Optical system and assay chip for probing, detecting and analyzing molecules

An instrument configured to interface with an assay chip comprising a plurality of sample wells, each sample well of the plurality of sample wells configured to receive a sample, the instrument comprising:

• at least one excitation light source configured to excite the sample of at least a portion of the plurality of sample wells;
• a plurality of sensors, each sensor of the plurality of sensors corresponding to a sample well of the plurality of sample wells, wherein each sensor of the plurality of sensors is configured to detect emission energy from the sample in a respective sample well;
• and
• at least one optical element configured to direct the emission energy from each sample well of the plurality of sample wells towards a respective sensor of the plurality of sensors.

An apparatus comprising:

• an assay chip comprising a plurality of pixels, each of the plurality of pixels comprising:
• a sample well configured to receive a sample, which, when excited, emits emission energy;
• at least one element for directing the emission energy in a particular direction, wherein the at least one element is selected from the group consisting of a refractive element, a diffractive element, a plasmonic element and a resonator;
• and
• a light path along which the emission energy travels from the sample well toward a sensor;
• and
• an instrument configured to interface with the assay chip, the instrument comprising:
• at least one excitation light source configured to excite the sample in each sample well;
• a plurality of sensors, each sensor of the plurality of sensors corresponding to a respective sample well, wherein each sensor of the plurality of sensors is configured to detect emission energy from the sample in the respective sample well;
• and
• at least one optical element configured to direct the emission energy from each sample well towards a respective sensor of the plurality of sensors.

A method of analyzing a specimen, the method comprising:

• providing the specimen on the top surface of an assay chip comprising a plurality of sample wells;
• aligning the chip with an instrument comprising at least one excitation light source and at least one sensor;
• exciting a sample from the specimen in at least one of the plurality of sample wells with excitation light from the at least one excitation light source;
• and
• detecting, with the at least one sensor, emission energy generated by the sample in the at least one sample well in response to excitation by the excitation light.

A method for sequencing a target nucleic acid molecule, comprising:

• (a) providing a chip adjacent to an instrument that includes an excitation source and a sensor, wherein said chip includes at least one well that is operatively coupled to said excitation source and said sensor when said chip is at a sensing position of said instrument, and wherein said well contains said target nucleic acid molecule, a polymerizing enzyme and a plurality of types of nucleotides or nucleotide analogs;
• (b) with said chip at said sensing position, performing an extension reaction at a priming location of said target nucleic acid molecule in the presence of said polymerizing enzyme to sequentially incorporate said nucleotides or nucleotide analogs into a growing strand that is complementary to said target nucleic acid molecule, wherein upon incorporation and excitation by excitation energy from said excitation source, said nucleotides or nucleotides analogs emit signals in said well;
• (c) using said sensor to detect spatial and/or temporal distribution patterns of said signals that are distinguishable for said plurality of types of nucleotides or nucleotide analogs;
• and
• (d) identifying said nucleotides or nucleotide analogs based on said spatial and/or temporal distribution patterns of said signals, thereby sequencing said target nucleic acid molecule.

A method for nucleic acid sequencing, comprising:

• (a) providing a chip adjacent to an instrument, wherein said chip includes a plurality of wells that are each operatively coupled to (i) an excitation source and (ii) a sensor of said instrument when said chip is at a sensing position of said instrument, and wherein an individual well of said plurality contains said target nucleic acid molecule, a polymerizing enzyme and a plurality of types of nucleotides or nucleotide analogs;
• (b) with said chip at said sensing position, subjecting said target nucleic acid molecule to a polymerization reaction to yield a growing strand that is complementary to said target nucleic acid molecule in the presence of said nucleotides or nucleotide analogs and said polymerizing enzyme, wherein said nucleotides or nucleotides analogs emit signals in said individual well upon excitation by excitation energy from said excitation source during incorporation;
• (c) using said sensor to detect spatial and/or temporal distribution patterns of said signals that are distinguishable for said plurality of types of nucleotides or nucleotide analogs;
• and
• (d) identifying a sequence of said target nucleic acid molecule based on said spatial and/or temporal distribution patterns of said signals.