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

Abstract 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.

[1]  N. Manaresi,et al.  A CMOS chip for individual cell manipulation and detection , 2003, 2003 IEEE International Solid-State Circuits Conference, 2003. Digest of Technical Papers. ISSCC..

[2]  Roberto Guerrieri,et al.  The biocompatibility of materials used in printed circuit board technologies with respect to primary neuronal and K562 cells. , 2010, Biomaterials.

[3]  B. Derby,et al.  Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing. , 2008, Biomaterials.

[4]  Roberto Guerrieri,et al.  A lab-on-a-chip for cell detection and manipulation , 2003 .

[5]  E. Delamarche,et al.  Microfluidics for Processing Surfaces and Miniaturizing Biological Assays , 2005 .

[6]  Roland Zengerle,et al.  The dispensing well plate: a novel nanodispenser for the multiparallel delivery of liquids (DWP Part I) , 2004 .

[7]  Roberto Guerrieri,et al.  Horizontal nDEP cages within open microwell arrays for precise positioning of cells and particles. , 2010, Lab on a chip.

[8]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[9]  Martin D. Buhmann,et al.  Radial Basis Functions , 2021, Encyclopedia of Mathematical Geosciences.

[10]  Richard K. Beatson,et al.  Surface interpolation with radial basis functions for medical imaging , 1997, IEEE Transactions on Medical Imaging.

[11]  R. Zengerle,et al.  A tunable and highly-parallel picoliter-dispenser based on direct liquid displacement , 2002, Technical Digest. MEMS 2002 IEEE International Conference. Fifteenth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.02CH37266).

[12]  Tuan Vo-Dinh,et al.  Microarray sampling-platform fabrication using bubble-jet technology for a biochip system , 2001, Fresenius' journal of analytical chemistry.

[13]  R Guerrieri,et al.  Dielectrophoretic trapping in microwells for manipulation of single cells and small aggregates of particles. , 2009, Biosensors & bioelectronics.

[14]  Bradley J Nelson,et al.  Autofocusing in computer microscopy: Selecting the optimal focus algorithm , 2004, Microscopy research and technique.

[15]  R. Guerrieri,et al.  Electronic Microsystems for Handling of Rare Cells , 2010, IEEE Transactions on Electron Devices.

[16]  Christophe Chanel,et al.  Autofocus for automated microassembly under a microscope , 1996, Proceedings of 3rd IEEE International Conference on Image Processing.

[17]  Jing Cheng,et al.  A microchip-based PCR device using flexible printed circuit technology , 2005 .

[18]  Z Hugh Fan,et al.  Macro-to-micro interfaces for microfluidic devices. , 2004, Lab on a chip.

[19]  Brian Derby,et al.  Ink-jet delivery of particle suspensions by piezoelectric droplet ejectors , 2005 .