Microwell design and fabrication for generation of cell culture aggregates

Abstract

A cell culture apparatus may include a substrate defining a well. The well may define an interior surface, an exterior surface, an upper aperture and a nadir. The substrate may define a thickness between the interior and exterior surfaces that has a thickness proximate the nadir that is greater than or equal to a thickness proximate the upper aperture.

What is claimed is: 
     
         1 . A cell culture apparatus comprising:
 a substrate defining a well, wherein the well defines an interior surface having a hemispheric shape, an exterior surface, an upper aperture and a nadir;   wherein the substrate defines a thickness between the interior surface and the exterior surface;   wherein the thickness increases continuously from proximate the upper aperture to the nadir.   
     
     
         2 . The cell culture apparatus of  claim 1 , wherein the thickness of the substrate proximate to the nadir is greater than the thickness of the substrate proximate to the upper aperture. 
     
     
         3 . The cell culture apparatus of  claim 1 , wherein the well defines an axis between the nadir and a center of the upper aperture, wherein the well is rotationally symmetrical about the axis. 
     
     
         4 . The cell culture apparatus according to  claim 1 , wherein the upper aperture defines a distances across the upper aperture, wherein the distance across the upper aperture is in a range from 100 micrometers to 3000 micrometers. 
     
     
         5 . The cell culture apparatus according to  claim 1 , wherein the thickness of the substrate at any location from proximate the upper aperture to the nadir is in a range from 10 micrometers to 1000 micrometers. 
     
     
         6 . The cell culture apparatus of  claim 1 , wherein interior surface is defined by a hemispherical shape, wherein the hemispherical shape defines a radius in a range from 50 micrometers to 1500 micrometers. 
     
     
         7 . The cell culture apparatus according to  claim 1 , wherein the substrate comprises polystyrene. 
     
     
         8 . The cell culture apparatus according  claim 1 , wherein exterior surface is configured to transmit light substantially parallel to a direction that the light was received by the interior surface when the well contains a cell culture medium. 
     
     
         9 . The cell culture apparatus according to  claim 1 , wherein a shape of the interior surface and a shape of the exterior surface are configured to minimize refraction of light that passes there between when the well contains a cell culture medium. 
     
     
         10 . The cell culture apparatus according to  claim 1 , wherein the well is non-adherent to cells. 
     
     
         11 . The cell culture apparatus according to  claim 1 , wherein the interior surface is configured such that cells cultured therein form a spheroid. 
     
     
         12 . A cell culture apparatus comprising:
 a reservoir comprising a bottom and an enclosing sidewall, wherein the bottom is defined by a plurality of wells, wherein each well of the plurality of wells defines an interior surface, an exterior surface, an upper aperture and a nadir, wherein each well defines a thickness between the interior surface and the exterior surface, wherein the thickness increases continuously from proximate the upper aperture to the nadir.   
     
     
         13 . The cell culture apparatus of  claim 12  wherein the thickness is configured to correct for refraction of light passing into the interior surface and out of the exterior surface when the well contains a water-based composition. 
     
     
         14 . The cell culture apparatus of  claim 12  wherein a shape of the exterior surface is configured to correct for refraction of light passing into the interior surface and out of the exterior surface. 
     
     
         15 . The apparatus of  claim 1 , wherein said exterior surface has an aspheric exterior surface. 
     
     
         16 . Use of the apparatus of  claim 1  for the growth of a spheroid. 
     
     
         17 . Use of the apparatus of  claim 12  for the imaging of a cell in said well. 
     
     
         18 . The use of  claim 17 , wherein said cell is in a spheroid.