Systems and methods for detection of cells using engineered transduction particles

摘要

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.

主权项

1. A method of detecting a target cell present in a sample, the method comprising the steps of:
(a) providing the sample in a sample container; (b) mixing the sample with a plurality of transduction particles capable of binding to the target cell, the plurality of transduction particles characterized by being engineered to include a nucleic acid molecule formulated to cause the target cell to produce a plurality of reporter molecules, the plurality of transduction particles further characterized by being devoid of a wild-type DNA capable of exhibiting wild-type viral functions associated with a virus from which the plurality of transduction particles is derived; (c) maintaining the sample and the plurality of transduction particles to express the plurality of reporter molecules when the target cell is present in the sample; and (d) receiving a signal associated with a quantity of the plurality of reporter molecules, a magnitude of the signal being independent from a quantity of the plurality of transduction particles above a predetermined quantity, thereby detecting the presence of the target cell; wherein said steps (b), (c), and (d) are performed in the sample container in an apparatus, the apparatus comprising: a housing defining a channel configured to receive the sample container, the housing defining a detection volume configured to place the channel in communication with a detector, the housing including a first seal surface and a second seal surface, a first portion of the sample container and the first seal surface configured to isolate the detection volume from a volume outside of the housing when a second portion of the sample container is disposed within the detection volume; and a shutter having a portion movably disposed within the housing between a first shutter position and a second shutter position, the shutter defining a port configured to receive at least one of a light source or a light guide, a seal surface of the shutter and the second seal surface configured to isolate the detection volume from the channel of the housing when shutter is in the first shutter position, the port in communication with the detection volume when the shutter is in the first shutter position, the channel of the housing being in communication with the detection volume when the shutter is in the second shutter position, the port being isolated from the detection volume when the shutter is in the second shutter position.