Apparatus and methods for parallel processing of micro-volume liquid reactions

A method for adding a component to a micro-volume reaction, wherein the method comprises the steps of:

• (a) providing a first apparatus comprising a first sample chamber containing a reaction mixture;
• (b) providing a second apparatus comprising a second sample chamber containing the component;
• and
• (c) bringing the apparatuses into proximity such that liquid contact is established between the first sample chamber and the second sample chamber;
• wherein each apparatus comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is in the form of a thin film such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• wherein the sample chamber has a height to width ratio of less than 1:1, wherein the height of the sample chamber is measured from one face of the substrate to the other.

A method for adding a nucleic acid to a micro-volume reaction, wherein the method comprises the steps of:

• (a) providing a first apparatus comprising a first sample chamber containing a reaction mixture;
• (b) providing a second apparatus comprising a second sample chamber containing the nucleic acid;
• and
• (c) bringing the apparatuses into proximity such that liquid contact is established between the first sample chamber and the second sample chamber;
• wherein each apparatus comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber.

A method for introducing a liquid sample into a sample chamber, wherein the method comprises the steps of:

• (a) contacting an apparatus with a liquid solution;
• and
• (b) removing the apparatus from the solution;
• wherein the apparatus comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is in the form of a thin film such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• wherein the sample chamber has a height to width ratio of less than 1:1, wherein the height of the sample chamber is measured from one face of the substrate to the other.

A method for introducing a liquid sample comprising a nucleic acid into a sample chamber, wherein the method comprises the steps of:

• (a) contacting an apparatus with a liquid solution comprising a nucleic acid;
• and
• (b) removing the apparatus from the solution;
• wherein the apparatus comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber.

A method for diluting a solution, wherein the method comprises the steps of:

• (a) providing a first apparatus comprising a first sample chamber containing the solution
• (b) providing a second apparatus comprising a second sample chamber containing a diluent;
• and
• (c) bringing the apparatuses into proximity such that liquid contact is established between the first sample chamber and the second sample chamber;
• wherein each of the apparatuses comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is in the form of a thin film such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• wherein the sample chamber has a height to width ratio of less than 1:1, wherein the height of the sample chamber is measured from one face of the substrate to the other.

A method for diluting a solution comprising a nucleic acid, wherein the method comprises the steps of:

• (a) providing a first apparatus comprising a first sample chamber containing the solution which comprises a nucleic acid;
• (b) providing a second apparatus comprising a second sample chamber containing a diluent;
• and
• (c) bringing the apparatuses into proximity such that liquid contact is established between the first sample chamber and the second sample chamber;
• wherein each of the apparatuses comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber.

A method for selective retention of a molecule in a first sample chamber, wherein the method comprises the steps of:

• (a) providing a first apparatus, wherein the first sample chamber contains a solution comprising the molecule and one or more additional solute molecules of higher diffusibility;
• (b) providing a second apparatus comprising a second sample chamber containing a solvent;
• (c) bringing the apparatuses into proximity such that liquid contact is established between the first sample chamber and the second sample chamber;
• and
• (d) removing the apparatuses from proximity;
• wherein each of the apparatuses comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is in the form of a thin film such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• wherein the sample chamber has a height to width ratio of less than 1:1, wherein the height of the sample chamber is measured from one face of the substrate to the other.

A method for selective retention of a nucleic acid in a first sample chamber, wherein the method comprises the steps of:

• (a) providing a first apparatus, wherein the first sample chamber contains a solution comprising the nucleic acid and one or more additional solute molecules of higher diffusibility;
• (b) providing a second apparatus comprising a second sample chamber containing a solvent;
• (c) bringing the apparatuses into proximity such that liquid contact is established between the first sample chamber and the second sample chamber;
• and
• (d) removing the apparatuses from proximity;
• wherein each of the apparatuses comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber.

A method for parallel electrophoretic analysis of a plurality of micro-volume reactions, wherein the method comprises:

• (a) conducting the reactions in a microhole apparatus;
• (b) placing the apparatus in contact with an electrophoresis medium;
• and
• (c) conducting electrophoresis;
• wherein the apparatus comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber.

A method for preparing a plurality of samples for mass spectrometric analysis, wherein the samples are placed in an apparatus that comprises a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:

• (a) extends through the substrate;
• (b) comprises one or more walls and an opening at each end;
• and
• (c) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber.

A method for mixing a plurality of micro-volume samples, the method comprising:

• (a) providing a first microhole apparatus comprising a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• (b) providing a second microhole apparatus comprising a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:
• (i) extends through the substrate;
• (ii) comprises one or more walls and an opening at each end;
• and
• (iii) holds a sample such that the sample is retained in the apparatus through surface tension and such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• (c) bringing the apparatuses into proximity such that liquid contact is established between more than one sample chamber from the first apparatus and a sample chamber in the second apparatus.

An apparatus for containing multiple micro-volume liquid samples comprising a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:

• (a) extends through the substrate,
• (b) comprises one or more walls and an opening at each end, and
• (c) holds a sample such that the sample is in the form of a thin film such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• wherein the sample chamber has a height to width ratio of less than 1:1, wherein the height of the sample chamber is measured from one face of the substrate to the other.

A kit comprising an apparatus for containing multiple micro-volume liquid samples comprising a substrate, wherein the substrate defines a plurality of sample chambers, wherein each sample chamber:

• (a) extends through the substrate,
• (b) comprises one or more walls and an opening at each end, and
• (c) holds a sample such that the sample is in the form of a thin film such that a liquid sample present in one sample chamber does not intermix with a liquid sample present in another sample chamber;
• and
• wherein the sample chamber has a height to width ratio of less than 1:1, wherein the height of the sample chamber is measured from one face of the substrate to the other;
• and further comprising a reaction component packaged in a suitable container.