Gentle, Automated Media Exchange for 3D Spheroid Cultures in 384- and 96-Well Plates

Jonas Schoendube1, Frank Schwemmer1
1ADDIMUS BIO, Freiburg, Germany

Abstract

  • Problem: Media exchange for 3D spheroid culture is a major automation bottleneck due to tissue loss with conventional aspiration and limited scalability.
  • Solution: Automated workflow for 384- and 96-well U-bottom plates using optimized nozzle geometry and low-shear fluidics.
  • Result: Zero tissue loss after five wash cycles; 80% volume exchange; 20 plates processed hands-off in 1–1.5 hours.

Approach

  • Custom washing cassettes on INTEGRA WELLJET with eight nozzles and passive valving.
  • Gentle aspiration of used medium; fresh medium dispensed through bent steel nozzles against well wall to minimize flow across spheroids.
  • Cell Culture: MCF7 in DMEM (+10% FBS, 1% Pen/Strep); Akita PrimeSurface 384 and Thermo Nunclon Sphera 96 U-bottom plates; 5 cells/µL; 70 µL (384) / 200 µL (96) dispensed volumes.

Results

  • 80% volume exchange (55 µL aspirated from 70 µL in 384; 145 µL from 200 µL in 96).
  • Zero tissue loss confirmed by microscopy after five wash cycles.
  • Processing: < 2.5 min (96-well), < 5 min (384-well).
  • > 20 plates can be stacked and processed without operator intervention.
  • Washing tested for Matrigel domes in flat-bottom wells; HTS-compatible.

Joint system for media exchange comprising:
INTEGRA WELLJET and ADDIMUS washing cassette

Fig. 1: Integra's WELLJET Dispenser Stacker

Fig. 2: ADDIMUS's WASH+ cassette incl. passive valving

Wash Principle and Sample Results

Fig. 3: Schematic of washing

Fig. 4: (Left) 96-well-plate before exchange of medium;
(Right) 96-well-plate after exchange of medium

See the workflow in action
View Demonstration
0%Tissue loss
15 µLResidual volume
10+384-well plates/hour
Supported by:EXISTuniversität freiburg