Medical Microbubble Generation

Abstract

Medical apparatus and processes controllably generate medically useful micro or nano bubbles of medically desirable and controllably selectable size, size distribution, homogeneity and concentration (and/or other key bubble parameters) for patient infusion, and/or which may incorporate therapeutic or other agents for patient infusion and/or may be combined with therapeutic or other agents prior to infusion into patients. The bubble generation apparatus and processes controllably permit the adjustment and selection of key bubble parameters through bubble generation actuation and orientation techniques and through selection of bubble fluid compositions in order to facilitate medical research and/or to optimize treatment for imaging, therapy, sonoporation, inertial and non-inertial cavitation, and acoustic activation, among other medical uses. Disposable cartridges containing such bubbles are provided and may include means for patient infusion.

1 . A medical bubble generator device producing medically useful bubbles of medically desirable size, size distribution, concentration and homogeneity, comprising:
 a base station;   a cradle rotatably mounted to the base station;   a disposable cartridge removably mounted to the cradle;   said cradle including first and second fluid delivery means mounted for rotation with said cradle;   said cartridge including first and second fluid vessels and a bubble generating module intermediate said first and second fluid vessels that are connected along a flow path; and   said cradle adapted to selectively orient the removable cartridge and said first and second fluid delivery means adapted to controllably move fluid through the first and second fluid vessels of the removable carriage when it is in a selected orientation so as to produce said medically useful bubbles of medically desirable size, size distribution, concentration and homogeneity in said removable, disposable cartridge.   
     
     
         2 . The invention of  claim 1 , wherein said first and second fluid delivery means are first and second linear actuators. 
     
     
         3 . The invention of  claim 2 , wherein said cradle is manually adapted to selectively orient the removable cartridge and said actuators are manually adapted to controllable move fluid through the removable cartridge when in a selected orientation so as to produce said medically useful bubbles of medically desirable size, size distribution, concentration and homogeneity in said removable, disposable cartridge. 
     
     
         4 . The invention of  claim 2 , wherein said cradle is adapted to selectively orient the removable cartridge in response to a programmable controller and said actuators are adapted to controllable move fluid through the removable cartridge when in a selected orientation in response to said programmable controller so as to produce said medically useful bubbles of medically desirable size, size distribution, concentration and homogeneity in said removable, disposable cartridge. 
     
     
         5 . The invention of  claim 2 , wherein at least one of said rotatable cradle and linear actuators are operated to provide at least one cycle of reciprocating flow such that each cycle fluid is caused first to flow in one direction along said flow path out of one and into the other one of the fluid vessels via the bubble generating module of said removable, disposable cartridge and then caused to flow along said flow path of said removable, disposable cartridge in a second direction counter to and opposing said first direction out of the other one and into the first one of the fluid vessels via the bubble generating module in such a way that first the one and then the other of the first and second fluid vessels of the removable, disposable cartridge is vertically oriented when fluid is caused to flow in the first and second directions. 
     
     
         6 . The invention of  claim 5 , wherein said first and second fluid vessels and intermediate bubble generating module are in-line first and second fluid vessels and intermediate bubble generating module. 
     
     
         7 . The invention of  claim 6 , wherein said rotatable cradle is operated to invert the removable, disposable cartridge each half cycle of a reciprocal cycle. 
     
     
         8 . The invention of  claim 6 , wherein said bubble generating module of said in-line first and second fluid vessels and intermediate bubble generating module consists of a single, capillary tube and a single mix chamber in spaced apart relation to said capillary tube. 
     
     
         9 . The invention of  claim 2 , wherein at least one of said linear actuators is operated to so move fluid along said flow path of said removable, disposable cartridge as to purge unwanted components including foam and undesirably large bubbles from said medically useful bubbles of medically desirable size produced in said removable, disposable cartridge. 
     
     
         10 . The invention of  claim 2 , wherein for an initial reciprocal cycle at least one of the cradle and linear actuators are operated to reciprocally move fluid along said flow path of the removable, disposable cartridge in the first and second directions at first and second comparatively high and comparatively low speeds to avoid damaging sensitive fluid components, the comparatively low speed set by a speed threshold beyond which sensitive fluid components may be damaged, and are operated for at least one additional reciprocal half cycle to move fluid along said flow path of the removable, disposable cartridge in at least one the first and second directions at speeds below the speed threshold for damaging sensitive fluid components to produce said medically useful bubbles of medically desirable size, size distribution, concentration and homogeneity. 
     
     
         11 . The invention of  claim 9 , wherein said cradle is operated to so rotate said removable cartridge as to increase the concentration of said bubbles produced therein by a centrifuge action and wherein at least one of said linear actuators is operated to purge unwanted components from said increased concentration bubbles. 
     
     
         12 . The invention of  claim 9 , wherein, in addition to said medically useful bubbles, unwanted components are contained in said removable cartridge, and wherein said cradle is operated to so rotate said cartridge as to separate the unwanted components from said medically useful bubbles by a centrifuge action. 
     
     
         13 . The invention of  claim 12 , wherein said unwanted components include an unbound drug. 
     
     
         14 . The invention of  claim 1 , wherein said first and second fluid vessels are comparatively expensive and comparatively inexpensive first and second comparatively high and comparatively low burst pressure syringes. 
     
     
         15 . The invention of  claim 2 , wherein said at least one cycle of reciprocating flow along said flow path is accomplished at a predetermined, comparatively high speed, wherein the first and second fluid vessels have a bore size, wherein said linear actuators have a maximum speed, and wherein a combination of actuator speed and bore size is selected such that comparatively larger bore sizes are selectively combined with comparatively slower linear actuator speeds to provide said predetermined, comparatively high speed.