Microfluidic drug delivery devices with venturi effect
The methods, systems, and devices disclosed herein generally involve convection-enhanced delivery of drugs to a target region within a patient. Microfluidic catheter devices are disclosed that are particularly suitable for targeted delivery of drugs via convection, including devices capable of multi-directional drug delivery, devices that control fluid pressure and velocity using the venturi effect, and devices that include conformable balloons. Methods of treating various diseases using such devices are also disclosed, including methods of treating cerebral and spinal cavernous malformations, cavernomas, and hemangiomas, methods of treating neurological diseases, methods of treatment using multiple microfluidic delivery devices, methods of treating hearing disorders, methods of spinal drug delivery using microfluidic devices, and methods of delivering stem cells and therapeutics during fetal surgery. Methods of manufacturing such devices are also disclosed.
1. A microfluidic convection-enhanced-delivery (CED) device, comprising:
a shank portion;
at least one fluid delivery conduit having a proximal end, a distal end, a fluid inlet port, and at least one fluid outlet port, the at least one fluid delivery conduit being formed in or on the shank portion, the at least one fluid delivery conduit comprising first and second upstream lumens and a single downstream lumen;
a flow restriction formed within the at least one fluid delivery conduit at a merge of the first and second upstream lumens into the single downstream lumen, the flow restriction being configured to adjust a pressure of fluid being directed through the at least one fluid delivery conduit;
wherein the flow restriction comprises a constricted region of the at least one fluid delivery conduit having a cross-sectional area that is less than a cross-sectional area of a proximally-adjacent portion of the at least one fluid delivery conduit;
wherein the at least one fluid outlet port includes a plurality of fluid outlet ports formed in the first and second upstream lumens and a plurality of fluid outlet ports formed in the single downstream lumen; and
wherein the plurality of fluid outlet ports formed in the first and second upstream lumens are formed in an outermost surface of the microfluidic CED device and disposed such that fluid exits from the first and second upstream lumens directly to a location exterior to the microfluidic CED device.
2. The device of claim 1 , further comprising an insertion support scaffold to which the shank portion is coupled.
3. The device of claim 1 , wherein the shank portion is formed from silicon and the at least one fluid delivery conduit is formed from parylene.
4. The device of claim 1 , wherein the cross-sectional area of the constricted region is at least about 20% less than the cross-sectional area of the proximally-adjacent portion.
5. The device of claim 1 , wherein the cross-sectional area of the constricted region is at least about 30% less than the cross-sectional area of the proximally-adjacent portion.
6. The device of claim 1 , wherein the cross-sectional area of the constricted region is at least about 40% less than the cross-sectional area of the proximally-adjacent portion.
7. The device of claim 1 , wherein the proximally-adjacent portion has a height between about 1 micron and about 50 microns and the constricted region has a height between about 1 micron and about 25 microns.
8. The device of claim 1 , wherein the proximally-adjacent portion has a width between about 10 microns and about 100 microns and the constricted region has a width between about 5 microns and about 50 microns.
9. The device of claim 1 , wherein the at least one fluid outlet port comprises a wherein the plurality of fluid outlet ports are spaced a distance apart from one another between the proximal and distal ends of the at least one fluid delivery conduit.
10. The device of claim 9 , wherein each fluid outlet port of the plurality of fluid outlet ports has an area that is great than an area of any of the plurality of fluid outlet ports positioned proximally thereto.
11. The device of claim 1 , wherein the at least one fluid delivery conduit is formed from at least one of a parylene composition, a silastic composition, a polyurethane composition, and a PTFE composition.
12. The device of claim 1 , further comprising a fluid reservoir in fluid communication with the fluid inlet port of the at least one fluid delivery conduit and configured to supply a fluid thereto under positive pressure.
13. The device of claim 1 , wherein the at least one fluid delivery conduit comprises an embedded microsensor.
14. The device of claim 13 , wherein the embedded microsensor comprises at least one of an interrogatable sensor, a pressure sensor, a glutamate sensor, a pH sensor, a temperature sensor, an ion concentration sensor, a carbon dioxide sensor, an oxygen sensor, and a lactate sensor.
15. The device of claim 1 , wherein the at least one fluid delivery conduit is configured to aspirate fluids.