Systems and methods to sense characteristics of a therapeutic agent in vivo
Systems and methods are provided for delivering a therapeutic agent to a target tissue via a vessel and sensing, in vivo, a characteristic of the therapeutic agent in the vessel. The characteristic indicates a concentration of the therapeutic agent in the vessel. The system preferably includes an occluder. The method preferably includes infusing the therapeutic agent distal of the occluder while the occluder is in an expanded configuration in the vessel.
1 . A system for temporarily occluding a target vessel in a patient during infusion of a solution of a therapeutic agent to the patient, comprising:
a) a flexible inner tubular member comprising a proximal end, a distal end, and an infusion lumen extending between the proximal and distal ends, the infusion lumen opening to a distal orifice at the distal end of the flexible inner tubular member;
b) an outer catheter comprising a proximal end, a distal end, and a flush lumen defined between the flexible inner tubular member and the outer catheter, the flush lumen opening to a distal aperture at the distal end of the flush lumen;
c) an expandable occluder at the distal end of the outer catheter, the expandable occluder having a collapsed configuration for advancement through the target vessel and an expanded configuration for occluding the target vessel, wherein the expandable occluder is proximal of the distal orifice of the flexible inner tubular member;
d) a pressure sensor in fluid communication with the flush lumen, the pressure sensor configured to sense, with a delay in response time, in vivo fluid pressure distal of the expandable occluder,
wherein the pressure sensor is located proximal of the distal aperture at a distance such that the delay in response time is suitably short for the pressure sensor to monitor pressure changes during the infusion of the solution, the delay in response time corresponding to a cross-sectional area of the flush lumen and the distance between the pressure sensor and the distal aperture; and
e) a delivery system comprising a controller and an infusion pump, the delivery system configured to deliver the solution of the therapeutic agent at an infusion rate through the infusion lumen of the flexible inner tubular member and to the target vessel until the pressure sensor senses that the fluid pressure distal of the expandable occluder has stabilized, wherein the delivery system allows the solution of the therapeutic agent to dwell within the target vessel for a period of a dwell time after infusion while the expandable occluder remains in the expanded configuration,
wherein the controller determines the dwell time as a function of a pressure differential between a first pressure distal of the expandable occluder sensed by the pressure sensor when the expandable occluder is in the collapsed configuration, and a second pressure distal of the expandable occluder sensed by the pressure sensor when the expandable occluder is in the expanded configuration.
2 . The system of claim 1 , further comprising f) a fluid evacuation system to remove at least a portion of the delivered solution of the therapeutic agent from the patient through an evacuation lumen while the expandable occluder is in the expanded configuration.
3 . The system of claim 1 , wherein the controller determines the dwell time as a period for the solution to dwell in the vessel that optimizes filtration of the therapeutic agent from the solution into a target tissue based on the pressure differential between the first and second pressures distal of the expandable occluder sensed by the pressure sensor.
4 . The system of claim 1 , wherein the sensor is located from 50 cm to 100 cm away from the distal aperture of the flush lumen.
5 . The system of claim 1 , wherein the cross-sectional area of the flush lumen is 0.5 mm 2 and the delay in response time of the sensor is 2-5 seconds.
6 . The system of claim 1 , wherein the cross-sectional area of the distal aperture of the flush lumen is 0.5 mm 2 and the delay in response time of the sensor is 1-3 seconds.
7 . The system of claim 1 , wherein the cross-sectional area of the flush lumen is 2 mm 2 and the delay in response time of the sensor is 0.1-0.5 seconds.
8 . The system of claim 1 , wherein the pressure sensor is configured to continually sense, with the delay in response time, the in vivo fluid pressure distal of the expandable occluder.
9 . The system of claim 1 , wherein the expandable occluder comprises an inflatable occlusion balloon and the sensor is in pressure communication with a distal side of the inflatable occlusion balloon.
10 . The system of claim 1 , wherein the expandable occluder comprises a microvalve comprising a proximal end coupled to the distal end of the outer catheter, a distal end coupled to the distal end of the flexible inner tubular member, a fluid permeable coating over a distal portion of the expandable occluder.
11 . The system of claim 10 , wherein the fluid permeable coating membrane comprises pores configured to dampen pressure fluctuations sensed by the pressure sensor and the response time of the sensor is 0.2-1 seconds.
12 . The system of claim 10 , wherein the pores are configured to dampen pressure fluctuations sensed by the pressure sensor and the response time of the sensor is 0.01-0.2 seconds.
13 . The system of claim 1 , further comprising a side port in fluid communication with the flush lumen, wherein the sensor is located at the side port.
14 . The system of claim 1 , wherein the delay in response time is at or less than 5 seconds.
15 . The system of claim 1 , wherein the controller determines the dwell time as a period for the solution to dwell in the vessel that optimizes diffusion of the therapeutic agent from the solution across a wall of the target vessel.