Barrier coating on blood contacting devices

A blood pressure monitoring device includes a pressure sensing element mounted or a probe tip or in a catheter tip adapted for insertion into a patient's blood stream. The element includes a pressure transducer having a micromachined diaphragm which flexes in response to pressure changes. The flexes are converted by the transducer to electrical signals which pass back through the catheter to a display. The element and the catheter are conformally coated with a thin layer of parylene which insulates the device from the deleterious effects which blood components such as water and ions would otherwise have on various components of the device.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to implantable biomedical devices, and more 
particularly, relates to blood contacting sensing devices and a method for 
their protection against degradation induced by the blood. 
2. Background of the Invention 
In current diagnostic and therapeutic medical practice, many situations 
arise in which an instrument must be implanted and maintained in a 
patient's body for extended periods of time. For example, implanted 
sensors for gases, electrolytes and pH which depend on a component of a 
body fluid reaching the sensor for a chemical reaction are well-known. 
In other cases, the sensor measures a physical effect, such as blood 
pressure, by converting a pressure flex on the sensor to an electrical 
charge. In these cases, it is often essential that the body fluid be 
prevented from contacting the sensing element, because body fluids in 
general contain ions in an aqueous environment, and ions and other 
constituents of body fluids are often deleterious to the sensing element 
particularly when an electrical charge is to be developed. In addition, 
water vapor passes easily through most materials and itself catalyses 
reactions that may corrode various device components. 
Exemplary of devices adapted for implantation is that described by Wallace 
et al. in U.S. Pat. No. 4,785,822. The Wallace et al. device includes a 
pressure transducer covered by a cap for monitoring pressure in body 
compartments such as the uterus. The transducer and cap are disposed in a 
flexible boot, and aligned hole in the cap and boot are filled with a 
silicone gel. The gel serves as a hydraulic fluid which transmits external 
pressure in the body compartment to the transducer and also provides a 
water tight seal to prevent body fluid from reaching the transducer. 
Hutchins et al., in U.S. Pat. No. 3,710,781, discloses a catheter tip 
pressure transducer for blood pressure measurement. The transducer is 
covered by a rubber sheath which provides a seal against entrance of the 
blood into the transducer compartment. 
Protection of implants from damage by body fluids has been summarized by 
Troyk in Sensors Expo Proceedings, 1988, page 308A-1. Troyk discusses the 
state of the art in packaging for implantable sensors, and states that, 
while blood compatible chemical sensors have been developed, they cannot 
be used with implanted systems because of packaging difficulties. 
Coatings have been extensively studied for the protection of implants. 
Matsuo et al., in Sensors and Activators, 9, 115 (1986) discloses a 
parylene-coated reference ion sensitive field effect transistor fabricated 
by cleaning of the silicon surface with an oxygen plasma and depositing a 
100 nm parylene coating thereon. 
Yasuda et al., in Biomedical Sciences Instrumentation, 17, 109 (1981), 
reports that vapor deposited parylene coating adhere well to polymeric 
surfaces but poorly to metal and glass, and that the poor adhesion to 
metal and glass may be overcome by glow discharge depositing a primer 
coating of polymer and vapor depositing a coating of parylene over the 
polymer. Similarly, Nichols et al., in Biomedical Sciences 
Instrumentation, 23, 57 (1987), states that no single off-the-shelf 
polymeric material has sufficient biocompatibility and adherence to 
various implant materials to provide insulation to a sensor exposed to the 
hostile ionic environment of extracellular fluid. Thus, Nichols et al. 
teaches a trilayer coating for sensor implants consisting of a first glow 
discharge polymerized and deposited layer of methane, a second layer of 
glow discharge polymerized and deposited parylene C thereon and an outside 
layer of biocompatible parylene C vapor deposited thereon. 
Blood contacting medical implants face the additional problem of the 
thrombogenicity associated with most foreign materials in contact with the 
blood. Kanda et al., in Electronic Letters, 17, 558 (1981) discloses a 
study of clotting times of various surfaces in contact with blood. 
Much effort has been expended by many workers in an effort to construct a 
direct blood contacting device which can be implanted in a patient's blood 
stream and provide continuous blood pressure monitoring for a protracted 
period of time without sustaining damage or inducing thrombosis. While the 
above disclosures have addressed the problem, to date, no such device 
exists. The present invention provides a solution to this problem. 
SUMMARY OF THE INVENTION 
A pressure monitoring device includes a pressure sensing element having a 
pressure transducer mounted in a catheter tip. The element senses pressure 
changes and the transducer converts the changes to signals which are 
connected through the catheter to a display. The element and at least a 
portion of the catheter are coated conformally with a thin layer of 
parylene. (In the present disclosure, the term conformally means a 
continuous pinhole-free covering over all surfaces, joints and 
connections). 
In a preferred device of the invention for blood pressure monitoring, the 
transducer is supported in an end cap affixed to the end of the catheter. 
The transducer is separated from a patient's blood by a micromachined 
diaphragm which flexes in response to changes in the blood pressure. The 
flexes are converted by the transducer to electrical signals which pass 
through a conductor, such as a wire back through the catheter to the 
monitor. Preferably, air communication is maintained between the interior 
of the catheter and the exterior surface of the diaphragm. 
The preferred conformal coating of parylene is applied by vapor deposition 
and is from about 2 to 10.mu. thick. 
Thus, the present invention provides a catheter tip blood pressure 
monitoring device in which a thin vapor-deposited pinhole-free layer of 
parylene is conformally coated directly onto the pressure sensing element 
and at least a portion of the catheter. Because the coating is very thin, 
it protects the sensing element without compromising the flexional 
properties of the diaphragm. The coating is applied directly onto the 
element and catheter with a need for a primer coat. Because the parylene 
coating adheres exceptionally firmly to the polymeric catheter and 
conformally covers both the catheter and the element, the coating has no 
tendency to delaminate from the nonpolymeric portions of the element, such 
as the transducer and end cap. Thus, the device may be maintained in a 
patient's blood stream for a week or more with swelling, cracking, leaking 
or delaminating. By coating a blood contacting implant with parylene in 
accordance with the invention, the need for an anticoagulent, such as 
heparin, may be eliminated for up to two weeks. On the other hand, a 
heparin layer may be applied to the parylene coating if desired to further 
enhance antithrombogenicity, particularly if the device is to remain 
implanted in a patient's blood stream for longer periods.

DETAILED DESCRIPTION 
While this invention is satisfied by embodiments in many different forms, 
there will herein be described in detail preferred embodiments of the 
invention, with the understanding that the present disclosure is to be 
considered as exemplary of the principles of the invention and is not 
intended to limit the invention to the embodiments illustrated and 
described. The scope of the invention will be measured by the appended 
claims and their equivalents. 
In its broadest scope, the present invention is contemplated to include any 
implantable sensing device conformally coated with vapor-deposited 
parylene directly onto the device surface. Preferred sensing devices of 
the invention are catheter tip sensors responsive to physical effects, 
such as pressure, useful for measuring pressure changes in a compartment 
of a living body. Particularly preferred is a catheter tip blood pressure 
measuring device. 
A preferred parylene coated catheter tip pressure sensing device of the 
invention will now be described in general terms with reference to the 
drawings. A detailed description of the preferred device absent the 
parylene coating is provided in copending application, Ser. No. 410,564, 
filed Sept. 21, 1989, of common assignee, which copending application is 
herein incorporated by reference. 
FIG. 1 illustrates blood pressure sensing device 10 including catheter 12 
having proximal end 14 and distal end 16. A pressure sensor 18 is mounted 
in distal end 16, and proximal end 14 is connected to a display monitor 
20. Any electronics necessary for conversion of pressure sensed by sensor 
18 to the monitor may be housed in a suitable enclosure 22 between the 
sensor and monitor. If desired, the device may include an optional blood 
sample port 24 connected to the catheter by a conventional luer-lok 26. 
Distal end 16 of catheter 12, including that portion of the catheter which 
includes sensor 18, is conformally covered with a coating of parylene 28. 
FIG. 2 shows parylene coating 28 conformally covering sensor 18 and a 
portion of catheter 12. It is evident that the parylene coating may be 
applied to only a portion of the catheter, as shown in FIG. 2, or it may 
cover the entire portion of the catheter contemplated to be inserted into 
a patient. 
FIG. 3 illustrates one embodiment of a blood pressure sensing device 
suitable for application of the parylene coating of the invention. 
Pressure sensor 18 includes a silicon transducer 40 micromachined to 
include a cavity 42 and a diaphragm 44 which forms the bottom wall of the 
transducer. A plurality of bonding pads 46 of a conducting metal are 
affixed to a surface of transducer 40. The transducer is affixed firmly, 
as for example by an adhesive 47 to an end cap 49 having a shoulder 50, a 
wall 52 and a flange 54. Catheter 12 may be mounted on flange 54 to abut 
shoulder 50 and may be affixed to both with adhesive 47. 
A vent tube 56 passes through wall 52 to provide air communication for 
pressure equalization between the bottom surface of diaphragm 44 and the 
interior of catheter 12. A plurality of conductors 58 likewise pass 
through wall 52 and connect to bonding pads 46. A coating 59 of a suitable 
insulating material may be applied to a surface of transducer 40, pads 46 
and conductors 58. An adhesive fill 60 may be added to the interior space 
bounded by flange 54 to provide support for tube 56 and conductors 58. 
Any suitable polymer which can be extruded by either melt or solution 
techniques may be used for fabrication of catheter 12. Suitable polymers 
are, for example, polyethylene, polypropylene, polyvinyl acetate, 
polyester or preferably polyurethane or copolymers thereof. 
Diaphragm 44 may be about 1 to 10, preferably about 6.mu. thick. While it 
is preferred that the diaphragm is an integral part of the silicon 
transducer formed by micromachining to form cavity 42, it is apparent to 
one skilled in the art that the diaphragm may also be a membrane of a 
material such as rubber. 
Bonding pads 46 serve to establish electrical communication between 
conductors 58 and transducer 40 and may be of any conducting metal. 
Suitable conducting metals are silver, gold or preferably aluminum. 
Coating 59 may be of any suitable insulating material, preferably silicon 
nitride. The coating may be applied by any suitable procedure, as for 
example from a solvent solution followed by solvent evaporation, or, 
preferably it may be sputter coated to the surface of transducer 40, pads 
46 and conductors 58. 
End cap 49 closes the distal end of catheter 12 and provides support for 
transducer 40. The end cap may be ceramic or preferably a metal, most 
preferably stainless steel. 
Conductors 58 pass through catheter 12 to provide electrical communication 
from transducer 40 through pads 46 to the electronics in enclosure 22. The 
conductors, preferably a plurality of wires, may be of any suitable 
material for conducting electrical signals such as platinum, copper, or, 
preferably aluminum. Most preferably, the conductors are coated with a 
layer of a suitable insulator, such as epoxy or crosslinked polyurethane. 
Parylene is the generic name for thermoplastic film polymers based on para 
xylylene. Three precursor xylylene dimers commercially available from 
Nova-tran Corp., Clearlake, Wisc., may be polymerized to polymers 
conventionally referred to as parylene N, parylene D and parylene C, and 
the present invention contemplates coatings from all three. The preferred 
coating material of the invention is parylene C. This product is prepared 
by heating 2-chloro-p-xylylene in steam to a high temperature to produce a 
solid cyclic dimer which can be isolated in pure form. The pure dimer is 
then pyrolyzed to two molecules of a monomeric highly reactive 
intermediate .alpha.,.alpha.'-diradical of chloro-p-xylylene. On cooling, 
the vaporized diradical condenses on the object as a conformal coating of 
polymeric film in a process generally referred to as chemical vapor 
deposition. 
The parylene coating may be deposited on the pressure sensing device of the 
invention in a suitable pyrolysis apparatus having a sublimination 
chamber, a pyrolysis chamber and a deposition chamber, as for example the 
Model 1050 parylene generator available from Nova-tran. The solid dimer 
may be placed in the sublimination chamber and the device to be coated may 
be placed in the deposition chamber. The apparatus may be pumped down to a 
pressure of about 1 to 100, preferably about 10 to 30 millitorr using a 
mechanical pump and a liquid nitrogen trap. The temperature of the 
sublimation chamber may be raised to about 50.degree. to 300.degree. C., 
preferably about 100.degree. to 200.degree. C., most preferably about 
150.degree. C. whereby the dimer sublimes and the vapor passes into the 
pyrolysis chamber. Pyrolysis of the vaporized dimer may be carried out by 
maintaining the temperature of the pyrolysis zone about 500.degree. to 
900.degree. C., preferably about 600.degree. to 800.degree. C., most 
preferably about 650.degree. C. The diradical formed by the pyrolysis 
passes into the deposition chamber where it polymerizes and condenses 
conformally on all surfaces of the device. 
It has been found that the temperatures maintained in the sublimation and 
pyrolysis chambers and the pumpdown pressure are factors in control of the 
rate at which the coating forms on the device. Higher temperatures and 
lower pressures increase the rate of coating formation. Accordingly, 
coatings which range in thickness from about 0.25 to 25.mu. may be 
deposited in about 10 sec to 10 hr. Preferred coatings are about 1 to 
15.mu. thick and are deposited in about 1 to 60 min. The most preferred 
coatings are about 2 to 10.mu. thick and are formed in about 30 min. 
It is known that parylene adheres well to polymeric materials and, in 
accordance with the invention, it has been found that the parylene coating 
adheres exceptionally well to the surface of the polyurethane catheter. 
The firmly adhered coating on the catheter portion of the device anchors 
the conformal coating so that the portion of the coating on the metal end 
cap does not undergo any delamination in spite of the well-known failure 
of parylene to adhere to metal or glass surfaces. 
The morphology of the parylene coatings on the catheter tip probes of the 
invention were analyzed by scanning electron microscopy (SEM) and found to 
vary in thickness from 1 to 45.mu. in thickness depending on the quantity 
of dimer charged to the sublimation zone of the reactor and the volume of 
the reactor. Thus, a dimer mass of 2.6 g in a 169.6 cubic inch reactor and 
a dimer mass of 3.1 g in a 339.3 cubic inch reaction gave a film 2 to 
5.mu. thick. 
In accordance with the invention, a catheter tip probe having a 2.54.mu. 
coating of parylene C, after 8 days implantation in a rabbit artery, was 
devoid of degradation, as described in Example III and illustrated in the 
photograph of FIG. 6. This probe was fully functional after the 8 days and 
clearly would have remained so for an indefinite period if the 
implantation has been maintained. In contrast, an identical probe lacking 
the parylene coating showed extensive decomposition after 30 minutes 
immersion in 1N saline, conditions which approximate blood in 
corrosiveness, as shown in FIG. 5. 
The parylene coated probe of the invention remained substantially 
nonthrombogenic for the 8 day rabbit implantation. If deemed appropriate, 
the parylene coated probe may be coated with an anticoagulent to further 
protect against the formation of thrombi when placed in a patient's blood 
stream. A preferred anticoagulent is heparin, which may be applied by any 
conventional process. For example, a suitable method for heparinization of 
a blood contacting surface is that of Dudley et al. U.S. Pat. No. 
4,349,467 in which the surface is treated sequentially with a cationic 
surface active agent and sodium heparin. 
The following Examples are provided to further describe the invention but 
are not to be considered in any way as limitative of the invention. 
EXAMPLE I 
General Procedure for Parylene Coating 
The catheter tip blood pressure probe to be parylene coated was placed in 
the deposition chamber of the Nova-tran Model 1050 reactor. The reactor 
was sealed and the appropriate amount of parylene C dimer (i.e., for a 
desired coating thickness) was uniformly distributed in the sublimation 
zone of the reactor. The system was pumped down to a partial pressure of 
50 mTorr and liquid nitrogen was added to the cold trap to serve as both a 
trap and a cryopump. Pumping was continued until a partial pressure of 20 
mTorr or less was achieved. 
The pyrolysis zone heater was then turned on and the temperature raised to 
655.degree. C. over several min. The sublimation zone heater was then 
heated to 155.degree. over 10 to 15 min and maintained at this temperature 
for 30 min. The sublimation and pyrolysis zones were cooled to room 
temperature, the liquid nitrogen was removed from the trap, air was bled 
into the system and the probes were removed. Film thickness and quality 
(i.e., absence of pinholes) was determined by SEM. 
EXAMPLE II 
The catheter tip blood pressure probe of FIGS. 2 and 3 but lacking the 
parylene coating was immersed in a 1N saline both for 1 hour at 37.degree. 
C. The probe was removed from the bath, rinsed thoroughly with distilled 
water, dried and examined. An optical micrograph showed extensive 
degradation of the bonding pads and conductors, as shown in FIG. 5. 
EXAMPLE III 
A parylene-coated catheter tip blood pressure probe as illustrated in FIGS. 
1-3 was inserted into the artery of a rabbit. The probe was removed after 
8 days and examined visually and by SEM for degradation of the sensor 
element and conductors due to the blood. The probe showed no degradation, 
as shown in FIG. 6 and was fully functional in monitoring blood pressure. 
Thus, the invention provides a catheter tip blood pressure monitoring 
device in which the sensitive components are protected against moisture 
and ions by a conformal coating of parylene firmly adhered to the 
polymeric catheter so that delamination of the parylene from the 
non-polymeric sensing element does not occur.