Plate and method for high throughput screening

Abstract

A multiple well plate and method for media exchange, including a body defining a plurality of cell wells each connected via a channel to one of a plurality of aspiration holes, is provided. The cell wells contain a porous, hydrophilic frit which is suspended on a ledge above a reservoir of fluid media and supports a tissue sample. The properties of the frit wick the fluid media upwards to supply the tissue sample with nutrients for growth and proliferation. Old media is aspirated from the wells by a liquid handling device which inserts a pipette tip into the aspiration holes. The pipette tip applies a suction pressure which draws the media out of the cell well, through the channel, into the aspiration hole and out through the pipette tip. New media is dispersed through the pipette tip and directly into the cell well.

1 . An apparatus for automated, high throughput screening of tissue, said apparatus comprising: 
 at least one media supply tip connected in fluid communication with a media supply;    at least one aspiration tip connected in fluid communication with a vacuum pressure supply;    a seal embracing the aspiration tip;    a robotic manipulator capable of articulating said tips through a range of motion; and    at least one plate positioned within the range of motion of the tips articulated by the robotic manipulator and including a body having an upper surface, said body defining: 
 a first hole having a first hole upper edge defined by the upper surface of the body and a first hole bottom portion defined within the body and below the upper surface of the body, said first hole being configured to receive the tissue and the media supplied through the media supply tip and to hold the media so as to bathe the tissue; and  
 a second hole having a second hole upper edge defined by the upper surface of the body and a second hole bottom portion defined within the body and below the upper surface of the body, the second hole bottom portion being connected in fluid communication with the first hole bottom portion, said second hole being configured to receive the aspiration tip so that said seal embracing the aspiration tip abuts the upper surface surrounding the upper edge and seals against application of the vacuum pressure to aspirate media from the first hole through the aspiration tip.  
   
     
     
         2 . An apparatus of  claim 1 , wherein the seal defines a passage therethrough allowing the seal to encircle the aspiration tip.  
     
     
         3 . An apparatus of  claim 2 , wherein the passage has a diameter of at most 90% a maximum diameter of the aspiration tip.  
     
     
         4 . An apparatus of  claim 2 , wherein the seal has a frustoconical shaped end with the passage extending axially therethrough.  
     
     
         5 . An apparatus of  claim 4 , wherein the frustoconical shaped end has an angle of 70 degrees.  
     
     
         6 . An apparatus of  claim 1 , further comprising a collar secured around the tip adjacent the seal.  
     
     
         7 . An apparatus of  claim 6 , wherein the collar includes a steel bushing with an opening therethrough sized to receive the tip.  
     
     
         8 . An apparatus of  claim 6 , wherein the collar further includes a set screw configured to trap the tip by abutting the tip in a friction fit.  
     
     
         9 . An apparatus of  claim 1 , wherein the seal is constructed of a silicone material.  
     
     
         10 . An apparatus of  claim 1 , wherein the aspiration tip is further connected in fluid communication to an anti-microbial liquid supply.  
     
     
         11 . An apparatus of  claim 10 , further comprising a pump capable of pumping the anti-microbial liquid through the aspiration tip.  
     
     
         12 . An apparatus of  claim 10 , wherein the anti-microbial liquid includes ethanol.