Needle array assembly and method for delivering therapeutic agents

Abstract

A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality, of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

What is claimed is: 
     
         1 .- 103 . (canceled) 
     
     
         104 . A method of evaluating one or more candidate agents comprising:
 i) introducing said one or more candidate agents to one or more positions in a tissue in vivo, and   ii) evaluating an effect of said one or more candidate agents on said tissue,   wherein each of said one or more candidate agents is in a pharmaceutical composition, and   wherein at least one of said one or more pharmaceutical compositions comprises an indicator particle.   
     
     
         105 . The method of  claim 104 , wherein said tissue is a solid tumor. 
     
     
         106 . The method of  claim 104 , wherein said indicator particle is selected from a metallic particle, a fluorescent dye, a quantum dot, a quantum barcode, a radiographic contrast agent, and a magnetic resonance imaging contrast agent. 
     
     
         107 . The method of  claim 106 , wherein said indicator particle is a fluorescent dye. 
     
     
         108 . The method of  claim 104 , wherein at least one of said candidate agents is a positive control or a negative control. 
     
     
         109 . The method of  claim 104 , wherein said introducing in (i) is performed using a device comprising one or more needles. 
     
     
         110 . The method of  claim 109 , wherein said needles are arranged in an array. 
     
     
         111 . The method of  claim 109 , wherein said one or more needles are configured for passive delivery of said one or more candidate agents. 
     
     
         112 . The method of  claim 109 , wherein said device comprises needles with micropits over their surfaces. 
     
     
         113 . The method of  claim 109 , wherein said device comprises needles made from porous material. 
     
     
         114 . The method of  claim 109 , wherein at least one of said one or more needles is charged with a candidate agent by immersion in said candidate agent. 
     
     
         115 . The method of  claim 109 , wherein each of said one or more needles is configured to deliver said one or more candidate agents to spatially defined locations along parallel axes in said solid tumor. 
     
     
         116 . The method of  claim 109 , wherein each of said one or more needles is configured to deliver said one or more agents in a column-shaped region coaxial with respect to a delivery axis. 
     
     
         117 . The method of  claim 109 , wherein each of said one or more needles comprises a plurality of ports. 
     
     
         118 . The method of  claim 117 , wherein said plurality of ports are sized and positioned to deliver a substantially equal amount of fluid. 
     
     
         119 . The method of  claim 104 , wherein said introducing in (i) comprises delivering less than 1 μL of one or more candidate agents per needle to said solid tumor. 
     
     
         120 . The method of  claim 109 , wherein said one or more needles are close-ended. 
     
     
         121 . The method of  claim 106 , wherein said introducing in (i) comprises delivering, with said device, a plurality of different agents to a plurality of different positions within said solid tumor. 
     
     
         122 . The method of  claim 104 , wherein each of said one or more candidate agents is introduced in an amount that is less than a minimal dose required to produce a detectable effect in an adult or in an amount that is undetectable outside said solid tumor. 
     
     
         123 . The method of  claim 104 , further comprising introducing one or more indicators of efficacy into said solid tumor. 
     
     
         124 . The method of  claim 104 , wherein said evaluating in (ii) comprises detecting a degree of permeation of said one or more candidate agents through said solid tumor. 
     
     
         125 . The method of  claim 104 , wherein said evaluating in (ii) comprises assessing efficacy, activity or toxicity of said one or more candidate agents on said solid tumor. 
     
     
         126 . The method of  claim 104 , wherein at least one of said candidate agents is a chemotherapeutic. 
     
     
         127 . The method of  claim 104 , wherein at least one of said candidate agents is a preclinical or clinical drug.