1. A method of sequence-specific amplification of assay signals produced in the analysis of a target nucleic acid sequence, the method permitting real-time monitoring of amplified signal and comprising the following steps:
(a) providing a temperature-controlled sample containment device that permits real-time recording of optical assay signals produced within said device, and a temperature control means for controlling the temperature of said device;
(b) providing within said sample containment device a set of interrogation probes, said interrogation probes being capable of forming a hybridization complex with a target nucleic acid and being attached to beads, wherein said beads are associated with a chemically or physically distinguishable characteristic that identifies the interrogation probes attached thereto;
(c) contacting said interrogation probes with the target sequence to form a hybridization complex between the interrogation probes and the target sequence;
(d) contacting said hybridization complex with a second oligonucleotide probe, said second probe comprising a label and capable of being ligated to the interrogation probes contained within the hybridization complex;
(e) providing conditions suitable for ligating said second labeled oligonucleotide probe to the interrogation probe;
(f) detecting the optical signals from the second labeled probes; and
(g) performing one or more annealing-ligating-detecting-denaturing cycles, each cycle increasing the number of ligated probes in arithmetic progression and involving the following steps:
(i) providing a first temperature for the formation of the hybridization complex;
(ii) providing a second temperature for ligase-catalyzed ligation of the interrogation probe and the second labeled probe to occur to thereby generate a ligation product, wherein ligation is associated with a change in optical signature of beads associated with the ligation product;
(iii) imaging andor recording optical signals from the ligation product thereby permitting real-time monitoring of amplified signal emanating from the ligation product; and
(iv) providing a third temperature for denaturing all hybridization complexes.
2. The method of claim 1 wherein steps (c) to (g) are repeated one or more times.
3. The composition of claim 1 wherein the target nucleic acid sequences are derived from the patient genomic sample by amplification of one or more nucleic acid subsequences within the patient genomic sample.
4. The composition of claim 3 wherein the amplification is performed using the polymerase chain reaction.
5. The method of claim 1, wherein the target nucleic acid sequence includes a mutation site or a polymorphic site and said set interrogation probes includes members designed to detect the different nucleotides at the mutation or polymorphic site.
6. The method of claim 1, wherein the target sequence includes a mutation site or a polymorphic site and the set of interrogation probes includes members capable of annealing to subsequences in the target sequence including the mutation site or the polymorphic site, within a range of proximity to the mutation site or the polymorphic site.
7. The method of claims 5 or 6, wherein the polymorphic site is a single nucleotide polymorphism.
8. The method of claims 5 or 6, wherein the polymorphic site is a short term tandem repeat site.
9. The method of claim 1 wherein the label is an inorganic nanoparticle label, including semiconductor Quantum Dot particles and Resonant Light Scattering metal nanoparticles.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of cleaning a CVD apparatus, comprising the steps of: removing contaminants adhering to the interior of a CVD by activating a cleaning gas; detecting a removal state of contaminants adhering to an inner surface of said reactor by irradiating the inner surface of said reactor with light having monochromaticity through an optical window provided on an inner wall of said reactor at a bottom of said reactor and receiving its reflected light; and controlling the cleaning step based on the detection of results, wherein prior to removing contaminants a purge gas is supplied, Directed to the vicinity of the optical window and exhausted to protect the optical window from reaction products while inhibiting the purge gas from flowing into a reaction space of the CVD reactor and the vicinity of a semiconductor wafer placed in the reaction space, wherein the purge gas is exhausted though one of two openings of an exhaust balancer, said one of the two openings being closer to the optical window than is another of the two openings, wherein the one of the two openings of the balancer is provided along a bottom surface of the reactor, and the another of the two openings of the balancer is provided along an inner wall of a reactor, wherein purge gas flows along the bottom surface of the reactor and an upper surface of the optical window and is exhausted through one of the two openings.
2. The method of cleaning a CVD apparatus according to claim 1, wherein said light having monochromaticity is monochromatic light.
3. The method of cleaning a CVD apparatus according to claim 1, wherein said light having monochromaticity is laser light.
4. The method of cleaning a CVD apparatus according to claim 1, wherein both irradiation with said light having monochromaticity and receiving of its reflected light are performed through the same optical window.
5. The method of cleaning a CVD apparatus according to claim 1, wherein said inner surface is a surface of a showerhead introducing reaction gas into the reactor.
6. The method of cleaning a CVD apparatus according to claim 5, wherein said inner surface is a plane in the vicinity of a periphery of said showerhead facing a susceptor for placing and heating a substrate thereon.
7. The method of cleaning a CVD apparatus according to claim 6, wherein said optical window is provided on an inner wall of said CVD reactor, which is situated in a direction perpendicular to said inner surface.
8. The method of cleaning a CVD apparatus according to claim 5, wherein said inner surface is a side surface in the vicinity of a periphery of said showerhead.
9. The method of cleaning a CVD apparatus according to claim 8, wherein said optical window is provided on an inner wall of said CVD reactor, which is situated in a direction perpendicular to said inner surface.
10. The method of cleaning a CVD apparatus according to claim 1, wherein said optical window is composed of sapphire.
11. The method of cleaning a CVD apparatus according to claim 1, wherein removal of said contaminants is detected by converging interference signals of reflected lights of said light having monochromaticity from said inner surface and from a surface of said contaminants.
12. The method of cleaning a CVD apparatus according to claim 1, wherein the mass of said contaminants is detected by reflected light intensity of said light having monochromaticity from said inner surface.
13. The method of cleaning a CVD apparatus according to claim 1, wherein said detection process is performed through said optical window provided at a bottom of a bottomed hole provided in an inner wall of said reactor.
14. The method of cleaning a CVD apparatus according to claim 1, wherein said activated cleaning gas is a cleaning gas excited in a remote plasma discharge chamber.
15. A method of forming a film by CVD, in which the cleaning method according to claim 1 is incorporated, which comprises the steps of:
forming a film on a substrate inside said CVD reactor;
during the film formation, introducing a purge gas for protecting a surface of said optical window from a deposition atmosphere into the vicinity of said optical window; and
after completion of the film formation, performing the cleaning according to claim 1.
16. The method of forming a film according to claim 15, which further comprises exhausting a purge gas for protecting said optical window without allowing the purge gas to flow into the deposition atmosphere during said film formation.
17. The method according to claim 1, wherein the optical window is provided in a portion recessed from the inner wall, and the purge gas is provided into the recessed portion.