Thermocycling inspection device and chip holder

Inventors

Sekizawa, RyuichiAso, RyokoMITSUTAKE, Hiroshi

Assignees

METABOSCREEN CO Ltd

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Publication Number

US-11958052-B2

Patent

Publication Date

2024-04-16

Expiration Date


Abstract

The thermocycling inspection device includes a holder-accommodating space 10 for accommodating the chip holder 50 therein, a thermocycling section 20 for heating and cooling the inspection chip 60, and a detector 30 for taking a picture of the inspection chip 60, and when the thermocycling section 20 heats or cools or when a picture is taken by the detector 30, the thermocycling section 20 is disposed on one side of the holder-accommodating space 10, the detector 30 is disposed on other side of the holder-accommodating space 10, and the holder-accommodating space 10 is formed such that an optical axis of the detector 30 and a sample introducing port 62 match with each other. According to this, polymerase chain reaction can be carried out, and inspection can be carried out using the inspection chip which carries out the polymerase chain reaction.

Core Innovation

A thermocycling inspection device is provided for polymerase chain reaction (PCR) using an inspection chip accommodated in a chip holder. The inspection chip includes a sample introducing port and a sample discharge port in a central portion, and a plurality of sample flow passages radially extending from the sample introducing port. The inspection chip is configured to fix a reagent to the plurality of sample flow passages by capillary action, enabling inspection by polymerase chain reaction using the chip holder and a thermocycler that heats and cools the inspection chip.

The device includes a detector that takes a picture of the inspection chip. The thermocycler has an upper surface on which the chip holder is disposed, and a pair of slide rails moves the thermocycler including the chip holder such that an optical axis of the detector and an optical axis of the sample introducing port match with each other. This optical axis matching is maintained when the thermocycler heats or cools the inspection chip and when a picture of the inspection chip is taken by the detector.

The chip holder includes a chip-accommodating saucer, a holder having an upper surface comprising a ring-shaped recess, positioning recesses and fixing holes, and a chip-pressing device configured to press the inspection chip accommodated in the chip-accommodating saucer against the chip-accommodating saucer. The ring-shaped recess is formed around an outer periphery of the chip-accommodating saucer, and the chip-pressing device includes a ring portion, positioning legs, fixing projections and chip pressing legs that are mounted on the ring-shaped recess and positioning recesses, and fixed by fitting the fixing projections into the fixing holes. This arrangement positions and fixes the chip-pressing device on the holder.

In further refinements, the thermocycler includes a Peltier element for heating and cooling, with heat sink and heater arranged to enable heating of the accommodated inspection chip. A temperature sensor is disposed between the heater and the chip-accommodating saucer, and fluorescence detection components are included by a fluorescence detection window and a transparent substrate that presses the chip holder. The stated operation is a sample-to-result inspection using thermocycling PCR with detector imaging.

Claims Coverage

The claim set covers a thermocycling inspection device for polymerase chain reaction (PCR) with imaging alignment during heating and cooling and chip holder structures that fix a reagent by capillary action. It includes 7 inventive features.

Pcr thermocycling inspection chip with capillary reagent fixation

An inspection chip having a sample introducing port and a sample discharge port in a central portion, and a plurality of sample flow passages radially extending from the sample introducing port; a chip configured to fix a reagent to the plurality of sample flow passages by capillary action; the specimen inspected by polymerase chain reaction using the chip holder and a thermocycler that heats and cools the inspection chip.

Detector imaging with slide-rail optical axis matching to the sample introducing port

A detector that takes a picture of the inspection chip; the chip holder disposed on the upper surface of the thermocycler; and a pair of slide rails that moves the thermocycler including the chip holder such that an optical axis of the detector and an optical axis of the sample introducing port match with each other when the thermocycler heats or cools the inspection chip or when a picture of the inspection chip is taken by the detector.

Chip holder saucer and pressing structure with ring recess, positioning recesses, and fixing holes

A chip holder including a chip-accommodating saucer; a holder configured to hold the chip-accommodating saucer at a central portion with an upper surface comprising a ring-shaped recess, positioning recesses and fixing holes; and a chip-pressing device configured to press the inspection chip accommodated in the chip-accommodating saucer against the chip-accommodating saucer, where the chip-pressing device comprises a ring portion, positioning legs, fixing projections and chip pressing legs, with the ring portion mounted on the ring-shaped recess, the positioning legs mounted on the positioning recesses, and fixing projections fitted into corresponding fixing holes to position and fix the chip-pressing device.

Peltier-based thermocycler heating via heat sink, heater, and cover plate opening

A thermocycler including a Peltier element, a heat sink and a heater arranged on opposite surfaces of the Peltier element, and a cover plate with an opening that enables a chip holder saucer to contact the heater so the accommodated inspection chip is heated by the heater.

Temperature sensing between heater and chip-accommodating saucer

A temperature sensor placed between the heater and the chip-accommodating saucer.

Fluorescence detection window with transparent substrate pressing the chip holder

A holder-pressing lid including a fluorescence detection window, and a transparent substrate that covers the window and presses the chip holder.

Cooling-heating relationship among peltier element, heater, and temperature sensor

A thermocycler includes a Peltier element, a heater, and a temperature sensor that detects the temperature of an inspection chip, where the heater heats the inspection chip and the Peltier element cools the heater.

The claim set centers on performing PCR on a chip-based inspection chip with reagent fixation by capillary action, imaging the inspection chip using a detector whose optical axis is aligned via slide rails during thermocycling, and mechanically fixing the chip using a saucer plus a ring recess, positioning recesses, and fixing holes pressing structure. Dependent refinements narrow the thermocycler to a Peltier-based heater/cooler architecture with a temperature sensor and add fluorescence detection by a fluorescence detection window and a transparent substrate that presses the chip holder.

Stated Advantages

Enables sample-to-result inspection with thermocycling PCR using detector imaging.

Documented Applications

Polymerase chain reaction (PCR) inspection and real-time inspection (POCT) using a thermocycling inspection device with imaging by a detector.

Industrial applicability for sample-to-result operation stated as approximately 15 minutes.

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