SPHERICAL ENCODED BEADS

• US 20090032592A1
• Filed: 01/11/2007
• Published: 02/05/2009
• Est. Priority Date: 01/11/2006
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Christensen, Soren Flygenring
• Application Number:
  US12/160,306
• Publication Number:
  US 20090032592A1
• Time in Patent Office: Days
• US Class Current: 235/439
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00565 Electromagnetic means
• CPC Class Codes: B01J 2219/00567 Transponder chips
• CPC Class Codes: C40B 60/02 Integrated apparatus specially adapted for creating libraries, screening libraries and for identifying library members
• CPC Class Codes: G01N 2035/00574 Means for distributing beads
• CPC Class Codes: G01N 2035/00782 reprogrammmable code
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer

Abstract

The present application discloses a composition comprising a plurality of spherical beads, wherein a radiofrequency chip operating at a frequency of in the range of 2.2-2.7 GHz is embedded within each of said beads and wherein essentially each of said beads is individually identifiable on the basis of radiofrequency identification. Alternatives utilizing a ultrasonic identification chip are also disclosed. The beads are preferably made of polymeric material and can for example be used for the synthesis of e.g. solid-phase chemical libraries. Preferred materials include some that minimise interference in biochemical assays (fouling). The invention also relates to batch and continuous methods of producing such compositions, including emulsion-polymerisation methods. In a further aspect, the present invention relates to an apparatus for analysing radiofrequency-encoded beads. Also provided are methods for detecting and/or analysing and/or sorting beads, as well as methods for processing beads once they have been analysed and/or sorted.

Claims

1-65. -65. (canceled)

66. An apparatus for analyzing a plurality of spherical radiofrequency-identifiable beads, said apparatus comprising

i) a vacuum container comprising at least one planar capture body capable of rotating around a central axis,

wherein said capture body comprises a plurality of through-going inlets arranged substantially concentrically around the central axis of the capture body,

wherein the diameter of each inlet is smaller than the average diameter of the beads to be detected,

ii) a pressure-controlling device capable of controlling the pressure in the vacuum container,

iii) a guiding channel enclosing said plurality of inlets;

iv) a device for rotating the vacuum container around the axis of the capture body, and

v) a detection device for determining the radiofrequency code of said bead; and

wherein the planar capture body is arranged in a tilted manner at least 15°

off a horizontal arrangement and so that the detection device is positioned in or in close proximity of the upper half of the guiding channel.

72. A method for detecting a radiofrequency code of at least one bead of a plurality of beads, said method comprising the steps of

i) providing a plurality of beads each comprising a radiofrequency code,

ii) providing an apparatus according to any one of the claims 66-68 for analyzing a plurality of spherical radiofrequency-identifiable beads,

iii) contacting at least one bead of the plurality of beads provided in step i) with the vacuum container capture body of the apparatus provided in step ii),

iv) rotating the capture body to transfer at least one bead from the loading section of the vacuum container to the detection section of the vacuum container, and

v) using the detection device of the apparatus for determining the radiofrequency code of the at least one bead.

73. A method for identifying at least one bead of a plurality of beads, said method comprising the steps of

i) providing a plurality of beads each comprising a radiofrequency code,

ii) providing an apparatus according to any one of the claims 66-68 for analyzing a plurality of spherical radiofrequency-identifiable beads,

iii) contacting at least one bead of the plurality of beads provided in step i) with the vacuum container capture body of the apparatus provided in step ii),

iv) rotating the capture body to transfer at least one bead from the loading section of the vacuum container to the detection section of the vacuum container,

v) using the detection device of the apparatus for detecting the radiofrequency code of the at least one bead,

vi) using the analyzing device for analyzing data generated by the detection device, and

vii) identifying at least one bead of a plurality of beads by analyzing the data generated by the detection device.

74. A method for sorting at least one bead of a plurality of beads, said method comprising the steps of

i) providing a plurality of beads each comprising a radiofrequency code,

ii) providing an apparatus according to any one of the claims 66-68 for sorting a plurality of beads,

iii) contacting at least one bead of the plurality of beads provided in step i) with the vacuum container capture body of the apparatus provided in step ii),

iv) rotating the capture body to transfer at least one bead from the loading section of the vacuum container to the detection section of the vacuum container,

v) using the detection device of the apparatus for detection the radiofrequency code of said at least one bead,

vi) using the analyzing device for analyzing data generated by the detection device, and

sorting the at least one bead of a plurality of beads based on the result of the analysis performed in step vi).

75. A method for treating at least one bead of a plurality of beads, such as polymer beads, said method comprising the steps of

i) providing a plurality of beads each comprising a radiofrequency code,

ii) providing an apparatus according to any one of the claims 66-68 for treating at least one bead,

iii) contacting at least one bead of the plurality of beads provided in step i) with the vacuum container capture body of the apparatus provided in step ii),

iv) rotating the capture body to transfer at least one bead from the loading section of the vacuum container to the detection section of the vacuum container,

v) using the detection device of the apparatus for detection the radiofrequency code of at least one bead,

vi) analyzing data generated by the detection device, and

vii) treating at least one bead of a plurality of beads based on the result of the analysis performed in step vi).

67. An apparatus for analyzing a plurality of spherical radiofrequency-identifiable beads, said apparatus comprising

i) a vacuum container comprising at least one planar capture body capable of rotating around a central axis,

wherein said capture body comprises a plurality of through-going inlets arranged substantially concentrically around the central axis of the capture body,

wherein the diameter of each inlet is smaller than the average diameter of the beads to be detected,

ii) a pressure-controlling device capable of controlling the pressure in the vacuum container,

iii) a guiding channel enclosing said plurality of inlets;

iv) a device for rotating the vacuum container around the axis of the capture body, and

v) a detection device comprising at plurality of antennas for emitting and receiving radiofrequency electromagnetic irradiation for determining the radiofrequency code of said beads, at least some of said antennas being positioned at each of said through-going inlets of said capture body.

68. An apparatus for analyzing a plurality of spherical radiofrequency-identifiable beads, said apparatus comprising

i) a vacuum container comprising at least one planar capture body capable of rotating around a central axis,

wherein said capture body comprises a plurality of through-going inlets arranged substantially concentrically around the central axis of the capture body,

wherein the diameter of each inlet is smaller than the average diameter of the beads to be detected,

ii) a pressure-controlling device capable of controlling the pressure in the vacuum container,

iii) a guiding channel enclosing said plurality of inlets;

a device for rotating the vacuum container around the axis of the capture body,

v) a detection device comprising at least one antenna for emitting and receiving radiofrequency electromagnetic irradiation operating at a frequency of in the range of 2.2-2.7 GHz for determining the radiofrequency code of said beads.

69. A method for the production of a composition comprising a plurality of spherical radiofrequency-identifiable polymeric beads comprising the steps of:

i) providing a first liquid,

ii) providing a second liquid comprising monomers to be polymerised and, optionally, a surfactant,

wherein said first and second liquid are immiscible,

iii) providing a plurality of radiofrequency chips operating at a frequency of in the range of 2.2-2.7 GHz, optionally coated with an initiator of polymerisation,

wherein said optionally coated radiofrequency chips are capable of dispersing into the second liquid,

iv) mixing said first liquid, said second liquid and said plurality of radiofrequency chips, in any order, such that an emulsion is formed wherein said radiofrequency chips disperse into droplets of said second liquid,

v) optionally introducing an initiator if not provided in step iii), and

vi) allowing the formation of spherical polymeric beads having an embedded radiofrequency chip.

70. A method for the production of a composition comprising a plurality of spherical radiofrequency-identifiable polymeric beads comprising the steps of:

i) providing a first stream of a first liquid material,

ii) introducing into said first stream of liquid material, a second stream of monomers

for the formation of a polymer, said stream further comprising a plurality of radiofrequency chips operating at a frequency of in the range of 2.2-2.7 GHz, and, optionally a surfactant,

wherein the first liquid material and the monomers of the second stream are immiscible,

iii) regulating said second stream such that spherical droplets having embedded a radiofrequency chip are formed, and

iv) allowing the formation of spherical polymeric beads having embedded a radiofrequency chip from said droplets,

said method further comprising, during one of the above steps, addition of an initiator of polymerisation, wherein addition of the initiator or activation of the initiator is timed in such a way that polymerisation is initiated simultaneously with, or after, the formation of droplets.

71. A composition comprising a plurality of spherical beads, wherein a radiofrequency chip operating at a frequency of in the range of 2.2-2.7 GHz is embedded within each of said beads and wherein essentially each of said beads is individually identifiable on the basis of radiofrequency identification.

76. A method for recording individual reaction steps involved in the step-wise synthesis of a chemical compound on a radiofrequency-detectable bead, said method comprising the steps of

i) immobilizing a radiofrequency chip in each of a plurality of beads,

ii) isolating, preferably by automated selection, at least a subset of the beads provided in step a),

iii) recording and storing a radiofrequency identification number for each bead,

iv) step-wise synthesizing chemical compounds on functional groups present on the beads, wherein the identity of each bead is recorded and stored for each reaction step, and

obtaining for each bead a record of the individual reaction steps.

77. A method for identifying a chemical compound having been synthesized on a radiofrequency-detectable bead, said method comprising the steps of

i) performing the recording method of claim 76,

ii) selecting beads of interest by using an assay or a diagnostic screen selective for

the chemical compound having been synthesized on the bead,

iii) recording the radiofrequency code for each of the beads selected in step ii),

iv) comparing the radiofrequency code recorded in step iii) with all of the radiofrequency codes recorded and stored in step iii) of claim 76, thereby obtaining information about the identity of the selected bead,

v) identifying for each selected bead the sequence of individual steps having lead to the synthesis of the chemical compound, and

vi) identifying, based the sequence of individual steps, the chemical structure of the compound.