Method and apparatus for automated sample preparation
The present teachings provide apparatuses and methods for automated handling of samples, e.g., biological or chemical samples. The apparatuses and the methods of the present teachings allow automated performance of various sample manipulation steps without manual intervention. In a preferred embodiment, the present teachings provide apparatuses and methods for automated enrichment of templated beads produced by PCR.
1 . A method for preparing a biological sample for analysis, the method comprising:
forming a sample including a liquid portion and a bead complex, the bead complex comprising a first bead captured by a second bead, wherein the first bead carries amplified copies of a sample template nucleic acid, and wherein the second bead is a magnetic bead and carries an adapter sequence;
applying a magnetic field to the sample and thereby securing the bead complex within the magnetic field via magnetic attraction of the second bead to the magnetic field; and
processing the bead complex secured within the magnetic field to cause separating of the first bead from the second bead.
2 . The method of claim 1 , further comprising:
transferring, using an automated sample manipulation apparatus, the sample to a sample site configured to hold a volume of liquid, wherein the magnetic field is applied while the sample is held at the sample site.
3 . The method of claim 2 , wherein the sample site is located on a platform of the automated sample manipulation apparatus, the platform comprising a plurality of sample sites configured to respectively hold a plurality of volumes of liquid.
4 . The method of claim 3 , wherein the plurality of sample sites comprises a plurality of sample sites arranged in an array.
5 . The method of claim 2 , wherein the processing of the bead complex to cause separating of the first bead from the second bead comprises one or more of washing, mixing, heating, or stirring of the bead complex using the automated sample manipulation apparatus.
6 . The method of claim 2 , further comprising, before processing the bead complex, transferring, using the automated sample manipulation apparatus, one or more materials used in the processing to the bead complex, wherein the one or more materials are chosen from one or more of reagents, solutions, buffers, washes, and solvents.
7 . The method of claim 6 , wherein transferring the one or more materials includes transferring the one or more materials from at least one site preloaded with the one or more of the materials to the sample site at which the sample is held.
8 . The method of claim 7 , wherein the transferring the one or more materials from the at least one site preloaded with the one or more materials comprises aspirating the one or more materials from the at least one site preloaded with the one or more materials and dispensing the aspirated one or more materials at the sample site at which the sample is held.
9 . The method of claim 1 , wherein applying the magnetic field comprises applying an electromagnetic field.
10 . The method of claim 1 , wherein the magnetic field is a first magnetic field and the method further comprises:
after processing the bead complex and causing separating of the first bead from the second bead, applying a second magnetic field to secure the second bead within the second magnetic field; and
removing the first bead from the second magnetic field while the second bead is secured.
11 . The method of claim 10 , wherein the removing the first bead comprises using an automated sample manipulation apparatus to perform the removing.
12 . The method of claim 11 , further comprising:
after processing the bead complex and causing the separating of the first bead from the second bead, introducing a washing solution, using the automated sample manipulation apparatus, to wash the first and second bead; and
removing the second magnetic field using the automated sample manipulation apparatus.
13 . The method of claim 1 , wherein applying the magnetic field includes moving a magnet into position relative to a tube containing the sample such that the magnet provides the magnetic field within the tube.
14 . The method of claim 1 , wherein applying the magnetic field includes moving a tube containing the sample into position relative to a magnet such that the magnet provides the magnetic field within the tube.
15 . The method of claim 1 , wherein applying the magnetic field includes activating an electromagnet in a position relative to a tube including the sample such that electromagnet provides the magnetic field within the tube.
16 . The method of claim 1 ,
wherein the forming the sample comprises mixing a dispersion comprising the liquid portion, the first bead, and the second bead in a well to form the bead complex;
wherein the method further comprises transferring the sample to a second well using an automated sample manipulation apparatus; and
wherein applying the magnetic field comprises applying the magnetic field using the automated sample manipulation apparatus while the sample is in the second well to secure the bead complex at a wall of the second well.
17 . The method of claim 16 , wherein applying the magnetic field includes moving, via the automated sample manipulation apparatus, a magnet into position relative to the second well such that the magnet provides the magnetic field within the second well.
18 . The method of claim 16 , wherein applying the magnetic field includes moving, via the automated sample manipulation apparatus, the second well into position relative to a magnet such that the magnet provides the magnetic field within the second well.
19 . The method of claim 16 , wherein applying the magnetic field includes activating, via the automated sample manipulation apparatus, an electromagnet in a position relative to the second well such that the electromagnet provides the magnetic field within the second well.