Apparatus and method for monitoring molecular species within a medium

• US 7,115,229 B2
• Filed: 09/24/2001
• Issued: 10/03/2006
• Est. Priority Date: 06/14/1999
• Status: Expired due to Term

• Current Assignee: Alpha M.O.S.
• Original Assignee: Alpha M.O.S.
• Inventors: Zenhausern, Frederic
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US09/961,904
• Publication Number:
  US 20020094531A1
• Time in Patent Office: 1,835 Days
• Field of Search: 435/6, 435/7.1, 435/7.2, 435/7.3, 435/7.4, 435/287.1, 435/288.2, 435/288.3, 435/320.1, 435/252.8, 435/174, 435/183, 422/58, 422/68.1, 422/119, 382/129, 382/133, 382/153, 382/173, 382/286, 382/291, 536/22.1
• US Class Current: 422/68.1
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2561/113 Real time assay
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: G16B 40/20 Supervised data analysis
• CPC Class Codes: Y10S 977/924 using nanostructure as support of dna analysis

Abstract

Apparatus and methods for monitoring, analyzing, and/or discriminating molecular species, preferably a biomolecule, within a medium using a multisensor array (MSA) and multivariate processing. Biological compounds such as nucleotides and polynucleotides can be detected and analyzed. A reaction process such as an accumulation cycle of nucleic acids can be monitored, analyzed, and controlled using a multisensor array (MSA) and multivariate processing. Monitoring a biomolecule includes interrogating the medium, and preferably its gas phase, by coupling a sensor responsive to any changes of the medium and or biomolecule and its secondary products when, for example, an amplification reaction is proceeded. It is also a scope of the present invention to use direct detection and monitoring of biomolecular reactions in real-time without radioactive or fluorescent labeling. A preferred application is real-time polymerase chain reaction (PCR) detection.

Claims

1. An apparatus for analyzing at least one unlabelled biomolecule selected from the group consisting of protein, lipid, carbohydrate and nucleic acid, during a reaction process, by monitoring volatile compounds directly in-situ within a gas or vapor phase medium from the reaction, comprising:

a multisensor array capable of detecting and discriminating more than one physico-chemical change of a gas or vapor phase of an unlabelled biomolecule or a product thereof, directly from the medium in-situ wherein the multisensor array comprises at least one metal oxide semiconductor;

transmission means, capable of transmitting a signal between the multisensor array and a data acquisition system, capable of converting the signal into raw data;

a computational device capable of processing at least part of the raw data using multivariate analysis to create a data set; and

an output device capable of displaying, storing, or using the data set.

2. The apparatus according to claim 1, wherein the output device is a feedback control capable of using the data set to control a biological amplification process.

3. The apparatus according to claim 2, wherein the biomolecule is a nucleic acid, and the feedback controls a polymerase chain reaction in approximately real time.

4. An apparatus for controlling a nucleic acid replication process, comprising:

a multisensor array capable of detecting and discriminating more than one physico-chemical change of a gas or vapor phase of a nucleic acid or a product thereof within a gas or vapor phase medium, and generating an output;

a computational device capable of processing the output using multivariate analysis to create a data set; and

a feedback control capable of using the data set to control the replication process.

5. The apparatus according to claim 4, wherein the multisensor array comprises at least one metal oxide semiconductor and the feedback controls a polymerase chain reaction in real time.

6. An apparatus for detecting at least one of a bacteria, bacteriophage, or a virus, comprising:

a multisensor array capable of detecting and discriminating more than one physico-chemical change within a gas or vapor phase of an unlabelled nucleic acid extracted from the bacteria bacteriophage or virus, or unlabelled product of said nucleic acid, from a medium in situ, wherein the multisensor array comprises at least one metal oxide semiconductor;

means for generating an output;

a computational device capable of processing the output using multivariate analysis to create a data set; and

an output device capable of displaying, storing, or using the data set.

7. An apparatus for analyzing at least one of a bacteria, a bacteriophage, or a virus, comprising:

a multisensor array capable of detecting and discriminating more than one physico-chernical change within a gas or vapor phase of an unlabelled nucleic acid or an unlabelled product thereof created or modified by the bacteria, the bacteriophage, or the virus, from a medium in situ, wherein the multisensor array comprises at least one metal oxide semiconductor,

and generating an output;

a computational device capable of processing the output using multivariate analysis to create a data set; and

an output device capable of displaying, storing, or using the data set.