Fast calibration of a dispenser nozzle for delivery of microdroplets over a flexible substrate

In this work we present a method for delivering small fluid volumes possibly containing cells and particles over a flexible large area substrate. Particles are deposited by a dispensing device that performs serial delivery of liquid volumes in the range of 200 pL. Due to the required precision, the alignment and the calibration of the spotting system are crucial for the proper performance of the delivery process. The system provides automated motion of mechanical parts with micrometric precision. To address the problem of the device deformation caused by the flexibility of the substrate, the 3D coordinates of each site need to be known, but the serial acquisition of all the coordinates would be highly time consuming for high-throughput arrays and large devices. We solved this problem by sampling the coordinates of a small subset and interpolating the positions of the remaining sites by means of a custom algorithm. System calibration for a device with 1536 sites was achieved in 150 s vs. 9630 s required for full sampling. Measurements performed with fluorescent microbeads showed that 100% of the particles were deposited within a spot with a radius of 50 μm.