Precise nanoliter fluid handling system with integrated high-speed flow sensor.

A system for accurate low-volume delivery of liquids in the micro- to nanoliter range makes use of an integrated miniature flow sensor as part of an intelligent feedback control loop driving a micro-solenoid valve. The flow sensor is hydraulically connected with the pressurized system liquid in the dispensing channel and located downstream from the pressure source, above the solenoid valve. The sensor operates in a differential mode and responds in real-time to the internal flow-pulse resulting from the brief opening interval of the solenoid valve leading to a rapid ejection of a fluid droplet. The integral of the flow-pulse delivered by the sensor is directly proportional to the volume of the ejected droplet from the nozzle. The quantitative information is utilized to provide active control of the effectively dispensed or aspirated volume by adjusting the solenoid valve accordingly. This process significantly enhances the precision of the fluid delivery. The system furthermore compensates automatically for any changes in the viscosity of the dispensed liquid. The data delivered by the flow sensor can be saved and backtracked in order to confirm and validate the aspiration and dispensing process in its entirety. The collected dispense information can be used for quality control assessments and automatically be made part of an electronic record.

[1]  R. Houghten General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Richard Ellson Picoliter: enabling precise transfer of nanoliter and picoliter volumes , 2002 .

[3]  Curtis Weibel “The Spotting Accelerator™”, Customizable Head Assembly for Advanced Microarraying , 2002 .

[4]  Matthew Cook,et al.  Mosquito®: An Accurate Nanoliter Dispensing Technology , 2004 .

[5]  J G Houston,et al.  The chemical-biological interface: developments in automated and miniaturised screening technology. , 1997, Current opinion in biotechnology.

[6]  S. Ekström,et al.  Microdispensing and Nanovial Arrays Provides Rapid Automated Protein/Peptide Identification using MALDI-TOF MS: , 2000 .

[7]  Richard N. Ellson,et al.  Transfer of low nanoliter volumes between microplates using focused acoustics-automation considerations , 2003 .

[8]  Joerg Schlegel Flexible, Parameter-Controlled Nanoliter Pipetting on a Tecan xyz Platform , 2000 .

[9]  Matthias G. O. Lorenz,et al.  Liquid-Handling Robotic Workstations for Functional Genomics , 2004 .

[10]  Mitchel J. Doktycz,et al.  Hybrid Valve Structure for High-Throughput, Low-Volume Liquid-Handling Applications , 2004 .

[11]  James E. Stanchfield,et al.  Submicroliter Liquid Handling 384 Wells at a Time , 1999 .

[12]  Steven D. Hamilton,et al.  HTS Automation Study: Results from a 2001 Survey of the Current vs. Desired State of HTS Automation , 2002 .

[13]  Dean Billheimer,et al.  Integrating histology and imaging mass spectrometry. , 2004, Analytical chemistry.

[14]  A. Lemmo,et al.  Micro parallel liquid chromatography: enabling technology for discovery analytical chemistry. , 2004, Assay and drug development technologies.

[15]  Mike Jones,et al.  The Importance of the Quality Control of Laboratory Automation , 2003 .

[16]  Bart van der Schoot,et al.  High-Speed Flow Sensing as a Diagnostic Tool in the Development of Microfluidic Systems , 2000 .

[17]  N. D. Rooij,et al.  Two-Dimensional Parallel Dispenser for Microarray Printing: , 2003 .

[18]  Alexander Shvets,et al.  Spot-on™ Technology for Low Volume Liquid Handling , 2002 .

[19]  P. Fortina,et al.  System for preparing microhybridization arrays on glass slides. , 1998, Analytical chemistry.

[20]  J. W. Parce,et al.  Electrokinetically controlled microfluidic analysis systems. , 2000, Annual review of biophysics and biomolecular structure.

[21]  T Laurell,et al.  Picoliter sample preparation in MALDI-TOF MS using a micromachined silicon flow-through dispenser. , 1998, Analytical chemistry.

[22]  Donald J. Rose,et al.  Characterization of an inkjet chemical microdispenser for combinatorial library synthesis , 1997 .