the second surface. In this case, the energy
applicator may be adapted to rotate the driving electrodes over the
contact pads.
[0075] In an embodiment, the apparatus includes a support element,
supporting the driving electrodes, and the energy applicator is
adapted to move the supporting element so as to pass the driving
electrodes over the contact pads. In this case, the apparatus
typically includes a position sensor, adapted to monitor a position
of the support element, and the power source is adapted to regulate
timing of the driving of the current responsive to the monitored
position. Alternatively or additionally, the support element is
adapted to be movably coupled to the board. In this case, the
support element may be adapted to be rotatably coupled to the
board, and the energy applicator may be adapted to rotate the
support element so as to pass the driving electrodes over the
contact pads. In an embodiment, the contact pads and the driving
electrodes are adapted to be arranged such that each of the contact
pads comes in contact with at least one of the driving electrodes
during a rotation of the support element.
[0076] For some applications, the apparatus includes:
[0077] a plurality of power tracks, wherein the power source is
adapted to supply power to the power tracks; and
[0078] one or more power transfer elements, each having a first end
and a second end, each of the power transfer elements
including:
[0079] one of the driving electrodes, disposed at the first end of
the power transfer element; and
[0080] a track contact, disposed at the second end of the power
transfer element, adapted to be in electrical contact with the one
of the driving electrodes and to be brought into contact with at
least one of the power tracks.
[0081] In an embodiment, each track contact is adapted to be
brought into contact in sequence with at least two of the power
tracks.
[0082] Typically, the power source is adapted to supply power, for
ablating stratum corneum, to less than all of the power tracks at
any given time.
[0083] In an embodiment, the power tracks are on the second surface
of the board. Alternatively or additionally, the power tracks are
disposed in concentric circles or has a shape of a partial arc.
[0084] For some applications, the power tracks are configured such
that at any given time, each of the power tracks is in electrical
contact with only one of the driving electrodes.
[0085] In an embodiment, the driving electrodes are configured such
that at any given position of the driving electrodes, less than all
of the driving electrodes are in electrical contact with a same one
of the power tracks. In this case, the driving electrodes may be
configured such that at a point in time during operation of the
apparatus, a plurality of the driving electrodes are in electrical
contact with different respective power tracks, and the power
source may be adapted to drive the current into less than all of
the plurality of the driving electrodes at the point in time.
[0086] There is also provided, in accordance with an embodiment of
the present invention, apparatus for application to skin of a
subject, including:
[0087] a contact board having a first contact board surface and a
second contact board surface, the first contact board surface
including one or more contact board contacts, and the second
contact board surface including one or more contact pads, each
contact pad electrically coupled to at least one of the contact
board contacts;
[0088] an electrode cartridge removably coupled to the contact
board, the electrode cartridge having a first cartridge surface and
a second cartridge surface, the first cartridge surface including a
plurality of ablation electrodes, which are adapted to be applied
to the skin, and the second cartridge surface including one or more
cartridge contacts, each cartridge contact electrically coupled to
at least one of the ablation electrodes, such that when the
electrode cartridge is coupled to the contact board, at least a
portion of the contact board contacts come into electrical contact
with at least a portion of the cartridge contacts;
[0089] one or more driving electrodes;
[0090] an energy applicator, coupled to the driving electrodes, the
energy applicator adapted to pass the driving electrodes over the
contact pads; and
[0091] a power source, adapted to drive a current [0092] from the
driving electrodes, [0093] to the contact pads, [0094] to the
contact board contacts, [0095] to the cartridge contacts, [0096] to
the ablation electrodes,
[0097] capable of ablating at least a portion of stratum corneum of
the skin in a vicinity of the ablation electrodes, so as to
facilitate transdermal transport of a substance.
[0098] In an embodiment, the energy applicator is adapted to pass
the driving electrodes over the contact pads such that at any given
time less than all of the driving electrodes are in electrical
contact with one or more of the contact pads.
[0099] Alternatively or additionally, the power source is adapted
to selectively drive the current to a subset of the driving
electrodes.
[0100] At least one of the ablation electrodes is typically adapted
to be applied to the skin so as to create a contact area having a
characteristic length of between about 10 and 100 microns.
[0101] In an embodiment, the electrode cartridge includes at least
one housing and at least one set of two or more wires coupled to
the housing, each wire having two ends and an intermediate portion,
the wires supported by the housing, bent and crossed with one
another at the intermediate portion of each wire, so that the
intermediate portions of the wires touch each other and so that all
of the ends of the wires substantially form a plane, the ends
configured to function as at least four of the ablation
electrodes.
[0102] In an embodiment, the intermediate portion of one of the
wires is configured to function as one of the cartridge contacts
and to be electrically coupled to one of the contact board
contacts. For some applications, the apparatus includes a coupling
member, adapted to electrically couple the intermediate portion of
one of the wires to one of the contact board contacts.
[0103] In an embodiment, the set includes exactly two wires.
[0104] Each wire typically has a shape generally like a staple, but
may have other shapes.
[0105] For some applications, each wire is adapted to be supported
by the housing by passing through the housing, and a portion of
each wire that passes through the housing is shaped so as to define
an angular bend within the housing.
[0106] In an embodiment, the electrode cartridge includes:
[0107] at least one housing;
[0108] at least one set of two or more wires coupled to the
housing, each wire having two ends and an intermediate portion, the
wires supported by the housing so as not to touch each other;
and
[0109] a coupling element, coupled to the intermediate portion of
each of the wires, so that all of the ends of the wires
substantially form a plane, the ends configured to function as at
least four of the ablation electrodes.
[0110] In an embodiment, the coupling element is configured to
function as one of the cartridge contacts and to be electrically
coupled to one of the contact board contacts.
[0111] In an embodiment, the apparatus includes:
[0112] a plurality of power tracks, wherein the power source is
adapted to supply power to the power tracks; and
[0113] one or more power transfer elements, each having a first end
and a second end, each of the power transfer elements
including:
[0114] one of the driving electrodes, disposed at the first end of
the power transfer element; and
[0115] a track contact, disposed at the second end of the power
transfer element, adapted to be in electrical contact with the one
of the driving electrodes and to be brought into contact with at
least one of the power tracks.
[0116] The power source is typically adapted to supply power, for
ablating stratum corneum, to less than all of the power tracks at
any given time. For some applications, the power tracks are on the
contact board.
[0117] There is further provided, in accordance with an embodiment
of the present invention, apparatus for application to skin of a
subject, including:
[0118] a board, having a first surface and a second surface, the
first surface including a plurality of conductors, adapted to be
brought in contact with the skin, and the second surface including
a plurality of contact pads, each of the contact pads electrically
coupled to at least one of the conductors;
[0119] a power unit, having a first terminal and a second terminal,
the first terminal adapted to be electrically coupled in sequence
to at least a portion of the contact pads at least a portion of the
time, the power unit adapted to drive a current from the contact
pads to the conductors, capable of ablating stratum corneum of the
skin in a vicinity of the conductors, so as to facilitate
transdermal transport of a substance;
[0120] a conductive element, adapted to be electrically coupled to
the second terminal and substantially electrically isolated from
the contact pads; and
[0121] a dielectric having first and second dielectric surfaces
thereof, the first dielectric surface adapted to be coupled to the
conductive element and the second dielectric surface adapted to be
coupled to the conductors, such that, during a given ablation
application period, when the first terminal is in electrical
contact with a first set including one or more of the contact pads,
and the power unit drives a current into the first set, a second
set including one or more of the conductors, which are electrically
isolated during the given ablation application period from all of
the contact pads in the first set, function as a capacitive
electrical return path for the current via the dielectric to the
second terminal.
[0122] The apparatus is typically arranged to produce an impedance
of the capacitive return path that is less than 5 kilo-ohms.
[0123] During any given ablation application period, the first set
typically includes exactly one contact pad.
[0124] During any given ablation application period, a ratio of a
number of contact pads in the first set to a number of conductors
in the second set is typically less than 1:1. For some
applications, the ratio is less than 1:20 or even less than
1:100.
[0125] There is still further provided, in accordance with an
embodiment of the present invention, apparatus including a housing
and a set of two or more wires coupled to the housing, each wire
having two ends and an intermediate portion, the wires supported by
the housing, bent and crossed with one another at the intermediate
portion of each wire, so that the intermediate portions of the
wires touch each other and so that all of the ends of the wires
substantially form a plane, the ends configured to function as
electrodes for ablating stratum corneum of skin of a subject when
applied to the skin.
[0126] There is yet further provided, in accordance with an
embodiment of the present invention, apparatus for ablating stratum
corneum, including:
[0127] a housing;
[0128] a set of two or more wires coupled to the housing, each wire
having two ends and an intermediate portion, the wires supported by
the housing so as not to touch each other; and
[0129] a coupling element, electrically coupled to the intermediate
portion of each of the wires, so that all of the ends of the wires
substantially form a plane, the ends configured to function as
electrodes for ablating stratum corneum of skin of a subject when
applied to the skin.
[0130] There is also provided, in accordance with an embodiment of
the present invention, a method for facilitating transport of a
substance through an area of skin of a subject, the area defining a
set of ablation sites, the method including driving current in a
sequence into more than one of the ablation sites, the current
being capable of ablating stratum corneum of the skin in the
ablation sites, so as to facilitate transdermal transport of the
substance, the sequence being configured such that, during
successive first, second, and third time periods the current is
driven into respective first, second, and third ones of the
ablation sites, the first ablation site being non-adjacent to the
second ablation site, and the second ablation site being
non-adjacent to the third ablation site.
[0131] Typically, driving the current in the sequence includes
configuring the sequence to generally maximize a minimum distance
between ablation sites into which current is driven during
successive time periods. Alternatively or additionally, a sum of
distances between temporally adjacent ones of the ablation sites
into which current is driven is typically greater than such sum
would be if the sequence is generated randomly.
[0132] For some applications, driving the current includes driving
the current during 10 successive time periods, the sequence being
configured such that a distance between successive sites of
application of the current during each of the periods is greater
than 1 mm, or even greater than 3 mm.
[0133] For some applications, driving the current includes driving
the current during at least 10 successive time periods into
respective ones of the ablation sites, the sequence being
configured such that, for each of the periods, during temporally
adjacent ones of the time periods, the current is driven into
non-adjacent ablation sites. In an embodiment, driving the current
includes configuring the current such that during the at least 10
successive time periods, none of the ablation sites into which
current is driven is adjacent to another one of the ablation sites
into which current is driven.
[0134] There is yet additionally provided, in accordance with an
embodiment of the present invention, apparatus for facilitating
transport of a substance through an area of skin of a subject, the
area defining a set of ablation sites, the apparatus including:
[0135] a plurality of electrodes, which are adapted to be placed in
contact with the area of the skin at the ablation sites; and
[0136] a control unit, adapted to drive, during successive first,
second, and third time periods, a current capable of ablating
stratum corneum of the skin to a first one, a second one, and a
third one of the electrodes, the first one of the electrodes being
non-adjacent to the second one of the electrodes, and the second
one of the electrodes being non-adjacent to the third one of the
electrodes, so as to facilitate transdermal transport of the
substance.
[0137] There is still additionally provided, in accordance with an
embodiment of the present invention, a method for facilitating
transport of a substance through skin of a subject, including:
[0138] applying calibration electrical energy between a first and a
second site on the skin, the calibration electrical energy
configured such that stratum corneum of the skin is substantially
not ablated;
[0139] measuring a parameter of the calibration electrical
energy;
[0140] determining, responsive to the measured parameter, a level
of ablating electrical energy capable of ablating stratum corneum
of the skin; and
[0141] applying the ablating electrical energy at the determined
level to at least a portion of the skin, so as to facilitate
transdermal transport of the substance.
[0142] In an embodiment:
[0143] applying the calibration electrical energy includes applying
the calibration electrical energy between a plurality of first
sites and a plurality of respective second sites,
[0144] measuring the parameter includes measuring the parameter
with respect to each of the first sites and the respective second
sites,
[0145] determining the level of ablating electrical energy includes
determining the level with respect to each of the first sites and
the respective second sites, and
[0146] applying the ablating electrical energy includes applying
the ablating electrical energy at the respective determined levels
at each of the respective first and second sites.
[0147] For some applications, applying the calibration electrical
energy includes applying the energy for less than 200
microseconds.
[0148] In an embodiment, applying the voltage drop includes setting
the voltage drop to be between about 50 and 100 volts. In this
case, measuring the parameter typically includes measuring a level
of a current flowing responsive to the voltage drop.
[0149] There is also provided, in accordance with an embodiment of
the present invention, apparatus for facilitating transport of a
substance through skin of a subject, including:
[0150] a plurality of electrodes, which are adapted to be placed in
contact with the skin; and
[0151] a control unit, adapted to:
[0152] apply calibration electrical energy between a first one and
a second one of the electrodes, the calibration electrical energy
configured such that stratum corneum of the skin is substantially
not ablated,
[0153] measure a parameter of the calibration electrical
energy,
[0154] determine, responsive to the measured parameter, a level of
ablating electrical energy capable of ablating stratum corneum of
the skin, and
[0155] apply the ablating electrical energy at the determined level
to at least a portion of the skin, using at least a portion of the
electrodes, so as to facilitate transdermal transport of the
substance.
[0156] There is further provided, in accordance with an embodiment
of the present invention, apparatus for application to skin of a
subject, including:
[0157] a handle;
[0158] an electrode cartridge including electrodes which are
adapted to be brought in contact with the skin;
[0159] a pivot joint coupled to the handle;
[0160] a floating element coupled to the handle by the pivot joint
and coupled to the electrode cartridge; and
[0161] a control unit, adapted to detect a displacement of the
floating element when force is applied to the electrode cartridge
by the skin, and, responsive thereto, to drive through the
electrodes current capable of ablating stratum corneum of the skin,
so as to facilitate transdermal transport of a substance.
[0162] For some applications, the apparatus includes a switch, and
the control unit is adapted to detect the displacement of the
floating element responsive to a change in state of the switch.
[0163] In an embodiment, the handle includes two or more snaps, and
the floating element is adapted to be removably coupled to the
electrode cartridge by the snaps. In this case, the snaps are
typically arranged to: (a) prevent the electrode cartridge from
separating from the floating element, and (b) avoid causing a
displacement of the floating element sufficient to cause the
control unit to drive current through the electrodes.
[0164] There is yet further provided, in accordance with an
embodiment of the present invention, packaging for storing an
electrode-containing element having a plurality of skin-contact
electrodes disposed on a skin-contact surface of the element so as
to substantially define a skin-contact plane, the packaging
including:
[0165] a removable cover, disposed so as to substantially define a
cover plane; and
[0166] a container, shaped so as to define an element indentation
therein, the element indentation having a bottom surface and shaped
to hold the electrode-containing element in a position such that
the cover plane and the skin-contact plane of the
electrode-containing element form an angle of greater than 5
degrees and less than 90 degrees when the electrode-containing
element is stored in the packaging.
[0167] In an embodiment, the angle is between about 10 and 35
degrees.
[0168] The container typically includes blister packaging.
[0169] For some applications, the container is shaped so as to
define a handle indentation therein, shaped so as to accept a
handle, and so as to guide the handle to accurately couple with the
electrode-containing element while the electrode-containing element
is in the element indentation.
[0170] There is still further provided, in accordance with an
embodiment of the present invention, apparatus for application to
skin of a subject, including:
[0171] a plurality of ablation electrodes, which are adapted to be
placed in contact with the skin so as to provide electrical contact
with the skin;
[0172] at least two driving electrodes, adapted to be passed across
the ablation electrodes, so as to create electrical contact between
respective ones of the driving electrodes and the ablation
electrodes; and
[0173] a power source, adapted to drive a first one of the driving
electrodes to apply current capable of ablating stratum corneum of
the skin to a first set of at least one of the ablation electrodes,
and to drive a second one of the driving electrodes to apply
current capable of ablating stratum corneum of the skin to a second
set of at least one of the ablation electrodes, so as to facilitate
transdermal transport of a substance.
[0174] For some applications, the power source is adapted to:
[0175] drive the first one of the driving electrodes to apply the
current capable of ablating stratum corneum to the first set of
ablation electrodes during a first pass of the driving electrodes
across the ablation electrodes, and
[0176] drive the second one of the driving electrodes to apply the
current capable of ablating stratum corneum to the second set of
ablation electrodes during a second pass of the driving electrodes
across the ablation electrodes.
[0177] In an embodiment, the driving electrodes are adapted to be
passed across the ablation electrodes so as to create electrical
contact with a first one of the ablation electrodes prior to
creating electrical contact with a second one of the ablation
electrodes.
[0178] In an embodiment, the apparatus includes a driving
mechanism, adapted to pass the driving electrodes across the
ablation electrodes. For example, the apparatus may include a belt,
adapted to be coupled to the driving mechanism, the belt including
the driving electrodes.
[0179] The present invention will be more fully understood from the
following detailed description of the preferred embodiments
thereof, taken together with the drawings in which:
BRIEF DESCRIPTION OF DRAWINGS
[0180] FIG. 1 is a schematic, sectional illustration of a handheld
device for facilitating transdermal transport of a substance, in
accordance with a preferred embodiment of the present
invention;
[0181] FIG. 2A is a schematic pictorial illustration of a handheld
device for facilitating transdermal transport of a substance, in
accordance with a preferred embodiment of the present
invention;
[0182] FIG. 2B is a schematic bottom-view of a portion of the
device of FIG. 2A, in accordance with a preferred embodiment of the
present invention;
[0183] FIG. 3A is a schematic, pictorial illustration of another
handheld device for facilitating transdermal transport of a
substance, in accordance with a preferred embodiment of the present
invention;
[0184] FIG. 3B is a schematic bottom-view of a portion of the
device of FIG. 3A, in accordance with a preferred embodiment of the
present invention;
[0185] FIG. 3C is a schematic bottom-view of another portion of the
device of FIG. 3A, in accordance with a preferred embodiment of the
present invention;
[0186] FIG. 3D is a schematic bottom-view of an alternative
embodiment of the portion of the device shown in FIG. 3B, in
accordance with a preferred embodiment of the present
invention;
[0187] FIG. 3E is a schematic, sectional side-view illustration of
an example electrical path through the device of FIG. 3A, in
accordance with a preferred embodiment of the present
invention;
[0188] FIG. 4A is a schematic, pictorial illustration of yet
another handheld device for facilitating transdermal transport of a
substance, in accordance with a preferred embodiment of the present
invention;
[0189] FIG. 4B is a schematic side-view illustration of a portion
of an alternative embodiment of the handheld device shown in FIG.
4A, in accordance with a preferred embodiment of the present
invention;
[0190] FIG. 4C is a schematic illustration of a power transfer
disk, in accordance with a preferred embodiment of the present
invention;
[0191] FIG. 5 is a schematic illustration of a rotation assembly,
in accordance with a preferred embodiment of the present
invention;
[0192] FIG. 6A is a schematic illustration of a printed circuit
board (PCB) for use with the devices shown in FIGS. 1, 2A, 3A, and
4A, in accordance with a preferred embodiment of the present
invention;
[0193] FIG. 6B is a schematic, sectional side-view of a portion of
the PCB of FIG. 6A, in accordance with a preferred embodiment of
the present invention;
[0194] FIG. 7A is a schematic sectional illustration of a PCB
assembly for use with the devices shown in FIGS. 1, 2A, 3A and 4A,
in accordance with a preferred embodiment of the present
invention;
[0195] FIG. 7B is a schematic illustration of a circuit
representing the PCB assembly of FIG. 7A, in accordance with a
preferred embodiment of the present invention;
[0196] FIGS. 8A and 8B are schematic illustrations of an electrode
set, in accordance with a preferred embodiment of the present
invention;
[0197] FIGS. 8C and 8D are schematic illustrations of another
electrode set, in accordance with a preferred embodiment of the
present invention;
[0198] FIG. 9 is a schematic sectional side-view illustration of a
portion of the electrode set of FIGS. 8A and 8B in electrical
contact with a contact board contact, in accordance with a
preferred embodiment of the present invention;
[0199] FIG. 10 is a schematic sectional illustration of a coupling
member electrically coupling the electrode set of FIGS. 8A and 8B
or FIGS. 8C and 8D to a contact board contact, in accordance with a
preferred embodiment of the present invention;
[0200] FIG. 11 is a schematic sectional illustration of an
electrode of the electrode set of FIGS. 8A and 8B, in accordance
with a preferred embodiment of the present invention;
[0201] FIG. 12 is a schematic illustration of a method for
sequencing the activation of electrodes, in accordance with a
preferred embodiment of the present invention;
[0202] FIG. 13 is a schematic illustration of a method for
generating an activation sequence, in accordance with a preferred
embodiment of the present invention;
[0203] FIG. 14 is a flow chart that schematically illustrates a
method for calibrating a voltage, in accordance with a preferred
embodiment of the present invention;
[0204] FIG. 15 is a schematic sectional illustration of a
pressure-sensing mechanism for use with the devices shown in FIGS.
1, 2A, 3A, and 4A, in accordance with a preferred embodiment of the
present invention;
[0205] FIG. 16 is a schematic sectional illustration of packaging
for storing an electrode-containing element, in accordance with a
preferred embodiment of the present invention;
[0206] FIGS. 17A and 17B are schematic illustrations of yet another
handheld device for facilitating transdermal transport of a
substance, in accordance with a preferred embodiment of the present
invention;
[0207] FIG. 18 is a schematic illustration of still another
handheld device for facilitating transdermal transport of a
substance, in accordance with a preferred embodiment of the present
invention; and
[0208] FIG. 19 is a schematic, partly sectional illustration of a
further handheld device for facilitating transdermal transport of a
substance, in accordance with a preferred embodiment of the present
invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0209] FIG. 1 is a schematic, sectional illustration of a handheld
device 100 for facilitating transdermal transport of a substance,
such as a drug, in accordance with a preferred embodiment of the
present invention. Device 100 preferably comprises a handle 130, a
power unit 102, a control unit 104, and a rotation assembly 114,
which is mechanically coupled to a plurality of ablation electrodes
112. Details of some rotation assemblies are described hereinbelow.
Although handles, such as handle 130, are shown in FIG. 1A and
other figures as elongated elements, this is for the sake of
illustration only; embodiments of the present invention include
other shapes. In addition, although handles, power units, and
control units are shown in the figures as incorporated in an
integrated unit, this is for the sake of illustration only. In some
embodiments of the present invention, power units and/or control
units are located external to handles and are coupled to handles
over wires or wirelessly.
[0210] Preferably, control unit 104 is electrically coupled to
rotation assembly 114 and ablation electrodes 112 by an electrical
bus 122, so as to drive a current through ablation electrodes 112.
The current is typically configured to cause current flow through
skin 150 of a subject or one or more sparks to occur between
ablation electrodes 112 and skin 150. Activation of device 100 is
initiated when a user activates a power switch 106, such as: (a) a
button, which is preferably located at a convenient position on
handle 130, or (b) using a switch, as described hereinbelow.
Preferably, handle 130 comprises a status indicator 108, such as a
status light, which informs the user of the status of device 100,
for example when the device is ready to commence electrical
treatment and/or when the electrical treatment has been completed.
Although applying electrical energy to ablation electrodes is
sometimes referred to herein as "applying a voltage," "applying a
voltage drop," or "applying a current," it is to be understood that
all of these techniques can be used for all applications, except
where the context clearly indicates otherwise.
[0211] In a preferred embodiment, regulation of the magnitude and
timing of the voltage applied to ablation electrodes 112 controls
the ablation of stratum corneum 151 of skin 150, so as to improve
transdermal delivery of a substance, such as a drug. Preferably, an
alternating voltage is applied to ablation electrodes 112,
typically having a frequency between about 10 kHz and 4000 kHz,
most preferably between about 50 kHz and 500 kHz.
[0212] For some applications, the voltage is applied for a fixed
length of time, determined in advance to be sufficient to achieve
the desired degree of ablation. Alternatively, electrical impedance
of the stratum corneum is continuously monitored, and a substantial
decrease is interpreted to indicate achievement of a desired level
of ablation, whereupon energy application is terminated.
[0213] Preferably, each one of ablation electrodes 112 has a
contact area with the skin characterized by a diameter of
approximately 10-150 microns, typically approximately 60-100
microns. It is noted that this contact area is significantly
smaller than that typically used for electroporation applications.
For some applications, ablation electrodes 112 function as
monopolar electrodes, whereby electrical energy is discharged from
ablation electrodes 112 into skin 150, while the return path of the
electrical current passes through a much larger surface area (e.g.,
a metal base surrounding or adjacent to ablation electrodes 112).
This typically results in a set of distinct and non-overlapping
ablated regions 134 near each ablation electrode 112, but
substantially no damage to tissue in other regions between the
various ablation electrodes. For example, each ablated area may
have a characteristic diameter of about 60-100 microns, and be
separated by a distance of about 700-1000 microns from adjacent
ablated areas. In a preferred embodiment, for an electrode array
which covers a total skin area A, the percentage of skin area A
which is ablated is less than about 5%, and is most preferably on
the order of about 0.5%.
[0214] Alternatively or additionally, when a larger number of
ablation electrodes 112 are included in device 100 (e.g., greater
than three, or greater than twenty), it is desirable for some
applications for one of ablation electrodes 112 to act as an
ablation electrode at a particular time, and for two or more of the
other electrodes to act, in combination, as non-ablating "return"
electrodes, each conveying a fraction of the ablating current back
to control unit 104. Further alternatively or additionally, two
relatively large return electrodes are provided, functioning as a
"split ground."
[0215] For some applications, the methods and apparatus of the
present invention are carried out in combination with other
techniques known in the art for ablating the stratum corneum, such
as those described in the above-cited PCT Publication WO 97/07734
to Eppstein et al.
[0216] For some applications, electrode cartridge 114 comprises an
inkpad 124, which marks the treated region of skin 150 such that a
substance-containing patch can be accurately and directly placed on
the electrically-treated region after the cartridge has been
removed from the region. Alternatively, electrode cartridge 114 has
an uneven lower surface, so as to leave temporary dimples on the
skin surrounding the treated region of skin 150, thereby
facilitating the accurate placement of a substance-containing
patch.
[0217] Reference is now made to FIGS. 2A and 2B. FIG. 2A is a
schematic, pictorial illustration of a handheld device 20 for
transdermal transport of a substance, such as a drug, in accordance
with a preferred embodiment of the present invention. FIG. 2B is a
schematic bottom-view of an electrode board 30 of handheld device
20, in accordance with a preferred embodiment of the present
invention. Except for differences described hereinbelow, device 20
is preferably configured to operate generally in accordance with
techniques described herein for ablating stratum corneum.
[0218] Device 20 comprises a rotation assembly 23, which comprises
a rotational energy applicator, such as a motor 22 or a manual
crank, to which is coupled a support element, such as a manifold
26, comprising a plurality of driving electrodes 28. Preferably,
driving electrodes 28 comprise brush electrodes. A position sensor
24, e.g., positioned adjacent to motor 22 and manifold 26,
typically monitors the motion of manifold 26, so as to facilitate
the controlled ablation of stratum corneum by ablation electrodes
41 (FIG. 2B) in contact therewith. A handle 131 of device 20 is
coupled, preferably removably, to electrode board 30, such as by
placing the handle over electrode board 30 and applying pressure on
the board from the handle. For some applications, the handle is
coupled to the board using clips, such as snaps 412, described
hereinbelow with reference to FIG. 15.
[0219] Preferably, electrode board 30 comprises an alignment pin 36
to assist in maintaining proper alignment of motor 22 and manifold
26 with electrode board 30. Electrode board 30 preferably further
comprises a plurality of contact pads 32, each of which is coupled,
through electrode board 30, via leads 34, to one or more ablation
electrodes 41 on the lower surface of electrode board 30 (FIG. 2B).
For simplicity, FIG. 2B shows the coupling of only one of contact
pads 32 to a set of four ablation electrodes 41, however it is to
be understood that typically each of the contact pads are coupled
to respective sets of one or more ablation electrodes 41. Although
leads 34 are shown as wires external to electrode board 30 in FIG.
2B, this is for clarity of illustration only; preferably the leads
are incorporated into electrode board 30. Additionally, although
only one manifold 26 and corresponding driving electrodes 28 are
shown in FIG. 2A, for some applications, a plurality of such
manifolds are incorporated into device 20. Ablation electrodes 41
are preferably arranged in a geometry, such as a square 42, that
produces an ablated area of the skin suitable for convenient
application or extraction of the substance, such as by using a
patch. Typically, square 42 has an area of between about 1 and 20
square centimeters.
[0220] When a driving electrode contacts a contact pad, and control
unit 104 drives power unit 102 (FIG. 1) to power driving electrodes
28 during such contact, the ablation electrodes electrically
coupled to that contact pad drive current into skin 150, thereby
creating micro-channels in the stratum corneum of the skin. For
some applications, all of ablation electrodes 41 are activated in a
single rotation of manifold 26.
[0221] In a preferred embodiment, electrode board 30 comprises on
the order of 1000 ablation electrodes 41, coupled in respective
sets of four electrodes to 250 contact pads 32. A smaller number of
electrodes 41 and pads 32 are shown in FIGS. 2A and 2B for clarity.
By arranging the pads radially outward from the center of electrode
board 30 and only having one manifold comprising driving
electrodes, only a small fraction of ablation electrodes 41 are
activated at any one time, thereby reducing the short-term current
requirements on power unit 102. In addition, less than all of
driving electrodes 28 may be activated at any given time, further
reducing the number of ablation electrodes 41 that are activated at
any one time. For example, when the 250 contact pads are divided
into 50 radial lines of 5 contact pads each, only 20 ablation
electrodes at any instant are typically activated out of the total
of 1000. Alternatively, providing driving electrodes 28 with an
angular offset, such that the driving electrodes do not fall along
a radial line from alignment pin 36, allows for only one contact
pad to be activated at a time. This reduces absolute power
requirements as well as sensation by the patient. Alternatively or
additionally, driving electrodes 28 are not all activated
simultaneously. Any one or more of these techniques typically
allows for rapid ablation of the skin, while maintaining sufficient
spacing between simultaneously-activated ablation electrodes, so as
to reduce sensation by the patient.
[0222] Reference is now made to FIGS. 3A, 3B, 3C and 3D. FIG. 3A is
a schematic, pictorial illustration of a handheld device 21 for
facilitating transdermal transport of a substance, such as a drug,
in accordance with a preferred embodiment of the present invention.
FIG. 3B is a schematic bottom-view of a contact board 230 of
handheld device 21, in accordance with a preferred embodiment of
the present invention. FIG. 3C is a schematic bottom-view of an
electrode cartridge 250 of handheld device 21, in accordance with a
preferred embodiment of the present invention. FIG. 3D is a
schematic bottom-view of an alternative embodiment of contact board
230 of handheld device 21, in accordance with a preferred
embodiment of the present invention. Except for differences
described hereinbelow, device 21 is preferably configured to
operate generally in accordance with techniques described herein
for ablating stratum corneum.
[0223] Device 21 comprises a rotation assembly 223, which comprises
a rotational energy applicator, such as a motor 222 or a manual
crank, to which is coupled a support element, such as a manifold
226, comprising a plurality of driving electrodes 228. Preferably,
driving electrodes 228 comprise brush electrodes. Preferably, a
position sensor 224, e.g., adjacent to motor 222 and manifold 226,
monitors the motion of manifold 226, so as to facilitate the
controlled ablation of stratum corneum by ablation electrodes 258
(FIG. 3C) in contact therewith. A handle 229 or other portion of
device 21 is coupled to contact board 230. Preferably, contact
board 230 comprises an alignment pin 236 to assist in attaining and
maintaining proper alignment of motor 222 and manifold 226 with
contact board 230. Contact board 230 preferably comprises a
plurality of contact pads 232, each of which is coupled via leads
234 to at least one contact board contact 239 on the lower surface
of contact board 230 (FIG. 3B). For simplicity, FIG. 3B shows the
coupling of only one of contact pads 232 to a set of four contact
board contacts 239. Although leads 234 are shown as wires external
to contact board 230 in FIG. 3B, this is for clarity of
illustration only; preferably, the leads are incorporated into
contact board 230.
[0224] Handheld device 21 further comprises electrode cartridge
250, which is typically discarded after a single use. Electrode
cartridge 250 is removably coupled to handheld device 21,
preferably by clipping the electrode cartridge to a lower surface
of handle 229 or to a lower surface of contact board 230, using
clips, such as snaps 412, described hereinbelow with reference to
FIG. 15. Preferably, electrode cartridge 250 comprises an alignment
pin 252 to assist in attaining and maintaining proper alignment of
the electrode cartridge with contact board 230, motor 222, and
manifold 226. The lower surface of electrode cartridge 250
comprises a plurality of ablation electrodes 258 (FIG. 3C), which
are placed against skin of the subject. The upper surface of
electrode cartridge 250 comprises a plurality of cartridge contacts
254, each of which is electrically coupled, through electrode
cartridge 250, to at least one of ablation electrodes 258,
preferably to a plurality (e.g., four) of the ablation
electrodes.
[0225] Ablation electrodes 258 are preferably arranged in a
geometry, such as a square 256 (FIG. 3C), that produces an ablated
area of the skin suitable for convenient application or extraction
of the substance, such as by using a patch. The area of square 256
is typically between about 1 and 20 square centimeters. Cartridge
contacts 254 (FIG. 3A) are preferably arranged in substantially the
same arrangement as the ablation electrodes, on the other side of
ablation cartridge 250, so that each cartridge contact 254
corresponds to and is located in a vicinity of one or more ablation
electrodes 258 (FIG. 3C). For the sake of illustration only, a
one-to-one correspondence between cartridge contacts 254 and
ablation electrodes 258 is shown in FIGS. 3A and 3C. The
arrangement of cartridge contacts 254 (FIG. 3A) and contact board
contacts 239 (FIG. 3B) are substantially the same, so as to enable
electrical contact between corresponding contacts when the lower
surface of contact board 230 and the upper surface of electrode
cartridge 250 are brought into contact with one another.
[0226] Although contact board contacts 239 are shown as arranged in
a square 238, the area of which is smaller than an area 231 (FIG.
3A) that encompasses contact pads 232, this is for the sake of
illustration only. For some applications, contact board contacts
239 are arranged in an arrangement, such as a square 240 (FIG. 3D),
the area of which is larger than area 231.
[0227] Reference is now made to FIG. 3E, which is a schematic,
sectional side-view illustration of an example electrical path
through handheld device 21, in accordance with a preferred
embodiment of the present invention. Current travels over the
following path from manifold 226 to skin 150: [0228] (a) current is
applied to driving electrode 228, a brush portion of which makes
physical and electrical contact with contact pad 232; [0229] (b)
contact pad 232 is electrically coupled to at least one contact
board contact 239, by at least one lead 234, which passes through
contact board 230; [0230] (c) contact board contact 239 makes
physical and electrical contact with cartridge contact 254, which
is electrically coupled to at least one ablation electrode 258, by
at least one lead 259, which passes through electrode cartridge
250; and [0231] (d) ablation electrode 258 applies the current to
skin 150.
[0232] In a preferred embodiment, electrode cartridge 250 comprises
on the order of 1000 ablation electrodes 258, coupled in respective
sets of four ablation electrodes to 250 electrode contacts 254. A
smaller number of ablation electrodes 258 and contact pads 232 are
shown in FIGS. 3A, 3B, 3C, and 3D for clarity.
[0233] FIGS. 4A, 4B, and 4C are schematic illustrations of a
handheld device 900 for enabling transdermal transport of a
substance, such as a drug, in accordance with a preferred
embodiment of the present invention. Handheld device 900 is
generally similar to handheld device 20, as described hereinabove
with reference to FIGS. 2A and 2B, and, except for differences
described hereinbelow, handheld device 900 is preferably configured
to operate generally in accordance with techniques described herein
for ablating stratum corneum, including with apparatus and
techniques described hereinabove with reference to FIGS. 3A, 3B,
3C, 3D and 3E. In particular, although handheld device 900 is
described hereinbelow as comprising an electrode board 818, for
some applications handheld device 900 instead comprises a contact
board and an electrode cartridge, as described hereinabove with
reference to FIGS. 3A, 3B, 3C, 3D and 3E.
[0234] FIG. 4A shows a particular preferred configuration for
bringing power to contact pads 32. In this configuration, electrode
board 818 (configuration shown) or the handle (configuration not
shown) comprises a plurality of power tracks 902, e.g., three or
four, preferably corresponding to the number of driving electrodes
912 and/or the number of contact pads 32 in each line extending
radially from pin 36. The power tracks are coupled by power
transfer elements 910 to contact pads 32. A first end of each power
transfer element 910 comprises one of track contacts 908, which
comes in electrical contact with power tracks 902 as the power
transfer element rotates. A second end of each power transfer
element 910 comprises one of driving electrodes 912, which comes in
electrical contact with at least a portion of contact pads 32 as
the power transfer element rotates. Track contacts 908 and driving
electrodes 912 preferably comprise brush electrodes. Although only
one power transfer element 910 is shown for clarity, three such
elements 910 are preferably coupled to each of one or more
rotational members 906 in the illustrated configuration.
Preferably, control unit 104 supplies power from power unit 102 to
less than all of power tracks 902 at a time, over power leads 914,
such that typically only one radial line of contact pads 32 is
activated at any given time. For some applications, power is
supplied to only one power track 902 at a time. For applications in
which handheld device 900 comprises the same number of driving
electrodes 912 as power tracks 902, control unit 104 typically
selectively actives contact pads 32 by powering the appropriate
power track at the appropriate time.
[0235] For some applications, power unit 102 and/or control unit
104 are fixed to electrode board 818 (configuration not shown), and
not to handle 130. For some applications, power tracks 902 are
fixed above rotational members 906 (and not to electrode board
818), but otherwise operate in substantially the same manner as
described hereinabove (configuration not shown).
[0236] FIG. 4B is a schematic side-view illustration of a portion
of an alternative embodiment of handheld device 900, in accordance
with a preferred embodiment of the present invention. FIG. 4C is a
schematic illustration of a power transfer disk 920, in accordance
with a preferred embodiment of the present invention. One or more
of control unit 104, power unit 102, and motor 22 are fixed to
electrode board 818, instead of to handle 130. Instead of
rotational members 906, handheld device 900 comprises power
transfer disk 920, which typically comprises gear teeth 922
arranged around the circumference of the power transfer disk. Motor
22, whether fixed to electrode board 818 or handle 130, engages
gear teeth 922 and drives rotation of the power transfer disk.
[0237] On its lower surface, power transfer disk 920 comprises a
plurality of power transfer elements 924. Each power transfer
element 924 typically comprises a track contact 926 at a first end
of the element, and at least one driving electrode 928 at a second
end of the element. Track contact 926 and driving electrode 928 of
each power transfer element are directly electrically connected to
each other, typically but not necessarily because each power
transfer element 924 is formed from a single piece of metal. Track
contact 926 is aligned so as to come in electrical contact with
power tracks 902 as the power transfer disk rotates. Each of
driving electrodes 928 is typically aligned to come in contact with
at least one contact pad 32 as the power transfer disk rotates. For
example, each of the driving electrodes may sequentially come in
contact with a respective plurality of contact pads 32, each
disposed at a certain distance from the center of the power
transfer disk. Thus, FIG. 4C shows track contact 926 of each power
transfer element 924 at a fixed radius from the center of the power
transfer disk, while driving electrodes 928 of each power transfer
element 924 are at different respective distances from the center
of the power transfer disk.
[0238] Control unit 104 drives motor 22 to rotate power transfer
disk 920, and typically selectively applies power to power tracks
902 based on the rotational position of the disk, so as to
selectively power contact pads 32.
[0239] FIG. 5 is a schematic illustration of a rotation assembly
820, in accordance with a preferred embodiment of the present
invention. Rotation assembly 820 is adapted to be used instead of
the rotation assemblies described hereinabove with reference to
FIGS. 2A, 3A and 4A. Rotation assembly 820 comprises a rotating
disk 826 that is rotationally driven by a driving gear 824,
preferably using friction or teeth that mesh with corresponding
teeth on the edge of disk 826. Driving gear 824 is powered by a
rotational energy applicator, such as a motor 822 or a manual
crank. A position sensor 828, preferably positioned over the
vicinity of the center of disk 826, monitors the motion of disk
828, so as to facilitate controlled ablation of stratum corneum by
the handheld device. In a preferred embodiment, position sensor 828
comprises an optical sensor, which detects motion of an optical
disk 830, preferably positioned in the center of disk 826. For
example, optical disk 830 may be marked with a pattern of radial
lines that are detected by the optical sensor. Alternatively,
position sensor 828 comprises a dedicated brush that passes over
dedicated position-indicating pads (not shown) on electrode board
818.
[0240] A plurality of driving electrodes 832 are arranged in one or
more radial lines 833 (only one such line is shown in FIG. 5 for
clarity of illustration), and electrically coupled to a control
unit (not shown). Using input from position sensor 828, the control
unit typically precisely controls the timing of activating driving
electrodes 832 in order to increase the likelihood that each
driving electrode is in good electrical contact with its target
contact pad at the instant of activation and for the duration of
current application. The control unit typically attempts to
activate a driving electrode when the driving electrode is in
contact with the middle of a contact pad. If this precise location
is not achieved, e.g., because of manufacturing or operation
variances, the driving electrode still typically makes good
electrical contact with a region of the contact pad other than its
middle.
[0241] Reference is now made to FIGS. 6A and 6B. FIG. 6A is a
schematic illustration of a printed circuit board (PCB) 40 for use
with the handheld devices shown in FIGS. 1, 2A, 3A, and 4A, in
accordance with a preferred embodiment of the present invention.
FIG. 6B is a schematic, sectional side-view of a portion of PCB 40,
in accordance with a preferred embodiment of the present invention.
PCB 40 is generally similar to electrode board 30, described
hereinabove with reference to FIGS. 2A and 4A, and contact board
230, described hereinabove with reference to FIG. 3A. Thus, the
lower surface of PCB 40 comprises either contacts or electrodes, as
appropriate. Except for differences described hereinbelow, PCB 40
is preferably configured to operate generally in accordance with
some or all of the techniques described herein for ablating stratum
corneum.
[0242] PCB 40 comprises a plurality of layers 42, 44 and 46.
Although only three layers are shown in FIG. 6 for clarity of
illustration, PCB 40 typically comprises a greater number of
layers, e.g., about four to eight layers. The upper surface of PCB
comprises a plurality of contact pads 33, which are similar to
contact pads 32, described hereinabove with reference to FIGS. 2A
and 4A, and contact pads 232, described hereinabove with reference
to FIG. 3A.
[0243] As is best seen in FIG. 6B, each contact pad 33 is
electrically coupled to at least one conductor 35, over one or more
traces 48, as is known in the art of PCB design and fabrication.
Conductor 35 comprises either a contact, as described hereinabove
with reference to FIGS. 2A and 4A, or an ablation electrode, as
described hereinabove with reference to FIG. 3A. The use of a PCB,
particularly a multi-layered PCB, allows conductors 35 to be
readily placed at locations other than in the vicinity of the
respective contact pads to which they are electrically coupled,
using PCB design techniques known in the art.
[0244] Reference is now made to FIGS. 7A and 7B. FIG. 7A is a
schematic sectional illustration of a PCB assembly 70, for optional
use with the handheld devices described hereinabove with reference
to FIGS. 1, 2A, 3A, and 4A, in accordance with a preferred
embodiment of the present invention. FIG. 7B is a schematic
illustration of a circuit representing PCB assembly 70, in
accordance with a preferred embodiment of the present invention.
PCB assembly 70 is generally used in a similar manner to PCB 40, as
described hereinabove with reference to FIGS. 6A and 6B. PCB
assembly 70 comprises at least two non-conducting layers, an upper
non-conducting layer 84 and a lower non-conducting layer 80. Upper
non-conducting layer 84 and lower non-conducting layer 80 are
separated by a conducting layer 82. Upper non-conducting layer 84
has coupled thereto a plurality of contact pads 72, which are
exposed on the top surface of the upper non-conducting layer. The
contact pads are electrically coupled to ablation electrodes 74 by
leads 88, which travel through channels 86, such as vias, shown in
FIG. 7A as vertical holes demarcated by dashed lines. Channels 86
thus electrically isolate leads 88 from conductive layer 82.
Additionally, each lead 88 is electrically coupled to the bottom
surface of lower layer 80 in the vicinity of the respective
electrode 75.
[0245] It is to be understood that PCB assembly 70 has been
described herein and shown in FIG. 7A with only two non-conducting
layers for simplicity of illustration only; generally PCB 70
comprises more than two non-conducting layers, as described
hereinabove with reference to FIGS. 6A and 6B. In addition,
although channels 86 are shown as simple vertical channels, they
may follow a more complex route through the layers of the PCB. In
addition, although PCB assembly 70 is described and shown as
comprising ablation electrodes 74, this is for the sake of
illustration only; PCB assembly 70 can also comprise contact board
contacts, as described hereinabove with reference to FIG. 3A.
[0246] Conducting layer 82 serves as a ground, and as such is
electrically coupled to a ground terminal of power unit 102. Lower
non-conducting layer 80 and/or upper non-conducting layer 84
naturally form the dielectric of a capacitive element 91, in which
conducting layer 82 is separated from electrodes 74 (and/or skin
150, contact pads 72, or conductors in electrical contact with
electrodes 74). Therefore, handheld devices that comprise PCB
assembly 70 in this configuration do not necessarily comprise a
return electrode that is specifically designated to function as a
ground. Instead, all of electrodes 75 are preferably given a small
capacitance to ground, by virtue of one or more of the
following:
[0247] (a) electrical coupling of the electrodes to lower-layer
contacts 89, in the vicinity of each respective electrode, and the
resultant capacitive coupling between lower-layer contacts 89 and
conductive layer 82,
[0248] (b) capacitive coupling between skin 150, in the region of
electrodes 74, and conductive layer 82, and
[0249] (c) capacitive coupling between contact pads 72 (which are
electrically coupled to electrodes 74) and conductive layer 82.
[0250] For some applications, PCB assembly 70 comprises a plurality
of conducting layers 82, separated from each other by respective
non-conducting layers (configuration not shown). Each
non-conducting layer comprises a plurality of contacts 89 typically
integrated within the non-conducting layer, with each of the
contacts directly electrically coupled to a respective pad 72.
Typically, each pad 72 is directly electrically coupled to a
plurality of contacts 89 located within respective non-conducting
layers. Such a configuration generally linearly multiplies the
total amount of capacitance. In one particular configuration, PCB
assembly 70 comprises four conducting layers 82, and each pad 72 is
coupled to four contacts 89, located within respective
non-conducting layers. For these applications, contacts 89
generally have a characteristic of about 0.5-4 mm2, and are
separated from the nearest conducting layer 82 by about 0.1-0.3
mm.
[0251] Since only a small fraction of the ablation electrodes are
energized at any one time, the remaining electrodes function as
return paths through capacitive element 91 to ground. Preferred
values for the capacitance provided by each of the electrodes
preferably corresponds to an impedance of, for example, 500
kilo-ohm to 2 mega-ohm for each electrode at the operating
frequencies. In this manner, the overall impedance is typically in
the range of about 0.5 kilo-ohm to 2 kilo-ohm if 1000 ablation
electrodes 74 are used.
[0252] Typically, the capacitance to ground provided by any one of
the electrodes is not so high as to constitute a short circuit in
the frequencies of the current application, when that electrode is
in contact with a driving electrode, because the impedance to
ground through that electrode is typically greater than 500
kilo-ohm.
[0253] Alternatively, capacitive element 91 comprises discrete
capacitors and/or resistors, coupled to each of the ablation
electrodes and to conducting layer 82 (configuration not
shown).
[0254] When a brush electrode 76 is brought into electrical contact
with a contact pad 73, current is driven to electrode 75. Most of
this current is delivered to skin 150, but a relatively small
portion of the current leaks capacitively to ground through
capacitive element 91 in the vicinity of electrode 75. A
substantial portion of the current (typically, at least 80%)
travels through skin 150 and returns to ground through the other
electrodes 74.
[0255] Reference is now made to FIGS. 8A and 8B, which are
schematic illustrations of an electrode set 160, in accordance with
a preferred embodiment of the present invention. FIG. 8A shows a
perspective side-view of electrode set 160, and FIG. 8B shows a
bottom-view of the electrode set. Electrode set 160 is preferably
used with handheld device 21 (described with reference to FIG. 3A),
or with the handheld devices described hereinabove with reference
to FIGS. 1, 2A, and 4A. Each electrode set preferably comprises at
least two wires, for example two wires, wire 180 and a wire 182,
which are bent (e.g., in the shape of a parabola, as shown, or in
the shape of a conventional staple, not shown) and crossed with one
another at an intersection point 172 (which is about at the middle
of each wire), such that the four ends of the two wires
substantially form a plane, and define ablation electrodes 178. For
some applications, electrode set 160 comprises three or more wires
(not shown). The wires are preferably formed by extrusion.
Preferably, cone- or pyramid-style pieces 174 (or pieces having
other shapes) surround and support electrodes wires 180 and 182,
such that the electrode portions of the wires protrude from the
cones or pyramids. Typically, wires 180 and 182 are not
mechanically secured to one another, but rather are held in
electrical contact with each other by virtue of the natural
mechanical properties of the wires when supported by pieces 174.
Alternatively, the wires are mechanically coupled to one another at
intersection point 172. Preferably, the diameter of the wires is
between about 40 and 200 microns.
[0256] FIGS. 8C and 8D are schematic illustrations of an alternate
embodiment of electrode set 160, in accordance with a preferred
embodiment of the present invention. In this embodiment, wires 180
and 182 are bent (e.g., in the shape of a conventional staple, as
shown, or in the shape of a parabola, not shown), but are not
crossed, unlike the embodiment described hereinabove with reference
to FIGS. 8A and 8B. Instead, a connecting portion 190 of a coupling
member 183 is placed on each of the wires, at points 179 and 181,
electrically coupling the wires together. (Coupling member 183 is
described hereinbelow with reference to FIG. 10.) As in the
embodiment shown in FIG. 8A, the four ends of the two wires
substantially form a plane, and define ablation electrodes 178.
Coupling member 183 passes through a hole 192 defined by electrode
cartridge 250.
[0257] FIG. 9 is a schematic sectional side-view illustration of a
portion of electrode set 160 in electrical contact with a contact
board contact 239, in accordance with a preferred embodiment of the
present invention. This embodiment is typically employed with the
embodiment of electrode set 160 illustrated in FIGS. 8A and 8B.
Pieces 174 are attached to or incorporated into the lower surface
of electrode cartridge 250 (FIG. 3C). When the upper surface of
electrode cartridge 250 (FIG. 3A) is brought in contact with the
lower surface of contact board 230 (FIG. 3B), as described
hereinabove with reference to FIGS. 3A, 3B and 3C, wire 180 makes
electrical contact with contact board contact 239 in the vicinity
of point 172. The pressure applied between electrode cartridge 250
and contact board 230 cause wire 180 to flex slightly, generally
resulting in good electrical contact between wire 180 and contact
board contact 239. Preferably, the pressure required to make good
electrical contact between each electrode set and the corresponding
contact board contact is relatively low, typically between about
0.5 and 4 grams. As a result, a typical user of the handheld device
is reasonably able to apply the total pressure (equal to the sum of
the pressure applied to each individual electrode set) necessary to
couple the electrode cartridge to the contact board. For example,
in embodiments of the device comprising 200 electrode sets, the
total pressure that would be applied could be 200 grams.
[0258] Preferably, the portion of wire 180 that protrudes from the
upper surface of electrode cartridge 250 has an unflexed height
L.sub.1 (i.e., a height prior to compression by contact board
contact 239) of between about 0.1 and 1 millimeter, and a flexed
height L.sub.1 of between 0 and 0.5 millimeters. The pieces
preferably have a height L.sub.2 of between about 0.1 and 1
millimeters. Preferably, the portion of wires 180 and 182 that
protrudes from cone-style pieces 174, and comprises electrodes 178,
has a length L.sub.3 of between about 0.02 and 0.20 millimeters.
Electrodes 178 of wire 180 are preferably spaced a distance L.sub.4
of between about 0.7 and 1.0 millimeters from each other.
Preferably, electrode sets 160 are spaced with a density of between
about 50 and 200 electrodes per square centimeter.
[0259] FIG. 10 is a schematic sectional illustration of coupling
member 183 electrically coupling the electrode set of FIGS. 8A and
8B or FIGS. 8C and 8D to a contact board contact 239, in accordance
with a preferred embodiment of the present invention. In the case
of the electrode set of FIGS. 8A and 8B, one end of coupling member
183 is in contact with wire 180 at intersection point 172. (Wire
180 in turn is in contact with wire 182, also at intersection point
172.) In the case of the electrode set of FIGS. 8C and 8D, this end
of coupling member 183 is in contact with both wires 180 and 182 at
connecting portion 190, as best seen in FIG. 8C. The other end of
coupling member 183, which is preferably hooked or otherwise shaped
to increase its contact surface area, makes electrical contact with
contact board contact 239 when the upper surface of electrode
cartridge 250 (FIG. 3A) is brought in contact with the lower
surface of contact board 230 (FIG. 3B), as described hereinabove
with reference to FIGS. 3A, 3B and 3C. The length L.sub.5 of
coupling member 183 is preferably between about 5.0 and 12.0
millimeters. The diameter of coupling member 183 is preferably
between about 20 and 60 microns.
[0260] FIG. 11 is a schematic sectional illustration of one of
electrodes 178, in accordance with a preferred embodiment of the
present invention. Wire 180, as it passes through cone- or
pyramid-style piece 174 in this embodiment, comprises an angular
bend 185, such as a crimp. Angular bend 185 typically serves to
maintain a constant length L.sub.3 of electrode 178, despite upward
and/or downward pressure that may be applied to electrode 178
during use. Use of an angular bend 185 is particularly useful in
supplementing the reduced friction force when wire 180 has a
diameter less than about 100 microns, and, even more so when the
diameter is less than about 60 microns.
[0261] FIG. 12 is a schematic illustration of a method for
sequencing the activation of electrodes 302, in accordance with a
preferred embodiment of the present invention. Electrodes 302,
distributed over an area 300, are activated in an activation
sequence pursuant to which the distances between each activated
electrode and the successively-activated electrode are generally
greater than such distances would be pursuant to a random
activation sequence.
[0262] For example, the group of six electrodes 302 shown in FIG.
12 is activated in the sequence indicated by the numbers with which
each electrode is labeled. For some applications, the activation
sequence is selected from a set of potential activation sequences
by calculating, for each potential activation sequence, the sum of
the distances between successively-activated electrodes, and
selecting the potential activation sequence that has the greatest
sum. Larger distances between successively-activated electrodes
generally minimizes any sensation of pain or discomfort that a
subject might experience during ablation.
[0263] The sequence is preferably configured to attempt to maximize
both the average distance between activated electrodes and the
minimum distance between activated electrodes. Should maximizing
the average distance and maximizing the minimum distance come in
conflict, then maximizing the minimum distance between activated
electrodes typically takes higher priority.
[0264] FIG. 13 is a schematic illustration of a method for
generating an activation sequence, as described with reference to
FIG. 12, in accordance with a preferred embodiment of the present
invention. According to this method, area 300 is divided into
rectangular regions 310, such as square regions, arranged in a
grid. During ablation, the device cycles through the regions 310,
so that successively-activated regions are in most instances at
least a minimum threshold distance apart, and activates an
electrode 302 in each region. The sequence is typically cycled
through at least twice, with a different electrode in each region
preferably activated each time the sequence is repeated. Since
sequential regions are generally at least the minimum threshold
distance apart, each electrode within a region is at least the
minimum threshold distance apart from the electrode activated in
the next region in the sequence. Therefore, the sequence of
activating electrodes within a given region during successive
cycles of the sequence is generally not important, which affords
flexibility in designing a contact board.
[0265] In a preferred embodiment, sequential regions are separated
by at least one intervening region, or are at least the distance of
a "knight's jump" (as in a game of chess) from one another, i.e.,
at least one column or row in a first direction, and at least two
columns or rows in a second direction perpendicular to the first
direction. In other words, sequential regions are not adjacent to
one another, including not diagonally adjacent. For example, an
electrode in region 1 (column D, row 1) is activated first. Next,
an electrode in region 2 (column C, row 3), which is one column and
two rows removed from region 1, is activated. Similarly, region 3
(column A, row 2) is a knight's jump from region 2. Note that
region 8 (column C, row 2) is more than a knight's jump from region
7 (column A, row 4), which relative location satisfies the general
minimum distance requirements of this sequencing method. After an
electrode has been activated in all sixteen regions of this
example, the sequence is repeated beginning with region 1, which is
also labeled region 17 to illustrate this repetition. It is to be
noted that this activation strategy is exemplary, and other
strategies will be readily apparent to those skilled in the art,
having read the present patent application. The sequence is
preferably configured to attempt to maximize both the average
distance between activated electrodes and the minimum distance
between activated electrodes.
[0266] Preferably, after a desired activation sequence of
electrodes is determined (optionally using the method described
with reference to FIG. 13), in order to implement the sequence
using the handheld devices described herein, one of the following
techniques, or, most preferably, both in combination, are used.
Techniques for achieving a desired activation sequence using other
skin ablation devices will be evident to those skilled in the art,
having read the present patent application. [0267] The handheld
device comprises power tracks 902, as described hereinabove with
reference to FIG. 4A. Power is supplied to only one power track 902
at a time. A power track generally provides power to only one power
transfer element at a time, because only one power transfer element
is typically in contact with a given power track at any time.
Activating different power tracks in sequence drives current into
the skin through a number of power transfer elements in sequence,
allowing for the rapid selection of ablation sites in different
sections of the ablation area, thereby achieving a distributed
activation sequence. [0268] The handheld device comprises a
multi-layered PCB, such as that described hereinabove with
reference to FIGS. 6A and 6B. Design of the PCB allows electrodes
to be readily placed at locations other than in the vicinity of
their corresponding contact pads. These locations are selected in
order to achieve a distributed activation sequence.
[0269] FIG. 14 is a flow chart that schematically illustrates a
method for calibrating a voltage, in accordance with a preferred
embodiment of the present invention. When forming micro-channels in
the stratum corneum, it is generally desirable to apply the minimum
energy necessary to successfully form the micro-channels.
Minimizing the applied energy reduces device energy requirements,
which is particularly beneficial for battery-operated devices.
Applying less energy may also reduce any sensation a subject might
feel during ablation. While an appropriate voltage to apply can be
pre-configured for an ablation device, it is desirable in some
applications to calibrate the applied voltage at least once per use
of the device. Such repeated calibration is beneficial because the
impedance of stratum corneum varies from subject to subject, and
even from time to time within a given subject (for example, because
of varying moisture levels of the stratum corneum). Furthermore,
for some applications, it is desirable to separately calibrate the
applied voltage for each of one or more ablation electrodes in an
array of electrodes, because the impedance of stratum corneum
sometimes varies even over a small area of skin.
[0270] In a preferred embodiment, this calibration is performed
using a technique of "feed-forward," as follows. A set of ablation
electrodes is applied to the skin of the subject, at an electrode
application step 200. Using at least one ablation electrode, a
brief calibration burst of energy in applied to the stratum
corneum, at a non-ablating burst application step 202. (One or more
appropriate return electrodes or other return contact surfaces are
used.) The calibration burst is applied at a relatively low energy
level, such that ablation substantially does not occur, or occurs
to a small extent compared to subsequently-applied ablation, and no
sensation is typically felt by the subject. For some applications,
the calibration burst is applied as a low current, a low voltage,
or even a relatively-high voltage applied for a short duration
(e.g., less than 500 microseconds or even less than 200
microseconds). The calibration burst is preferably applied by
applying a voltage drop between the at least one ablation electrode
and the return electrodes, typically, but not necessarily, a peak
voltage drop of between about 50 and 100 volts. Alternatively, the
calibration burst is applied using a known current, in which case a
peak current of between about 0.1 and 0.5 mA is typically applied.
A parameter of the calibration burst is measured, at a parameter
burst measurement step 204, which preferably is performed
simultaneously with step 202 (step 204 is shown in FIG. 14
subsequent to step 202 for clarity of illustration only). When the
calibration burst is applied by applying a voltage drop, the
parameter preferably is an amperage of a current generated as a
result of the application of the voltage drop. On the other hand,
when the calibration burst is applied by applying a current, the
parameter preferably is a measure of a voltage drop. The parameter
is generally indicative of a level of impedance in the
electrode/skin contact area of the stratum corneum, combined with
impedance of the electrodes and associated apparatus. Responsive to
the measured parameter, an appropriate energy level, such as a
voltage or an amperage, to use for subsequent ablation is
determined, at an energy level determination step 206. Using this
energy level, ablation is performed, at an ablation step 208.
[0271] In a preferred embodiment, steps 202 through 208 are
repeated in real-time for each of a plurality of ablation
electrodes of the array, each time ablation is applied. Applying
the calibration burst and measuring the parameter (steps 202 and
204) are preferably performed in less than about 1 millisecond, and
ablation is preferably applied (step 208) for less than about 4
milliseconds, most preferably for less than about 1 millisecond.
Typically, any given contact pad is electrically coupled to the
control unit for about 1 to 25 milliseconds.
[0272] Alternatively, steps 202 through 208 are performed only
once, at the commencement of an ablation procedure, using a single
ablation electrode or a plurality of electrodes. A single
calibrated energy level is determined, and this energy level is
preferably used for all of the ablation electrodes activated during
the ablation procedure. Because the natural impedance of stratum
corneum prior to ablation is relatively high, using a plurality of
electrodes typically results in a more accurate measurement of
impedance because total current is greater than if only a single
ablation electrode were to apply a single sub-ablation calibration
voltage. For some applications, this energy level calibration
procedure is combined with an impedance-sensing procedure performed
in order to determine initial contact of the electrode array with
the skin of the subject.
[0273] FIG. 15 is a schematic sectional illustration of a
pressure-sensing mechanism 400 for use with the devices described
with reference to FIGS. 1, 2A, 3A, and 4A, in accordance with a
preferred embodiment of the present invention. For simplicity of
description, pressure-sensing mechanism 400 is described herein
with reference to handheld device 21, described hereinabove with
reference to FIGS. 3A, 3B and 3C, although the pressure-sensing
mechanism applies equally well to the devices described with
reference to FIGS. 1, 2A and 4A. Pressure-sensing mechanism 400 is
used to provide an indication that firm contact has been made
between electrode cartridge 250 and skin 150 of the subject,
responsive to which indication an ablation procedure is begun.
[0274] Pressure-sensing mechanism 400 comprises a floating element
402, coupled to handle 229 by a pivot joint 404, which allows the
floating element to pivot in the rotational directions indicated by
arrow 414. Contact board 230 is fixed to the lower surface of
floating element 402. Electrode cartridge 250 is removably coupled
to contact board 230 using clips, such as snaps 412. The snaps are
adapted to prevent the electrode cartridge from separating from
contact board 230 (as would otherwise typically occur because of
the force of gravity), while generally not applying any upward
pressure on the electrode cartridge
[0275] A spring 410 applies downward pressure on floating element
402. As a result, when the electrode cartridge is not in firm
contact with the skin, floating element 402 pivots (shown as
clockwise pivoting in FIG. 15) until the end of the floating
element furthest from pivot joint 404 comes in contact with and is
prevented from further pivoting by a stop element 416 fixed to
handle 229. When electrode cartridge 250 is brought in contact with
skin 150, and downward pressure is applied by the electrodes
against skin 150, floating element 402 is pushed upward, activating
a switch 406 on the floating element or elsewhere on the apparatus
provided in this embodiment. As a result, a signal is generated
indicating that firm contact has been made between electrode
cartridge 250 and skin 150. Typically, switch 406 comprises a
simple on-off switch or a general-purpose force transducer.
[0276] FIG. 16 is a schematic sectional illustration of packaging
420 for storing an electrode-containing element 422, in accordance
with a preferred embodiment of the present invention. For
simplicity of description, packaging 420 is described herein with
reference to handheld device 100, described hereinabove with
reference to FIG. 1, although packaging 420 can be used equally
well in conjunction with the devices described hereinabove with
reference to FIGS. 2A, 3A and 4A.
[0277] Packaging 420 comprises a container 426, preferably
comprising blister packaging. Container 426 is shaped so as to
define a first indentation 428, adapted to store a single
electrode-containing element 422, such as an electrode cartridge
250, described hereinabove with reference to FIGS. 3A, 3B and 3C,
or an electrode board 30, described hereinabove with reference to
FIGS. 2A, 2B and 4A. Indentation 428 has a shape similar to
electrode-containing element 422, such that the element sits
securely in the indentation. Electrode-containing element 422
protrudes from indentation 428 by a distance of L, which is a
sufficient distance to allow the element to couple to the handle.
For example, L may be between about 1 and about 5 mm. To close the
packaging, container 426 is covered with a removable covering 424.
A second indentation 431 accepts the handle, thereby guiding the
handle to accurately and firmly couple with electrode-containing
element 422. Second indentation 431 is positioned so that the plane
formed by the electrodes of electrode-containing element 422 and
the plane formed by covering 424 form an angle alpha, the angle
typically between 5 and 90 degrees, preferably between about 10 and
35 degrees. The angle is preferably configured to facilitate easy
grasping of the handle by a user during removal of
electrode-containing element 422 from packaging 420, given that
electrode-containing element 422 does not protrude from packaging
420.
[0278] In order to attach electrode-containing element 422 to
handle 130 (or contact board 230, as the case may be), covering 424
is removed by the user. Handle 130 is inserted into an open area
430 of packaging 420 and positioned substantially at angle alpha to
the plane formed by covering 424 prior to its removal. The handle
is then brought in contact with the top of electrode-containing
element 422, and pressure is applied, which couples the handle to
the electrode-containing element. The handle is then removed from
the packaging.
[0279] FIGS. 17A and 17B are schematic illustrations of apparatus
600 for enabling transdermal transport of a substance, such as a
drug, in accordance with a preferred embodiment of the present
invention. Except for differences described hereinbelow, apparatus
600 is preferably configured to operate generally in accordance
with techniques described herein for ablating stratum corneum.
[0280] Preferably, a handheld unit including at least one
high-voltage driving electrode 650, a return electrode 652, and a
power source (not shown) is passed by the user over an electrode
cartridge 602, which typically comprises a set of monopolar
receiving electrodes 610 and a return strip 614. Electrodes 610 and
return strip 614 preferably pass through electrode cartridge 602
from the top surface thereof (FIG. 17A) to the bottom surface
thereof (FIG. 17B), so as to contact skin 150 when the electrode
cartridge is placed on the skin. Alternatively, the electrodes are
configured by other means to electrically connect the top and
bottom surfaces of electrode cartridge 602. In this manner, as the
handheld unit is passed over the electrode cartridge, driving
electrode 650 preferably comes into contact with each of receiving
electrodes 610, and drives current through these electrodes into
skin 150. Simultaneously, return electrode 652 makes contact with
return strip 614 on electrode cartridge 602, allowing current
injected into skin 150 to return to the handheld unit. Preferably,
the current is configured so as to produce local ablation at the
contact sites of each of electrodes 610 with skin 150. There is
typically no substantial heating where return strip 614 contacts
the skin, because the strip preferably has a significantly larger
contact area than the total contact area of each of electrodes
610.
[0281] For some applications, the location of each of electrodes
610 on electrode cartridge 602 is arranged such that as the
handheld unit is passed over the electrode cartridge, driving
electrode 650 makes simultaneous contact with a desired number of
electrodes 612 before contacting a subsequent group of one or more
electrodes 613. Thus, as appropriate, electrodes 610 may be
arranged in: (a) a staggered grid (FIGS. 17A and 17B), (b) a
rectangular grid, with one or more electrodes in each dimension, or
(c) a line parallel to return strip 614, so as to allow only one
electrode to be contacted at a time. Alternatively or additionally,
other geometries are used so as to provide contact, at any given
time, between one or more of electrodes 610 and driving electrode
650.
[0282] Preferably, the shape of the surface of electrode cartridge
602 is configured in accordance with the desired motion of the
handheld unit. For example, return strip 614 may be recessed into
the surface of the electrode cartridge, in a manner which
facilitates desired contact between the handheld unit and the
electrode cartridge.
[0283] If appropriate, the power source may be configured to apply
the current such that two or more passes of the handheld unit over
the electrode cartridge produce the desired extent of ablation of
the stratum corneum. It is noted that although the handheld unit is
shown in FIGS. 17A and 17B as being configured for manual
operation, automated means may also be provided for moving driving
electrode 650 over each of electrodes 610 on electrode cartridge
602.
[0284] For some applications, a drug to be applied through the skin
is incorporated into apparatus 600, e.g., around electrodes 610.
Alternatively, the drug may be applied to the skin following
treatment of the skin and removal of electrode cartridge 602
therefrom, e.g., by means of a standard medicated patch placed on
the treated region.
[0285] FIG. 18 is a schematic illustration of a device 700 for
enabling transdermal transport of a substance, such as a drug, in
accordance with a preferred embodiment of the present invention.
Except for differences described hereinbelow, device 700 is
preferably configured to operate generally in accordance with
techniques described herein for ablating stratum corneum.
[0286] Device 700 functions in a similar manner to device 600 of
FIG. 17A, except that whereas device 600 typically comprises a
single driving electrode 650 (FIG. 17A), device 700 comprises at
least two driving electrodes 704 and 708. Although only two driving
electrodes are shown in FIG. 18, it is to be understood that a
greater number of driving electrodes, such as up to 10 or up to
100, are appropriate for many applications. The multiple driving
electrodes allow for more control over the activation of individual
electrodes that are in contact with the skin. Device 700
additionally comprises a return electrode 702, a power source (not
shown), and an electrode cartridge 706, which typically comprises
an electrode array 710 and a return strip 724.
[0287] In a preferred embodiment, electrode 708 is activated on a
first pass of device 700 over electrode cartridge 706, while
electrode 704 is activated on a subsequent pass of device 700 over
electrode cartridge 706. Partial activation of electrode array 710
reduces the instantaneous power requirement of device 700, which is
important for battery-powered devices, as batteries are limited in
the current and voltage they can deliver at any given moment.
[0288] Additionally, by stimulating only a limited number of
electrodes at any given time, the sensation felt by the patient can
be reduced. Reducing the sensation felt by a patient is achieved by
limiting the density of stimulated electrodes at any given instant.
Staggered electrode array 710 and multiple driving electrodes 704
and 708 have the effect of reducing the number and density of
simultaneously stimulated electrodes. For example, during a first
pass of device 700 over array 706, driving electrode 708 is
activated while driving electrode 704 is not activated. Thus,
ablation electrode 712 is activated first, followed by electrode
714, to be followed by electrode 720, et cetera, such that only one
electrode is activated at a time. Similarly, on the second pass,
driving electrode 704 is activated while electrode 708 is not
activated, resulting in the sequence of stimulated electrodes 716,
718, 722, et cetera. Typical electrode cartridges 706 have many
more electrodes than shown in FIG. 18, but the same principle is
preferably applied to reduce instantaneous power requirements and
the concentration of stimulated electrodes.
[0289] For some applications, electrode contacts on one side of
electrode cartridge 706 are coupled to electrodes on the other
side, in a configuration that generally maximizes the distance
between sequentially-activated electrodes (e.g., using techniques
described hereinabove with respect to traces and vias in a
multi-layer PCB, applied here to electrode cartridge 706). In this
case, only one pass is typically utilized.
[0290] FIG. 19 is a schematic illustration of a device 740 for
enabling transdermal transport of a substance, such as a drug, in
accordance with a preferred embodiment of the present invention.
Except for differences described hereinbelow, device 740 is
preferably configured to operate generally in accordance with
techniques described herein for ablating stratum corneum.
[0291] Device 740 functions in a similar manner to device 700 of
FIG. 18, but while device 700 is moved manually, device 740 is
automated. Device 740 comprises several mating holes 752, which fit
over corresponding mating pegs 766 on an electrode cartridge 760,
to ensure proper alignment of the two parts. Preferably, the top of
electrode cartridge 760 comprises a return strip 762 and an array
764 of electrode pads 768, which couple to conductors (not shown)
on the bottom of electrode cartridge 760. The conductors comprises
either contacts, as described hereinabove with reference to FIGS.
2A and 4A, or ablation electrodes, as described hereinabove with
reference to FIG. 3A. In the latter case, device 740 preferably
comprises an electrode cartridge similar to electrode cartridge
250, described hereinabove with reference to FIG. 3A, which
cartridge is removably coupled to the device. Device 740
additionally comprises a return electrode 742 and a power source
(not shown).
[0292] Pads 768 serve as connectors between a plurality of driving
electrodes 754 and the conductors. Driving electrodes 754 are
preferably coupled to a manifold 744, such that the terminal ends
of driving electrodes 754 come in contact with a diagonal line of
pads 768, for example diagonal line 769, which has the effect of
reducing the density of stimulated electrodes at any instant. This
reduces the sensation felt by the patient during treatment with
device 740, as described hereinabove. Alternatively, a staggered
pattern of pads 768 is contacted by driving electrodes 754 at a
given moment of time. Preferably, driving electrodes 754 comprise
brush electrodes, which make electrical contact with pads 768.
[0293] It will be appreciated that a variety of arrangements of
contact pads and driving electrodes may be utilized, and that the
particular configuration shown in FIG. 19 is by way of illustration
and not limitation. In addition, although for simplicity only
sixteen contact pads 768 are shown in the figure, a larger number
(e.g., 240) is preferably used, arranged in an array appropriate
for a particular application, such as 4.times.60, or 12.times.20.
In turn, each of the contact pads is preferably coupled to more
than one conductor on the lower surface of electrode cartridge 760.
In one preferred embodiment, each pad 768 is directly coupled to
four conductors.
[0294] Manifold 744 is preferably coupled to a driving mechanism
such as a belt 746, which is disposed around two cylinders 748. A
motor 750 is coupled to one of cylinders 748, so as to cause
movement of belt 746 and of driving electrodes 754. To effect the
desired movement of driving electrodes 754 over pads 768, a control
unit (not shown) is preferably used to activate and control motor
750. In a preferred embodiment, the control unit selectively
activates one or more of driving electrodes 754 during each pass of
the driving electrodes over pads 768, such that after one or more
passes substantially all of the conductors have been activated. As
described hereinabove, only one or a portion of the driving
electrodes are typically activated at any one time, so as to reduce
the instantaneous power requirements of the device and to minimize
sensation felt by the patient.
[0295] Preferably, methods and apparatus described in U.S. patent
application Ser. No. 09/859,645 to Avrahami and Sohn, entitled,
"Monopolar and bipolar current application for transdermal drug
delivery and analyte extraction," filed May 17, 2001, which is
assigned to the assignee of the present patent application and is
incorporated herein by reference, are utilized in combination with
the methods and apparatus described herein.
[0296] It is noted that the figures depicting preferred embodiments
of the present invention are not necessarily drawn to scale, and,
instead, change certain dimensions in order to more clearly
demonstrate some aspects of the invention.
[0297] It is further noted that whereas preferred embodiments of
the present invention are generally described herein with respect
to ablating the stratum corneum to facilitate substance delivery,
the scope of the present invention includes ablating the stratum
corneum so as to facilitate analyte extraction.
[0298] It will be appreciated by persons skilled in the art that
the present invention is not limited to what has been particularly
shown and described hereinabove. Rather, the scope of the present
invention includes both combinations and subcombinations of the
various features described hereinabove, as well as variations and
modifications thereof that are not in the prior art, which would
occur to persons skilled in the art upon reading the foregoing
description.
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