Cell substrate electrical impedance sensor with multiple electrode array

An apparatus for monitoring cell-substrate impedance, comprising:

• means defining a plurality of separate tissue culture chambers in a matrix, each tissue culture chamber having a solid growth surface on which a tissue culture containing a multiplicity of cells may grow, the cells having ventral surfaces at least partly in contact with the growth surface;
• a measuring electrode directly on each growth surface, each measuring electrode having an area of less than 10.sup.-2 cm.sup.2 so that the ventral surfaces of from 1 to about 50 cells are at least partly in contact with the measuring electrode;
• means for measuring impedance of the cells in at least partial contact with the measuring electrode, connected to the measuring electrode of each tissue culture chamber, said means for measuring impedance including a reference electrode in each tissue culture chamber which has an area that is greater than the area of the measuring electrode, an upper substrate (14) having a first electrode layer (16) thereon, the upper substrate having a plurality of first holes (20) therethrough which extend through the first electrode layer, each first hole being in one of the tissue culture chambers;
• a plurality of well walls (12) engaged on the upper substrate around respective first holes and around at least a portion of the first electrode layer to define the reference electrodes (18) around at least a portion of each first hole, the plurality of well walls comprising the means defining the plurality of separate tissue culture chambers;
• a lower substrate (22) engaged under the upper substrate, the lower substrate having a second electrode layer (24) thereon extending between the upper and lower substrates and under at least a portion of each first hole;
• an insulation layer (26) between the upper substrate and the second electrode layer extending at least under each first hole, the insulation layer having a plurality of second holes (28) therethrough and in each respective first hole for exposing areas of the second electrode layer to define the measuring electrodes (30) in the first hole;
• the means for measuring impedance including electric power means (46) connected between the measuring and reference electrodes for applying electric power between the electrodes, and electric impedance monitoring means (48) connected between said measuring and reference electrodes for monitoring electric impedance between the electrodes.