Steerable combined catheter with flush hub

Abstract

A catheter assembly comprising a guide catheter with a handle portion arranged inside a han- dle. The catheter has a tubular wall in which a pair of opposed wire lumens are arranged. The wire lumens terminate in a pair of opposed exit side openings arranged in the distal handle portion. The guide catheter comprises a pair of control wires exiting from the exit side openings. 5 The handle comprises a deflection control member attached to the control wire proximal end portions and adapted to exert an axial pull or push force to the control wires to thereby deflect the distal end of the guide catheter. A flush hub is attached to and seals the guide catheter proximal end, the flush hub comprising a proximal sealing valve from which the delivery cath- eter exits, the sealing valve allowing axial and rotational movement of the delivery catheter 10 relative to the flush hub and thus the guide catheter.

Description

[0001] 240047W001

[0002] 1

[0003] STEERABLE COMBINED CATHETER WITH FLUSH HUB

[0004] The present invention relates to catheter-based cell delivery systems and components therefor adapted for delivery of a cell formulation to a tissue site. In a specific embodiment the system is adapted for delivery of a cell formulation to a myocardial treatment site. Alternatively, the

[0005] 5 disclosed catheter system may be used for delivery of fluid drugs in general to a tissue site.

[0006] BACKGROUND OF THE INVENTION

[0007] In the disclosure of the present invention reference is mostly made to the treatment of the heart by ventricular delivery of a fluid substance, however, this is only an exemplary use of the pre¬

[0008] 10 sent invention.

[0009] The present invention generally relates to medical methods and systems suitable for trans- endocardial intramyocardial delivery of cellular material in the form of a fluid cell or cell aggregate substance to the heart via a peripheral artery for the treatment of e.g. acute myocardial infarction, chronic myocardial ischemia, ischemic heart failure, and nonischemic heart failure.

[0010] WO 00 / 9185 and US 2003 / 0195469 disclose different designs for a combined catheter comprising an outer steerable shaft from which a hollow helical delivery needle can be rotationally advanced, either relative to the outer shaft or by retracting a tubular sheet covering the helical needle. The hollow helical needle is supplied with torque and fluid via separate structures designed to provide and allow the relative movement between the helical needle and the outer shaft. Steering of the outer shaft is provided by a pair of opposed pull wires guided in tubular lumens in the outer shaft wall, the pull wires providing deflection in a plane of the distal-most part of the outer shaft in which the helical needle initially is located. A specific embodiment

[0011] 25 comprises a rotational knob allowing a user to control deflection of the inner delivery catheter via pull wires, as well as a fluid port for supplying fluid to the delivery catheter. No structures are described allowing the interior space of the outer shaft to be flushed.

[0012] WO 00 / 06242 discloses a catheter coupled to a handle and which is steerable via a handle control wheel coupled to axially extending pull wires. The steerable catheter comprises one or more axially extending lumens terminating in a handle terminal from which the pull wires as well as tubular extensions of the catheter lumens extend proximally. Each of the one or more tubular extensions terminates in an inlet structure allowing an instrument to be introduced into the tubular extension and subsequently into one of the catheter lumens. Each inlet structure

[0013] 35 may be provided with a flush port, however, from the narrow inner diameter of the inlet structure it appears that flushing is not intended with an instrument in place. 240047W001

[0014] 2

[0015] US 2024 / 0148504 discloses a catheter for delivering a medical implant, comprising a plurality of concentrically arranged tubes, the innermost tube providing a lumen adapted to axially receive a guide wire, whereas the outer tubes create several circumferential spaces there¬

[0016] 5 between. The catheter comprises a first port through which the guide wire lumen can be flushed before a guide wire is inserted therethrough, as well as a second combined flush port which via connector hubs allows the individual circumferential spaces to be flushed. The catheter is also provided with a pull wire extending to the distal end via one of the circumferential spaces.

[0017] 10

[0018] US 2002 / 0115983 discloses a steerable catheter with a tubular lumen adapted for guiding e.g. an endoscope into a hollow organ or body cavity to examine. A handle comprises a connector allowing an endoscope to be inserted there though and into the tubular lumen, as well as a fluid inlet port allowing a fluid to be introduced into the tubular lumen.

[0019] US 11 ,986,611 discloses a catheter with an axially deployable helical infusion needle. The catheter is optimized for radial artery introduction with a small outer diameter and is not steerable on its own for which reason is has to be advanced to its delivery location via a steerable guide sheath or a guide sheath in combination with a guide wire.

[0020] Having regard to the above, it is an object of the present invention to provide a combined catheter comprising a delivery catheter axially deployable from a steerable outer shaft in which access to the annular space between the outer shaft and the inner catheter can be controlled in a reliable, space-efficient and cost-effective way. In a specific aspect of the invention, it is

[0021] 25 an object to provide such a catheter assembly adapted for intramyocardial delivery of cells or cell agglomerates in a fluid suspension.

[0022] It is a further object of the invention to provide such a combined catheter in which the delivery catheter comprises a helical needle and in which axial advancement and rotational control of the helical needle can be provided by handle control means allowing for safe and effective operation.

[0023] It is a yet further object of the invention to provide a combined steerable delivery catheter comprising an inner delivery catheter with a distal helical infusion needle axially deployable

[0024] 35 from a steerable outer shaft having a small outer diameter. In a specific aspect of the invention, 240047W001

[0025] 3 it is an object to provide such a catheter assembly adapted for intramyocardial delivery of cells or cell agglomerates in a fluid suspension.

[0026] It is a yet further object of the invention to provide a suspension transfer system which safely

[0027] 5 and effectively can transfer a liquid suspension to a delivery catheter. It is a specific object to provide a cell suspension transfer system which safely and effectively can transfer a liquid cell suspension to a delivery catheter.

[0028] DISCLOSURE OF THE INVENTION

[0029] 10 In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.

[0030] Thus, in a first aspect of the invention a catheter assembly is provided, comprising a guide catheter, a delivery catheter, a handle and a flush hub. The guide catheter comprises a tubular wall defining a central lumen, a free portion with a distal end, and a proximal handle portion, a pair of opposed wire lumens arranged in the tubular wall, a pair of opposed exit side openings in communication with respective wire lumens and arranged in the proximal handle portion, and a pair of opposed control wires, each control wire having a main portion guided in a respective wire lumen, a distal end anchored distally in the tubular wall, and a proximal end portion exiting from the wire lumen via the exit side opening. The delivery catheter has a central lumen and comprises a main portion arranged axially and rotationally moveable in the guide catheter central lumen, and a proximal portion with a proximal fluid inlet. The handle in which the guide catheter proximal handle portion is arranged and from which the guide catheter free

[0031] 25 portion extends, comprises a housing, and control means attached to the control wire proximal end portions and adapted to exert an axial pull or push force to the control wires to thereby deflect the distal end of the guide catheter. The guide catheter has a proximal fluid inlet end arranged within the housing and from which the delivery catheter proximal portion exits, and the delivery catheter proximal portion exits from the housing. The flush hub is arranged in the housing and comprises a distal end attached to the guide catheter and sealingly surrounding the guide catheter proximal fluid inlet, a proximal sealing valve from which the delivery catheter proximal portion exits, the sealing valve allowing axial and rotational movement of the delivery catheter relative to the flush hub and thus the guide catheter, and a flush port in fluid communication with an interior of the flush hub, whereby the axially extending space between the

[0032] 35 delivery catheter and the guide catheter can be flushed with a fluid via the flush port. 240047W001

[0033] 4

[0034] By this arrangement, in which the pull wires exit side openings in the guide catheter arranged distally of the guide catheter proximal fluid inlet end, steering and flushing of a combined catheter assembly can be provided in a functional and space-efficient way.

[0035] 5 In an exemplary embodiment the control means comprises a control member arranged rotatable relative to the housing, the control wires being attached to the control member such that rotation of the control member relative to the housing causes a pulling respectively a pushing force to be applied to the pair of control wires.

[0036] 10 The catheter assembly may further comprise a tubular compression coil arranged in each of the wire lumens to axially surround and support the respective control wires along at least a portion of their length. Each compression coil may comprise a free proximal coil portion exiting from the corresponding wire lumen via the exit side opening, each proximal coil portion surrounding a portion of a control wire proximal end portion and being attached to the handle housing.

[0037] The guide catheter proximal fluid inlet end may be arranged in the housing proximally of the control means.

[0038] In an exemplary embodiment the guide catheter free portion comprises a main portion with the pair of opposed control wires, the central lumen having a first diameter, and a distal portion having a tubular wall forming a distal cavity with a second larger diameter. The delivery catheter comprises a distal hollow helical needle in fluid communication with the delivery catheter central lumen, the hollow helical needle having an outer diameter smaller than the second

[0039] 25 diameter but larger than the first diameter, the hollow helical needle comprising one or more outlet openings and being moveable from a retracted position arranged within the cavity to an extended position projecting from the cavity.

[0040] In a further exemplary embodiment, the handle comprises an actuator member and a clutch. The clutch is operatable between (a) an unlocked state in which the delivery catheter can be moved axially relative to the guide catheter, and (b) a locked state in which the delivery catheter cannot be moved axially relative to the guide catheter yet can be rotated relative to the guide catheter by rotation of the actuator member relative to the housing. By “axially locked” is to be understood a locked state in which the delivery catheter cannot be moved axially by the user

[0041] 35 by pulling or pushing. The clutch may be operatable between the unlocked state and the locked state by axial movement of the actuator member relative to the housing. 240047W001

[0042] 5

[0043] In a second aspect of the invention a catheter assembly is provided, comprising a guide catheter and a handle. The guide catheter comprises a tubular wall defining a central lumen, a distal free portion and a proximal handle portion, a pair of opposed wire lumens arranged in

[0044] 5 the tubular wall, a pair of opposed exit side openings in communication with respective wire lumens and arranged in the distal handle portion, and a pair of opposed control wires. Each control wire has a main portion guided in a respective wire lumen, a distal end anchored in the tubular wall distal end portion, and a proximal end portion exiting from the wire lumen via the exit side opening. The handle in which the guide catheter proximal handle portion is arranged

[0045] 10 and from which the guide catheter distal free portion extends, comprises a housing as well as control means attached to the control wire proximal end portions, the control means being adapted to exert an axial pull or push force to the control wires to thereby deflect the distal end of the guide catheter.

[0046] By this arrangement, a high degree of design freedom is provided for the proximal end of the guide catheter as the control wires exit the catheter distally of the proximal end, this in contrast to a traditional design in which the control wires exit at the proximal end of the guide catheter.

[0047] The catheter assembly provided in accordance with the second aspect of the invention may be provided with additional features as set out above for the catheter assembly in accordance with the first aspect of the invention.

[0048] A primary objective of the invention relates to catheter-based cell delivery systems and components therefor adapted for delivery of a cell formulation to a tissue site, however, the dis¬

[0049] 25 closed catheter system may alternatively be used for delivery of fluid drug. The term "drug" is meant to encompass any drug formulation capable of being passed through a delivery catheter and into the specified target site. The drug may be a single drug compound or a premixed or co-formulated multiple drug compounds drug agent from a single reservoir. Representative drugs include pharmaceuticals such as peptides, proteins, and hormones, biologically derived or active agents, hormonal and gene-based agents, nutritional formulas and other substances in both suspended and liquid form.

[0050] BRIEF DESCRIPTION OF THE DRAWINGS

[0051] In the following exemplary embodiments of the invention will be described with reference to

[0052] 35 the drawings, wherein: 240047W001

[0053] 6 fig. 1 shows a perspective view of a catheter assembly comprising a combined catheter and a handle, the combined catheter comprising an outer guide catheter and an inner delivery catheter, fig. 2 shows a perspective detail view of the distal-most portion of the catheter of fig. 1 ,

[0054] 5 fig. 3 shows an x-ray view of the guide catheter distal portion, fig. 4 shows a longitudinal cross-sectional view of the combined catheter distal end, fig. 5 shows a transversal cross-sectional view of the combined catheter, fig. 6 shows an exploded view of the handle, fig. 7 shows the handle seen from below with a lower housing portion removed,

[0055] 10 fig. 8 shows a longitudinal cross-sectional view of the handle as shown in fig. 7, fig. 9 shows the components of a dose delivery device, fig. 10 shows a longitudinal cross-sectional of the dose delivery device of fig. 9 in an assembled state, and fig. 11 shows an alternative configuration of a dose delivery device to be used in combination with a syringe.

[0056] In the figures like structures are mainly identified by like reference numerals.

[0057] DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0058] When in the following terms such as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical” or similar relative expressions are used, these only refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. When the term member or element is used for

[0059] 25 a given component, it generally indicates that in the described embodiment the component is a unitary component, however, the same member or element may alternatively comprise a number of sub-components just as two or more of the described components could be provided as unitary components, e.g. manufactured as a single injection moulded part. The terms “assembly” and “subassembly” do not imply that the described components necessarily can be assembled to provide a unitary or functional assembly or subassembly during a given assembly procedure but is merely used to describe components grouped together as being functionally more closely related.

[0060] With reference to figs. 1-8 an exemplary embodiment of a catheter-based cell delivery system

[0061] 35 will be described, the system comprising a catheter assembly 1 comprising a steerable tubular guide catheter and a therein arranged fluid delivery catheter, as well as a dose control device 240047W001

[0062] 7 adapted to supply a cell suspension to the fluid delivery catheter. For illustrative purposes, in the figures the catheters are shown having a reduced length. In an exemplary actual embodiment, the free length of the guide catheter is approximately 110 cm and the full length of the delivery catheter from the distal tip to the proximal injection port is approximately 150 cm.

[0063] 5

[0064] As shown in fig. 1 the assembly comprises a main or outer shaft 10 in the form of a steerable tubular guide catheter attached to a handle 100, and an inner shaft 20 in the form of a fluid delivery catheter arranged rotationally and axially moveable within the guide catheter and extending through the handle, the delivery catheter comprising a distal helical delivery needle 30.

[0065] 10 The handle comprises a deflection control member 200 for controlling deflection of the distal end of the guide catheter, a combined control member 300 for controlling axial and rotational movement of the fluid delivery catheter relative to the guide catheter, a proximal injection port 400 in fluid communication with the fluid delivery catheter, a flush port 500 in fluid communication with the tubular space between the guide and delivery catheter, and a wire connector 600 communicating with the helical needle 30.

[0066] Fig. 2 shows a detail view of the distal end 13 of the guide catheter 10 with the helical needle 30 mounted on the delivery catheter 20 extending therefrom. As will be described in greater detail below, the helical needle can be moved axially between a retracted position in which the helical needle is housed inside the guide catheter distal end, and an extended position as shown.

[0067] The hollow helical needle 30 is in an exemplary embodiment manufactured from stainless steel 304 (SS304) and comprises an atraumatic distal tip 31 and one or more exit openings 32 in

[0068] 25 the distal part for delivery of a fluid suspension to a treatment site. In an exemplary embodiment the helical needle is formed from tubing with a 0.25 mm ID and a 0.50 mm OD (25G), the helix having a 1 .6 mm OD and comprising three coils with a 1 mm pitch and a proximal centred stem portion 35 attached in fluid communication to the distal end of the delivery catheter, e.g. by welding.

[0069] Referring to figs. 3-6 the guide catheter 10 comprises a dual deflection main portion adapted to navigate through vasculature and carry the needle housed in the distal tip portion 13 to the desired location.

[0070] 35 The main portion has a tubular wall 11 forming a central lumen 12 through which the delivery catheter 20 extends thereby forming an axially extending circular space 12A. Along most of its 240047W001

[0071] 8 length the tubular wall comprises an embedded helical braiding formed from stainless steel threads. The braiding may vary along the length of the guide catheter (e.g. material, dimensions, and pitch) to provide the desired amount of pushability, flexibility and torqueability. The wall may be made from reflowing Pebax ® (a block copolymer variation of PEBA) of different

[0072] 5 stiffness over the braid and an inner liner, e.g. made from polyimide (PI). The tubular wall comprises a pair of opposed tubular lumens 15 in which a pair of corresponding compression coils 16 are embedded, the coils terminating at a distance from an embedded distal pull ring 19. Extending through the compression coils a pair of axially moveable control wires 17 are arranged, the control wires being connected to the deflection control member 200 at their prox¬

[0073] 10 imal ends and to the pull ring 19 at their distal ends, this allowing the distal end of the guide catheter to be deflected in a plane. The compression coils reduce the guide catheter’s tendency to buckle when the control wires are actuated. In an exemplary embodiment the diameter of the control wire is 0.20 mm, the inner diameter of the compression coil is 0.23 mm, and the outer diameter of the compression coil is 0.38 mm. Although the control wires may transfer a pulling force as well as a pushing force, they are traditionally termed pull wires which term will be used in the below description of the exemplary embodiment.

[0074] In the following an exemplary way of manufacturing the guide catheter will be described. As a first step a Teflon line is stretched over the length of an inner lumen mandrel. All second lumens are then position over the main lumen Teflon liner. At this point, the second lumens are a combination of their desired material composition (Teflon or Polyimide) and small mandrels to control their shape and position. At this point, the assembly of components is being “locked in” by assembling the braid made from SS304. This is performed in equipment referred as a braider that braids a number of specified stainless-steel wires in an orderly manner, respecting

[0075] 25 the pitch of the different sections of the shaft. This is typically programmed into the equipment, so it is the same every time. Once braiding is completed, the PEBAX extrusion segments are fed on the braided assembly as specified by the design. Harder durometer is used to give the shaft stiffness and torqueability and softer durometer is used to create the deflection segments. Once all the extrusions are positioned, a long PET heat-shrink if positioned over the assembly. Once in place, both ends of the PET are shrinked in place using a heat gun to “lock” everything in place. The assembly is now ready to be reflowed using proprietary equipment. This equipment is normally a motorized hot air machine that very slowly run a circular die feeding hot air on along the length of the assembly. This can be performed horizontally or vertically but vertically better ensures that the shaft remains axially symmetrical. The hot air essentially melts

[0076] 35 the PEBAX briefly allowing it to both bite in the braid and ensure smooth transition between the different durometer extrusions. Once cooled the PET is cut out and the shaft is revealed. 240047W001

[0077] 9

[0078] For a complex design, this last step is repeated a couple of times in phases to allow assembly of the pull wires and the compression coils which require the second lumens mandrel to be removed if present. At this point there is normally some finishing work performed on the PEBAX to ensure that there are no sharp edges on the ends, that the shaft, pull wires and compression

[0079] 5 coils are cut to length, etc. The main lumen mandrel is then pulled out and the assembled shaft is completed. The shaft is then annealed to ensure that it will maintain its shape and dimensions during aging as polymer may shrink with time and braid may relax during the same period so annealing reduces this phenomenon before the shaft can be used as part of the assembly.

[0080] 10 The tubular distal tip portion 13 has the same OD as the main portion but a lumen with a larger ID, the lumen forming a cavity 14 for housing the helical needle during advancement of the combined catheter. The distal tip portion is relatively soft and flexible comprising no braiding and being manufactured from a softer material than the neighbouring portion of the catheter. The tip portion comprises a distal embedded marker band 13A allowing the distal tip to be observed by e.g. X-ray during operation.

[0081] The proximal main portion of the delivery catheter to which the helical needle is attached comprises as the core component a stainless-steel tube 22 with a plurality of laser cut transversal slots along its length, the specific cut pattern providing the desired balance of flexibility, pushability and torque transmission. The laser cut tube (LCT) is embedded in inner and outer layers 23, 24 of e.g. Pebax ® 35D. The inner fluid transmission lumen 21 is provided with an inner liner 25 of e.g. PI. In fig. 4 the delivery catheter is shown without the helical needle.

[0082] Turning to fig. 6 an exploded view of the handle 100 is shown without the guide catheter and

[0083] 25 the delivery catheter. The handle comprises an upper housing part 110 with a cylindrical proximal bore portion 111 having an inner thread 112 (see fig. 8), and a lower housing portion 120. In the housing three main subassemblies are housed: In the distal portion a deflection control assembly for the guide catheter is arranged, in the middle portion a flush assembly is arranged, and at the proximal end a combined control assembly for the delivery catheter is arranged.

[0084] The deflection control assembly comprises upper and lower control discs 210, 220 between which a pair of opposed disc dowel pins 230 are held in place. The interior discs are attached non-rotationally to the exterior deflection control member 200 by locking screw 240. A useroperatable disc / cap 245 is attached to the locking screw allowing a user to lock the control

[0085] 35 member 200 in a desired rotational position. For easy operation the control member is provided with an opposed pair of downwardly oriented arms 201 . A pair of opposed housing dowel pins 240047W001

[0086] 10

[0087] 130 are mounted in the housing just as the housing comprises a pair of anchor points 121 for the compression coils. Attachment of the pull wires to the deflection control assembly will be described below with reference to fig. 7.

[0088] 5 The flush assembly comprises a tubular flush hub 510 with a distal opening to which the guide catheter proximal end is fixedly attached. At the proximal end a flush manifold 520 provides fluid communication between the flush port 500 and the interior of the flush hub via flush tube 530. The proximal end of the flush hub is sealed with a gasket member 511 comprising a central opening allowing the delivery to pass through in sliding and sealing engagement. A

[0089] 10 couple of bracket members 540 position the flush hub inside the housing.

[0090] The combined control assembly comprises a generally tubular anchor member 310 with an axially extending bore and a distal thread 312 in engagement with the housing bore thread 112, the main proximal portion of the anchor member extending proximally from the housing bore. The generally tubular combined control member 300 is mounted in axially splined engagement with the anchor member and axially moveable thereon between a proximal and a distal position. The combined control member 300 comprises a distal circular opening rotation- ally and axially engaging the housing proximal portion 111. The anchor member 310 comprises a pair of opposed cut-outs 313 in the tubular wall in which a pair of clutch pins 320 are arranged, the clutch pins engaging a tubular elastomeric pinching clutch member 330 arranged in the anchor member bore to provide an actuatable clutch. The combined control member 300 further comprises a pair of opposed inner grooves 305 adapted to receive and actuate the clutch pins when the combined control member is moved between its proximal and a distal position as will be described in greater detail below.

[0091] 25

[0092] The handle 100 is adapted to receive the delivery catheter and provide axial and rotational control thereof. To provide support to the delivery catheter it is enforced by sections of hypotube bonded to the exterior thereof. A first section 410 of hypotube is provided on the delivery catheter portion running through the flush hub (see fig. 7), and a second section 420 of hypotube is provided on the portion running through the anchor member. The second section hypotube terminates proximally in an axial control member 430 allowing a user to grip and axially move the delivery catheter. On the second section hypotube 420 a stopper member 440 is arranged, the stopper member engaging axial stops in the anchor member bore to thereby limit axial movement of the delivery catheter between a fully retracted and a fully extended

[0093] 35 position. As shown in fig. 7 a gap 411 is formed between the first and second sections of hypotube, this allowing the ECG wire to be connected to the conducting delivery catheter core 240047W001

[0094] 11 member 22. A third section 450 of hypotube supports the delivery catheter between the axial control member 430 and the flush port 400. In an exemplary embodiment the first and second sections of hypotube are manufactured from SS304 and the third section is manufactured from a clear kink resistant polymer tube made of DEHP-Free PVC. Between the flush hub and the

[0095] 5 anchor member a support disc 340 for the delivery catheter is provided.

[0096] In fig. 7 the handle 100 is shown seen from below without the lower housing portion 120 and the lower control disc 220 mounted, however, in contrast to fig. 6 the guide catheter 10 and the delivery catheter 20 are shown. The guide catheter 10 enters the distal end of the handle

[0097] 10 and continues past the deflection control assembly to the flush hub 510 distal opening to which the guide catheter proximal end is fixedly attached. Corresponding to the distal end of the handle the guide catheter comprises a pair of opposed exit side openings 15A in communication with the corresponding tubular lumens 15 from which the compression coils and the therein arranged pull wires exit. In this way the integration of the guide catheter with the deflection control assembly respectively the flush hub is axially separated. The compression coils 16 proximal ends are attached to the anchor points 121 whereas the pull wires 17 are terminated as loops 17A using stainless crimp tubing 17B and continue in sliding engagement with the housing dowel pins 130 to the disc dowel pins 230 to which they are looped around. When the control discs are rotated via the deflection control member 200 a pulling respectively a pushing force are exerted on the distal pull ring 19 via the pull wires 17 causing the distal end of the guide catheter to deflect in a plane. For a desired degree of deflection, the deflection control member can be rotationally locked by tightening the locking screw 240.

[0098] In the middle portion of the handle the tubular flush hub 510 is mounted by brackets 540. The

[0099] 25 delivery catheter exits the guide catheter at the flush hub distal end, passes axially through the flush hub and exits through the gasket member 511. Corresponding to the flush hub and the gasket member the guide catheter is embedded in the first section 410 of hypotube. By this arrangement the cylindrical space between the guide and delivery catheter can be flushed from the flush port 500 via the flush tube 530, the flush manifold 520 and the flush hub 510. Corresponding to the flush hub the ECG wire connects to the conducting metallic core of the delivery catheter.

[0100] Proximally of the flush hub the delivery catheter passes through the anchor member 310 of the combined control assembly and exits the handle at the proximal end at which point it passes

[0101] 35 through the axial control member 430 to subsequently terminate at the injection port 400. The 240047W001

[0102] 12 functionality of the combined control assembly will be described in greater detail with reference to fig. 8.

[0103] As also described above with reference to fig. 6 the combined control assembly comprises a

[0104] 5 generally tubular anchor member 310 in threaded engagement with the housing. The anchor member comprises a pair of clutch pins 320 received in corresponding handle actuation grooves 305 serving to actuate the clutch by moving the clutch pins inwards by axial movement of the combined control member to thereby compress the clutch member 330. As the delivery catheter 20 passes through the tubular clutch member compression thereof will pinch the de¬

[0105] 10 livery catheter and thus hold it axially and rotationally in place relative to the anchor member. Correspondingly, the combined control member can be moved axially to release pressure on the clutch pins and thereby also the clutch member 330, this releasing the holding grip on the delivery catheter allowing it to move axially and rotationally relative to the anchor member. In the shown embodiment axial movement of the combined control member is limited by the length of the groove 305 traveling over the clutch pins 320. During assembly the combined control member is mounted on the housing by axially forcing the combined control member distally over the clutch pins and the elastomeric clutch member 330.

[0106] In the shown embodiment the combined control member has a first axial position in which the fluid delivery catheter is axially and rotationally locked relative to the anchor member (and thus the housing and the guide catheter) and in which rotational movement of the control member causes rotational movement of the fluid delivery catheter, and a second axial position in which the fluid delivery catheter is axially and rotationally free relative to the housing and thus the guide catheter, this allowing the delivery catheter to be moved axially (and rotationally) by

[0107] 25 means of the axial control member 430, the amount of axial movement being limited by the distal and proximal stop surfaces engaging the stopper member 440 inside the anchor member. In the shown embodiment the first axial position is a distal-most position of the combined control member relative to the housing and the second axial position is a proximal-most position of the combined control member relative to the housing.

[0108] As follows from the treaded engagement 112, 312 between the anchor member and the housing, when the combined control member is in the first axial position, the clutch is actuated and the fluid delivery catheter is coupled axially and rotationally locked to the anchor member, whereby rotational movement of the combined control member causes axial movement of the

[0109] 35 “axially locked” fluid delivery device corresponding to the threaded engagement between the anchor member and the housing. In an exemplary embodiment the threaded engagement 240047W001

[0110] 13 between the anchor member and the housing has the same pitch as the helical needle whereby rotation of the combined control member is transferred 1 :1 to the helical needle. Correspondingly, the length of the thread may correspond to the length of the helical needle.

[0111] 5 In a situation of use the catheter assembly is prepared before operation by moving the combined control member to its second axial position to unlock the clutch, this allowing the helical needle to be moved axially to its fully retracted position inside the distal cavity of the guide catheter, and the anchor member to be rotated to its proximal-most position. When this is assured the combined control member is moved to its first axial position to lock the clutch.

[0112] 10 Fluid may be introduced through the flush port and the injection port to purge air from the catheter assembly. As the fluid contained in the delivery catheter represents a dead space for the treatment fluid or fluid suspension to be introduced into the target tissue via the helical needle, the guide catheter may be loaded with the treatment fluid at this point. Alternatively, the dead space may be purged just prior to the helical needle being advanced into the target tissue. In an aspect of the invention a suspension transfer device is provided which will be described below.

[0113] The catheter is now ready for introduction into the vasculature of a patient. Using the flexibility, pushability, torqueability and the ability to control and lock deflection of the distal tip of the guide catheter, the skilled surgeon will manoeuvre the distal end of the guide catheter into the vicinity of the treatment site, e.g. at a desired location in the heart for subsequent injection of cardiomyocytes into the myocardium. At this point, the operator will release the clutch and move / push the helical needle axially out of the guide catheter and into contact with a desired myocardial surface area of the moving heart. To help position the helical needle precisely, the

[0114] 25 operator may be guided by ECG signals picked up by the catheter distal tip. After re-engaging the clutch, the combined control member can be used to rotate the delivery catheter and thus the helical needle into the myocardium, the rotational and axial movement of the helical needle being determined by the pitch and length of the threaded engagement between the anchor member and the handle housing.

[0115] Turning to figs. 9 and 10 an exemplary embodiment of a suspension transfer device, or “dose control kit” will be scribed.

[0116] The suspension transfer device 700 comprises a syringe barrel 710 comprising a proximal

[0117] 35 main portion 711 with a cylindrical inner surface defining a variable volume main chamber 718, a distal transfer opening 715, and a distal transfer portion 712 with an inner surface which 240047W001

[0118] 14 smoothly and positively tapers towards the distal transfer opening. In the present context the reduced cross-sectional area in the direction from the cylindrical portion towards the transfer opening defines a positive taper, no taper being 0 degrees. In exemplary embodiments the positive taper is less than 20 degrees, less than 10 degrees or less than 5 degrees from the

[0119] 5 centre axis of the syringe, i.e. a total taper for the transfer portion of less than 40 degrees, less than 20 degrees or less than 10 degrees. The taper may be straight in case of the transfer portion having a conical shape. Alternatively, if the taper is curved (as in the embodiment shown in fig. 11) the taper may refer to the average taper. In the shown embodiment the transfer portion is conical with a taper of 5 degrees from the centre axis of the syringe and thus a

[0120] 10 total taper for the transfer portion of 10 degrees.

[0121] The syringe barrel comprises at the distal end a coupling portion 716 (here a male Luer coupling) allowing the transfer device to be initially connected to a fluid / cell source and subsequently to a fluid receiving device, e.g. the injection port 400 of the above-described catheter assembly 1. The cylindrical main portion comprises a proximal opening 717 adapted to receive a piston. The suspension transfer device further comprises a piston 720 arranged in sliding and sealing engagement with the cylindrical inner surface to define a variable volume main chamber, and a piston rod 730 having a distal end to which the piston is attached and a proximal end with a handle disc 731. The syringe barrel is provided with a pair of proximally extending flanges 716 cooperating with the handle disc 731 to limit distal movement of the piston. In the shown embodiment the main portion and the transfer portion are formed as an integral component with a smooth transition between the respective inner surfaces. The barrel main portion may be provided with indices (not shown) to help identify the exact position of the piston during loading and expelling of fluid suspensions. The taper of the distal transfer portion and

[0122] 25 the smooth transition between the two portions ensure that when a suspension of e.g. cells or cell agglomerates have been transferred to the syringe barrel, e.g. through suction via the transfer opening, and collected in the transfer portion, e.g. through vertical sedimentation, then the cells or cell agglomerates can be purged into (in the present context) the delivery catheter with only a minimal loss of cells or cell agglomerates, this in contrast to a traditional syringe set-up in which a larger portion of the cells or cell agglomerates would be trapped in corners and at edges.

[0123] Fig. 11 shows an alternative embodiment of a transfer system in which the transfer portion is provided as a separate transfer member 800 comprising an intermediate portion 813 arranged

[0124] 35 between the proximal main portion (e.g. in the form of a separate syringe, not shown) and the distal transfer 812 portion, wherein the inner surface of the intermediate portion smoothly and 240047W001

[0125] 15 negatively tapers towards the distal transfer portion inner surface, the intermediate and distal portions thereby forming a bulbous combined transfer portion 814. To enlarge the volume of the suspension transfer device without increasing the outer diameter the bulbous transfer portion may comprise a non-tapered, e.g. cylindrical, portion between the tapered distal and in¬

[0126] 5 termediate portions.

[0127] The transfer member 800 comprises a distal transfer opening 815 with a threaded connector 816 (here a male threaded luer lock connector), and a proximal opening 811 with a threaded connector 819 (here a female threaded luer lock connector) adapted to be connected to a

[0128] 10 proximal main portion in the form of a traditional syringe comprising a mating connector. As appears from fig. 11 the transfer portion has a non-straight taper.

[0129] During initial preparation for delivery of e.g. a cell suspension to a treatment site using the above-described catheter assembly 1 , an amount of a cell suspension comprising a known volume of cells or cell agglomerates is transferred to the transfer device 700, 800 by withdrawing the piston rod to fill the transfer portion and the main portion with cell suspension. Positioning the transfer device vertically will allow the cells or cell agglomerates to fully or partly sediment in the transfer portion. In an exemplary use of the transfer device the volume of cells or cell agglomerates is smaller than the volume of the transfer portion.

[0130] When the cells or cell agglomerates have collected in the transfer portion, the transfer portion is connected to the injection port 400 (see fig. 1) and the known volume of collected cells or cell agglomerates can be transferred to the delivery catheter. As the inner diameter and the length of the delivery catheter lumen is known it can be calculated at which position the distal-

[0131] 25 most portion of the cells or cell agglomerates are positioned in the inner fluid transmission lumen 21 , this allowing the cells or cell agglomerates to be moved distally into the vicinity of the helical needle by injecting a metered amount of fluid from the transfer device main portion.

[0132] In the above description of exemplary embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.

[0133] 35 *****

Claims

240047W00116CLAIMS1. A catheter assembly (1) comprising: i) a guide catheter (10) comprising:5 a tubular wall (11) defining a central lumen (12), a free portion with a distal end, and a proximal handle portion, a pair of opposed wire lumens (15) arranged in the tubular wall, a pair of opposed exit side openings (15A) in communication with respective wire10 lumens and arranged in the proximal handle portion, and a pair of opposed control wires (17), each control wire having a main portion guided in a respective wire lumen (15), a distal end anchored distally in the tubular wall (19), and a proximal end portion exiting from the wire lumen via the exit side opening,(ii) a delivery catheter (20) with a central lumen (21), comprising: a main portion arranged axially and rotationally moveable in the guide catheter (10) central lumen (12), and a proximal portion with a proximal fluid inlet (400), iii) a handle (100) in which the guide catheter proximal handle portion is arranged and from which the guide catheter free portion extends, comprising: a housing (110, 120), and25 deflection control means (200, 210, 230) attached to the control wire proximal end portions (17A) and adapted to exert an axial pull or push force to the control wires to thereby deflect the distal end of the guide catheter, wherein: the guide catheter (10) has a proximal fluid inlet end arranged within the housing and from which the delivery catheter (20) proximal portion exits, and the delivery catheter proximal portion exits from the housing,(iv) a flush hub (510) arranged in the housing, comprising:35 a distal end attached to the guide catheter (10) and sealingly surrounding the guide catheter proximal fluid inlet,240047W00117 a proximal sealing valve (511) from which the delivery catheter proximal portion exits, the sealing valve allowing axial and rotational movement of the delivery catheter relative to the flush hub (510) and thus the guide catheter, and a flush port (500) in fluid communication (520, 530) with an interior of the flush hub5 (510), whereby the axially extending space (12A) between the delivery catheter (20) and the guide catheter (10) can be flushed with a fluid via the flush port (500).10 2. A catheter assembly as in claim 1 , wherein: the deflection control means comprises a control member (200) arranged rotatable relative to the housing, and the control wires (17) are attached to the control member such that rotation of the control member relative to the housing causes a pulling respectively a pushing force to be applied to the pair of control wires.

3. A catheter assembly as in claim 1 or 2, further comprising: a tubular compression coil (16) arranged in each of the wire lumens to axially surround and support the respective control wires (17) along at least a portion of their length.

4. A catheter assembly as in claim 3, wherein each compression coil comprises a free proximal coil portion exiting from the corresponding wire lumen via the exit side opening, each25 proximal coil portion surrounding a portion of a control wire proximal end portion and being attached (121) to the handle housing.

5. A catheter assembly as in any of claims 1-4, wherein the guide catheter proximal fluid inlet end is arranged in the housing proximally of the control means.

6. A catheter assembly as in any of claims 1-5, wherein the delivery catheter (20) cannot be removed from the guide catheter.

7. A catheter assembly as in claim 6, wherein:35 the guide catheter free portion comprises:240047W00118 a main portion with the pair of opposed control wires (17), the central lumen (12) having a first diameter, and a distal portion (13) having a tubular wall forming a distal cavity (14) with a second larger diameter, and5 the delivery catheter comprises: a distal hollow helical needle (30) in fluid communication with the delivery catheter central lumen (21), the hollow helical needle having an outer diameter smaller than the second diameter but larger than the first diameter, the hollow helical needle comprising one or more outlet openings (32) and being moveable from a retracted position arranged within the cavity (14) to an extended position projecting from the cavity.

8. A catheter assembly as in any of claims 1-7, the handle (100) further comprising:15 a control member (300), and a clutch (330) operatable between:(a) an unlocked state in which the delivery catheter can be moved axially relative to the guide catheter, and20 (b) a locked state in which the delivery catheter cannot be moved axially relative to the guide catheter yet can be rotated relative to the guide catheter by rotation of the control member relative to the housing.

9. A catheter assembly as in claim 8, wherein the clutch is operatable between the unlocked state and the locked state by axial movement of the control member relative to the housing.*****

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