Cooled Dispensing of µL-Scale Matrigel Domes using off-the-shelf Bulk Dispensers

Abstract

  • Matrigel is an essential reagent in 3D cell culture and needs to be handled below 10 C to prevent gelation.
  • Off-the-shelf bulk dispensers such as the MultiDrop Combi do not support cooled dispensing.
  • Conventionally, researchers pre-cool the dispensing cassette with ice-cold PBS, but this still results in dispensed sample temperatures above 15 C.
  • We present a simple cooling solution for bulk dispensers that cools the sample below 10 C and enables filling more than 10 plates.

Approach

  • 10x reduced dead volume, down to about 100 µL, through a novel dispensing cassette design.
  • Passive pump cooling with phase change material and a custom designed aluminum casing.
  • Passive reservoir cooling with phase change material.
  • Single-use reservoirs mountable directly on the cassette for a compact cooled dispensing workflow.

Results

  • Cooled sample can be dispensed below 10 C for more than 10 384-well plates.
  • 4 µL domes can be robustly placed in 96-well plates.
  • 7 µL is sufficient to cover the bottoms of 384-well plates.
  • Cell viability has been confirmed by culturing MCF7 breast cancer cells after dispensing.

Cooling setup and elongated nozzle geometry

Fig. 1: Passive pump cooler and reservoir cooler mounted on dispenser

Fig. 2: Elongated dispensing nozzles allow accurate dome placement

Reservoir and cassette architecture for cooled low-volume dispensing

Fig. 3: a) Different reservoir and cooler sizes; b) low dead volume cassette with elongated dispensing needles

Dome placement and thermal performance during dispensing

Fig. 4: a) Matrigel dispensed in 384-well plate; b) 4 µL Matrigel domes in 96-well plate; c) temperature of the dispensed liquid with or without cooler

Cell culture compatibility and confluency after dispensing

Fig. 5: Cell culture images and confluency over time

<10 Cfor >10 plates
<100 µLdead volume
10 plateswith <3 ml sample
Supported by:EXISTuniversitat freiburg