Systems and methods for detection of cells using engineered transduction particles
First Claim
1. A method of detecting the presence a target cell within a biological sample using an instrument, comprising:
- conveying a plurality of transduction particles associated with the target cell from a reagent module into a sample container containing the biological sample, the reagent module coupled to the sample container during the conveying such that the sample container is fluidically isolated from an exterior volume, the plurality of transduction particles engineered to be non-replicative and to include a nucleic acid molecule formulated to cause the target cell to produce a plurality of reporter molecules, the plurality of transduction particles formulated to bind to and deliver the nucleic acid molecule into the target cell;
maintaining, after the conveying, the biological sample and the plurality of transduction particles within the sample container for a time period to allow the plurality of reporter molecules to be produced within the sample container when the target cell is present in the biological sample;
exerting a force on the reagent module to place a seal surface of the reagent module in contact with a corresponding surface of the instrument to optically isolate the sample container from the exterior volume, the seal surface in a fixed location relative to the sample container;
conveying, after the exerting, a reagent from the reagent module into the sample container, the reagent formulated to react with the plurality of reporter molecules to catalyze production of a signal, the seal surface being maintained in contact with the corresponding surface during the conveying the reagent; and
receiving via a detector of the instrument, the signal associated with a quantity of the plurality of reporter molecules.
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Abstract
Systems and methods for detecting and/or identifying target cells (e.g., bacteria) using engineered transduction particles are described herein. In some embodiments, a method includes mixing a quantity of transduction particles within a sample. The transduction particles are associated with a target cell. The transduction particles are non-replicative, and are engineered to include a nucleic acid molecule formulated to cause the target cell to produce a series of reporter molecules. The sample and the transduction particles are maintained to express the series of the reporter molecules when target cell is present in the sample. A signal associated with a quantity of the reporter molecules is received. In some embodiments, a magnitude of the signal is independent from a quantity of the transduction particle above a predetermined quantity.
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Citations
19 Claims
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1. A method of detecting the presence a target cell within a biological sample using an instrument, comprising:
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conveying a plurality of transduction particles associated with the target cell from a reagent module into a sample container containing the biological sample, the reagent module coupled to the sample container during the conveying such that the sample container is fluidically isolated from an exterior volume, the plurality of transduction particles engineered to be non-replicative and to include a nucleic acid molecule formulated to cause the target cell to produce a plurality of reporter molecules, the plurality of transduction particles formulated to bind to and deliver the nucleic acid molecule into the target cell; maintaining, after the conveying, the biological sample and the plurality of transduction particles within the sample container for a time period to allow the plurality of reporter molecules to be produced within the sample container when the target cell is present in the biological sample; exerting a force on the reagent module to place a seal surface of the reagent module in contact with a corresponding surface of the instrument to optically isolate the sample container from the exterior volume, the seal surface in a fixed location relative to the sample container; conveying, after the exerting, a reagent from the reagent module into the sample container, the reagent formulated to react with the plurality of reporter molecules to catalyze production of a signal, the seal surface being maintained in contact with the corresponding surface during the conveying the reagent; and receiving via a detector of the instrument, the signal associated with a quantity of the plurality of reporter molecules. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A method of detecting the presence of a target cell within a biological sample, comprising:
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coupling a reagent module to a sample container such that a reaction chamber defined by the sample container is fluidically isolated from an exterior volume, the reaction chamber containing the biological sample, the reagent module containing a plurality of transduction particles associated with the target cell and a reagent; disposing, after the coupling, at least a distal end portion of the sample container into an instrument; and actuating the instrument to cause the instrument to; manipulate the reagent module to convey the plurality of transduction particles into the reaction chamber of the sample container, the plurality of transduction particles associated with a target cell, the plurality of transduction particles engineered to be non-replicative and to include a nucleic acid molecule formulated to cause the target cell to produce a plurality of reporter molecules; maintain the biological sample and the plurality of transduction particles within the reaction chamber within a predetermined temperature range to allow the plurality of reporter molecules to be produced within the reaction chamber when the target cell is present in the biological sample; move the reagent module within the instrument to place a seal surface of the reagent module contact with a corresponding surface of the instrument to optically isolate the reaction chamber from the exterior volume, the seal surface in a fixed location relative to the sample container; manipulate the reagent module to convey the reagent into the reaction chamber of the sample container, the reagent formulated to react with the plurality of reporter molecules to catalyze production of a signal, the seal surface being maintained in contact with the corresponding surface when the reagent module is manipulated; and receive the signal associated with a quantity of the plurality of reporter molecules. - View Dependent Claims (11, 12, 13, 14)
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15. A method of detecting the presence of a target cell within a biological sample, comprising:
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coupling a reagent module to a sample container such that a reaction chamber defined by the sample container is fluidically isolated from an exterior volume, the reaction chamber containing the biological sample, the reaction chamber devoid of a reporter molecule before the coupling, the reagent module defining a first volume and a second volume, the first volume containing a plurality of transduction particles associated with the target cell, the second volume containing a reagent; disposing, after the coupling, at least a distal end portion of the sample container into an instrument; and actuating the instrument to cause the instrument to; manipulate the reagent module to convey the plurality of transduction particles from the first volume into the reaction chamber of the sample container, the plurality of transduction particles associated with the target cell, the plurality of transduction particles engineered to be non-replicative and to include a nucleic acid molecule formulated to cause the target cell to produce a plurality of reporter molecules; maintain the biological sample and the plurality of transduction particles within the reaction chamber in fluidic isolation from the exterior volume for a time period to allow the plurality of reporter molecules to be produced within the reaction chamber when the target cell is present in the biological sample; exert a force on the reagent module to place a seal surface of the reagent module in contact with a corresponding surface of the instrument to optically isolate the reaction chamber from the exterior volume, the seal surface in a fixed location relative to the sample container; manipulate the reagent module to convey the reagent from the second volume into the reaction chamber of the sample container, the reagent formulated to react with the plurality of reporter molecules to catalyze production of a signal, the seal surface being maintained in contact with the corresponding surface when the reagent module is manipulated; and receive the signal associated with a quantity of the plurality of reporter molecules. - View Dependent Claims (16, 17, 18, 19)
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Specification