Devices and methods for measurement of liquid volumes

Abstract

Methods and devices for measuring the volume of a liquid sample transferred from a source to a destination by means of incremental dispensing of the sample into a destination vessel or by means of decremental aspiration of the sample from a source vessel, where the liquid sample is collected from a liquid having known optical absorbance at a known wavelength or within a defined part of the electromagnetic spectrum. The absorbance of the sample is measured by exposing the source or destination vessel to electromagnetic radiation before and after the transfer, and the liquid volume is determined on the basis of differential measurements of absorbance of the source or destination vessel.

What is claimed is: 
     
         1 . A method for measuring the volume of a liquid sample having known optical absorbance at a defined wavelength or within a defined portion of the electromagnetic spectrum comprising:
 a. transferring from a source to a destination vessel a liquid sample by means of incremental dispensing of the sample into a destination vessel or by means of decremental aspiration of the sample from a source vessel;   b. measuring the absorbance of the sample by exposing the source or destination vessel to electromagnetic radiation before and after the transfer; and   c. determining the liquid volume transfer performances on the basis of differential measurements of absorbance of the source or destination vessel.   
     
     
         2 . A method for the determination of the volume of a liquid sample having known optical absorbance at a defined wavelength or within a defined portion of the electromagnetic spectrum comprising:
 a. performing a first absorbance measurement of a second sample with different or identical absorbance properties into a destination vessel, wherein the light path crosses an unconstrained liquid surface in contact with gas;   b. dispensing the first sample into the same destination vessel; and   c. performing a second absorbance measurement in the destination vessel of the sample mixture to determine the total absorbance at the defined wavelength or within a defined portion of the electromagnetic spectrum, wherein the light path crosses an unconstrained liquid surface in contact with gas, wherein the method allows minimizing the dependence of the liquid volume determination calculation from the meniscus shape of the second sample and sample mixture.   
     
     
         3 . A method for determination of the liquid volume of a sample having known light absorbing properties comprising:
 a. dispensing a first volume of a second sample with identical or different absorbing properties;   b. performing a first measurement of the absorbing properties of the second sample;   c. dispensing the sample for measurement;   d. performing a second measurement of the absorbing properties of the sample mixture inside a vessel; and   e. determining the liquid volume of first sample by means of the differential analysis of the first and second absorbance measurement, wherein the first volume of said second sample is adjusted to deliver a desired absorbance of the liquid mixture that minimizes the systematic or random error from the reader.   
     
     
         4 . A method for the determination of the liquid volume of a multiplicity of samples from a solution with defined absorbance properties comprising:
 a. transferring a first multiplicity of samples to a corresponding multiplicity of vessels;   b. performing a first measurement of the absorbance of the sample-containing vessels;   c. transferring a second multiplicity of samples to a corresponding multiplicity of vessels;   d. performing a second measurement of the absorbance of the sample-containing vessels;   e. extracting the absorption properties of the vessels from the first absorbance measurement; and   f. reconstructing the individual liquid volumes of the second multiplicity of samples through subtraction of the vessel absorbance properties from the second measurement of absorbance.   
     
     
         5 . The method of  claim 4 , wherein the multiplicity of vessels are part of a multi-well consumable. 
     
     
         6 . A method for the determination of the liquid volume of a sample that exceeds the maximum capacity of one destination vessel, comprising:
 a. splitting exhaustively the sample in a multiplicity of aliquots of unknown volume;   b. dispensing the same aliquots in a multiplicity of destination vessels;   c. measuring the absorbance of those aliquots through other methods; and   d. reconstructing the original liquid volume of the sample through analysis of the individually measured absorbance.   
     
     
         7 . A method for measuring the liquid volume of a sample comprising:
 a. measuring the absorbance of the destination vessel;   b. dispensing a sample to the destination vessel;   c. measuring a second time the absorbance of the destination vessel;   d. aspirating the sample from the destination vessel;   e. measuring a third time the absorbance of the destination vessel; and   f. determining the liquid volume transfer from the series of absorbance measurements available.   
     
     
         8 . A method to determine the amount of liquid volume lost during the transfer of sample with defined absorbance properties comprising:
 a. performing an absorbance measurement on the source and destination vessel;   b. transferring a liquid volume from the source to the destination vessel;   c. performing a second absorbance measurement on the source and destination vessel; and   d. quantifying the liquid volume losses from the analysis of the source variation of absorbance against the destination variation of absorbance.   
     
     
         9 . A method for the determination of the liquid volume of a sample with defined optical absorbance properties, comprising:
 a. inserting a certain liquid volume of sample into a vessel;   b. adding, before or after the sample, a suitable amount of light absorbing or non-absorbing liquid;   c. measuring the absorbance of the sample mixture in a configuration where the light path crosses an unconstrained liquid surface in contact with gas; and   d. reconstructing the liquid volume on the basis of the total absorbance of the mixture, wherein the suitable volume of light absorbing or non-absorbing liquid is chosen with the purpose of having a substantially constant path-length measurement substantially independent of the sample volume.   
     
     
         10 . A device for the storage of liquid samples comprising:
 a. an hermetically sealed container containing the sample;   b. a pierceable portion, designed to be perforated by the tip or nozzle of a liquid delivery device; and   c. wherein the action of aspirating the liquid volume perforates the pierceable portion in an irreversible manner and allows accessing the liquid.   
     
     
         11 . The device of  claim 10 , wherein the sealed container is a blister pack and the pierceable portion is its cover. 
     
     
         12 . The device of  claim 10 , wherein the sealed container is a blister pack and the pierceable portion is its cover. 
     
     
         13 . The device of  claim 10 , wherein the liquid sample have defined absorption properties for the purpose of liquid handling volumes determination. 
     
     
         14 . The device of  claim 11 , wherein the cover comprises peelable film to prevent possible contamination of the tip from the outer surface of the cover when it's pierced by the liquid delivery device. 
     
     
         15 . A device for the storage of liquid samples comprising;
 a. a liquid container;   b. a specifically designed structure above the surface of the liquid; and   c. wherein the specifically designed structure cleans the outer surface of the tip or nozzle of a liquid delivery device following aspiration of the liquid.   
     
     
         16 . The device of  claim 15 , wherein the specifically structure comprises a film, or a fibrous septum, or a sponge material, or a metallic mesh. 
     
     
         17 . The device of  claim 15 , wherein the container is a blister pack or a microplate and the specifically designed structure is a film integrated in the cover. 
     
     
         18 . A device for the storage of liquid samples used for the purpose of liquid volume determination, comprising optical or magnetic or electronic machine-readable markers that contain direct or indirect information about the specific sample solution absorbance. 
     
     
         19 . The device of  claim 10 , wherein the integrity of the pierceable portion is determined by means of image acquisition and processing methods, through visual image identification of a possible aperture in the pierceable portion created by the tip or the nozzle of the liquid delivery device. 
     
     
         20 . The device of  claim 10 , wherein the integrity of the pierceable portion is determined by positive or negative recognition of optical markers suitably located on the pierceable portion as an irreversible consequence of the piercing action of the tip or nozzle of the liquid delivery device. 
     
     
         21 . A method for the determination of the volume of a liquid sample having known optical absorbance at a defined wavelength or within a defined portion of the electromagnetic spectrum, wherein the liquid sample is composed by a light absorbing dye with high molecular weight and by a light transparent buffer to minimize the negative effects of evaporation during the method execution following the liquid sample aspiration. 
     
     
         22 . A method for measuring the volumetric performances of a liquid handling device comprising:
 a. aspirating from a source vessel a colloid using the liquid handling device;   b. optionally dispensing the colloid into a destination vessel;   c. measuring the absorbance of the colloid by exposing the source or destination vessel to electromagnetic radiation before and after the aspiration or dispensing; and   d. determining the volumetric performances of the liquid handling device on the basis of the absorbance of the colloid.   
     
     
         23 . An apparatus for measuring the volumetric performances of a liquid handling device comprising:
 a. a liquid handling device;   b. at least one source vessel containing a colloid; and   c. an optional destination vessel, wherein the volumetric performances of the liquid handling device are measured from the absorbance of the colloid determined by exposing the source or destination vessel to electromagnetic radiation before and after the transfer.   
     
     
         24 . A method for measuring the volume of a liquid sample having known optical absorbance at a defined wavelength  6   r  within a defined portion of the electromagnetic spectrum comprising:
 a. aspirating from a source vessel a liquid sample;   b. measuring the absorbance of the source vessel sample by means of electromagnetic radiation before and after the aspiration; and   
       determining the liquid volume transfer performances on the basis of differential measurements of absorbance of the source vessel.