Integrated nucleic acid analysis system for MALDI-TOF MS
First Claim
1. An integrated nucleic acid analysis system for a MALDI-TOF mass spectrometer comprising a thin film support having:
- (a) a sample preparation compartment for receiving and handling an oligonucleotide analyte, said compartment including a well for receiving liquid substances for sample preparation, a temperature-controlled reaction zone comprising means for immobilizing a catalyst thereto for chemically manipulating an oligonucleotide analyte therein, and a microchannel interconnecting said well and said reaction zone;
(b) automatable means for moving an oligonucleotide analyte and fluids within said compartment;
(c) automatable means for controlling the temperature of said compartment over a range of about 10°
C. to about 100°
C.; and
(d) a MALDI ionization surface in communication with said sample preparation compartment through said microchannel.
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Accused Products
Abstract
An integrated nucleic acid sample analysis system for matrix-assisted laser-desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) is described. The integrated system comprises a miniaturized sample preparation compartment interfaced directly with a MALDI-TOF ionization surface for amplifying and/or otherwise chemically manipulating an oligonucleotide analyte and presenting the analyte to a MALDI ionization surface for mass spectrometry analysis. The miniaturized integrated sample handling system disclosed herein finds application in the amplification and analysis of DNA samples for genetic diagnosis and other uses.
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Citations
19 Claims
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1. An integrated nucleic acid analysis system for a MALDI-TOF mass spectrometer comprising a thin film support having:
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(a) a sample preparation compartment for receiving and handling an oligonucleotide analyte, said compartment including a well for receiving liquid substances for sample preparation, a temperature-controlled reaction zone comprising means for immobilizing a catalyst thereto for chemically manipulating an oligonucleotide analyte therein, and a microchannel interconnecting said well and said reaction zone; (b) automatable means for moving an oligonucleotide analyte and fluids within said compartment; (c) automatable means for controlling the temperature of said compartment over a range of about 10°
C. to about 100°
C.; and(d) a MALDI ionization surface in communication with said sample preparation compartment through said microchannel. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. An integrated nucleic acid analysis system for MALDI-TOF mass spectrometry comprising a thin film support having
(a) sample preparation compartment for receiving and handling oligonucleotide analytes, said compartment including a plurality of temperature-controlled reaction zones interconnected by microchannels to wells and capture regions, wherein said microchannels are provided with means for directing the flow of reagents and oligonucleotide analytes within said compartment and with sealing means, and said wells and capture regions are optionally provided with access ports, and one or more MALDI ionization surfaces fabricated within said compartment to communicate with at least one of said microchannels for receiving and presenting said oligonucleotide analytes to a mass spectrometer for MALDI-TOF mass spectral analysis; -
(b) an access port communicating with at least one microchannel in said sample preparation compartment; and (c) automatable means for moving said oligonucleotide analytes within said compartment.
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16. An integrated nucleic acid analysis system for MALDI-TOF mass spectrometry comprising:
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a thin film support having (a) a sample preparation compartment for receiving and handling oligonucleotide analytes, said compartment including a plurality of temperature-controlled reaction zones interconnected by microchannels to wells and capture regions within said compartment, (b) an access port communicating with at least one of said microchannels, wherein said microchannels are provided with means for directing the flow of reagents and oligonucleotide analytes within the sample preparation compartment, and said wells and capture regions are optionally provided with access ports, and (c) automatable means for moving said oligonucleotide analytes within said compartment; and a MALDI ionization surface included in a rotatable comb device, said device comprising an upper handle with downwardly extending teeth, whereupon the rotation of said device to a first position places said ionization surface in fluid communication with a microchannel for receiving said oligonucleotide analytes contained therein, and the rotation of said device to a second position aligns said ionization surface with the vacuum gate of a mass spectrometer for insertion therein. - View Dependent Claims (17, 18, 19)
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Specification