The present disclosure herein relates to a diagnosis apparatus, and more particularly, to a polymerase chain reaction (PCR) diagnosis apparatus.
Recently, it has been required to develop a molecular diagnostic technology for simultaneously measuring various virus molecules. The molecular diagnostic technology may belong to the field of extraction of nucleic acids (DNA, RNA) through pre-processing of a biospecimen to be measured and the field of cloning and amplifying a particular DNA or RNA fragment through polymerase chain reaction (PCR) after the pre-processing. Furthermore, the molecular diagnostic technology may also belong to the field of measuring the strength of a fluorescent signal emitted from fluorescent light through an optical method after fluorescently labeling an amplified DNA.
The present disclosure provides a PCR diagnosis apparatus capable of reducing noise in fluorescent light.
Provided is a PCR diagnosis apparatus. This apparatus includes a PCR chip configured to store a PCR sample; a light source part configured to generate laser light to be provided to the PCR sample; an optical modulator provided between the light source part and the PCR chip and configured to selectively provide the laser light to the PCR sample according to a code; a sensor configured to detect fluorescent light generated in the PCR sample by the laser light; and a code generator connected between the optical modulator and the sensor and configured to transmit an orthogonal code to the optical modulator and the sensor.
According to an example, the light source part may include: a first laser light source configured to generate first laser light; and a second laser light source connected to the first laser light source and configured to generate second laser light having a longer wavelength than a wavelength of the first laser light.
According to an example, the first laser light source may include: a first optical fiber; a semiconductor saturable absorber mirror connected to one side of the first optical fiber; a volume Bragg grating provided to another side of the first optical fiber; and a first pump light source connected to the first optical fiber between the volume Bragg grating and the semiconductor saturable absorber mirror and configured to provide first pump light in the first optical fiber.
According to an example, the second laser light source may include: a second optical fiber branched from the first optical fiber; and a second pump light source configured to provide second pump light in the second optical fiber to generate the second laser light.
According to an example, the second laser light source may further include: a first nonlinear optical fiber connected to the second optical fiber and configured to disperse the first laser light; and a first wavelength tunable filter configured to tune the wavelength of the first laser light.
According to an example, the light source part may further include a third laser light source connected to the first laser light source and configured to generate third laser light having a shorter wavelength than the wavelength of the first laser light.
According to an example, the third laser light source may include: a third optical fiber branched from the first optical fiber; and a third pump light source configured to provide third pump light in the third optical fiber to generate the third laser light.
According to an example, the third laser light source may further include: a second nonlinear optical fiber connected to the third optical fiber and configured to disperse the first laser light; and a second wavelength tunable filter configured to tune the wavelength of the first laser light.
According to an example, the first nonlinear optical fiber may include a first core having a first diameter, and the second nonlinear optical fiber may include a second core having a second diameter smaller than the first diameter.
According to an example, the optical modulator may include a digital mirror device, a liquid crystal display device, or a spatial optical modulator.
A PCR diagnosis apparatus according to an example of the inventive concept includes: a first laser light source configured to generate first laser light using first pump light; a second laser light source configured to generate second laser light having a longer wavelength than a wavelength of the first laser light using second pump light having a longer wavelength than a wavelength of the first pump light; a third laser light source configured to generate third laser light having a shorter wavelength than the wavelength of the first laser light using third pump light having a shorter wavelength than the wavelength of the first pump light; a PCR chip configured to store a sample generating fluorescent light by receiving the first to third laser light; an optical modulator provided between the PCR chip and the first to third laser light sources and configured to provide the first to third laser light to the sample; a sensor provided on one side of the PCR chip opposing the optical modulator and configured to detect the fluorescent light; and code control parts connected to the sensor and the optical modulator and configured to switch the first to third laser light respectively using an orthogonal code.
According to an example, the first laser light source may include: a first optical fiber; a semiconductor saturable absorber mirror provided to one side of the first optical fiber; a volume Bragg grating provided to another side of the first optical fiber; and a first pump light source connected to the first optical fiber between the volume Bragg grating and the semiconductor saturable absorber mirror and configured to provide the first pump light in the first optical fiber.
According to an example, the second laser light source may include: a second optical fiber branched from the first optical fiber; a second pump light source configured to provide the second pump light in the second optical fiber; and a first nonlinear optical fiber connected to the second optical fiber and configured to disperse the first laser light.
According to an example, the third laser light source may include: a third optical fiber branched from the first optical fiber; a third pump light source configured to provide the third pump light in the third optical fiber; and a second nonlinear optical fiber connected to the third optical fiber and configured to disperse the first laser light.
According to an example, the second laser light source may further include a first wavelength tunable filter arranged between the first nonlinear optical fiber and the second pump light source and configured to tune the wavelength of the first laser light, and the third laser light source may further include a second wavelength tunable filter arranged between the second nonlinear optical fiber and the third pump light source and configured to tune the wavelength of the first laser light.
A PCR diagnosis apparatus according to an example of the inventive concept includes: a first laser light source configured to generate first laser light; a second laser light source configured to generate second laser light having a longer wavelength than a wavelength of the first laser light and including a first nonlinear optical fiber dispersing the first laser light; a third laser light source configured to generate third laser light having a shorter wavelength than the wavelength of the second laser light and including a second nonlinear optical fiber dispersing the first laser light; a PCR chip configured to store a sample generating fluorescent light by receiving the first to third laser light; an optical modulator provided between the PCR chip and the first to third laser light sources and configured to provide the first to third laser light to the sample; a sensor provided on one side of the PCR chip opposing the optical modulator and configured to detect the fluorescent light; and code control parts connected to the sensor and the optical modulator and configured to switch the first to third laser light respectively using an orthogonal code.
According to an example, the first nonlinear optical fiber may include: first cladding; and a first core arranged in the first cladding and having a first diameter.
According to an example, the second nonlinear optical fiber may include: second cladding that is the same as the first cladding; and a second core arranged in the second cladding and having a second diameter smaller than the first diameter.
According to an example, the second laser light source may further include a first wavelength tunable filter provided adjacent to the first nonlinear optical fiber and configured to tune the wavelength of the first laser light.
According to an example, the third laser light source may further include a second wavelength tunable filter provided adjacent to the second nonlinear optical fiber and configured to tune the wavelength of the first laser light.
The accompanying drawings are included to provide a further understanding of the inventive concept, and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments of the inventive concept and, together with the description, serve to explain principles of the inventive concept. In the drawings:
Embodiments of the inventive concept will now be described in detail with reference
to the accompanying drawings. The advantages and features of embodiments of the inventive concept, and methods for achieving the advantages and features will be apparent from the embodiments described in detail below with reference to the accompanying drawings. However, the inventive concept may be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the inventive concept to those skilled in the art, and the inventive concept is only defined by the scope of the claims. Like reference numerals refer to like elements throughout.
The terminology used herein is not for delimiting the embodiments of the inventive concept but for describing the embodiments of the inventive concept. The terms of a singular form may include plural forms unless otherwise specified. It will be further understood that the terms “includes”, “including”, “comprises”, and/or “comprising”, when used in this description, specify the presence of stated elements, steps, operations, and/or components, but do not preclude the presence or addition of one or more other elements, steps, operations, and/or components. Furthermore, in the present disclosure, the terms “laser”, “code”, and “two-photon” may be understood as optical, bio, and medical terms. Reference numerals, which are presented in the order of description, are provided according to the embodiments and are thus not necessarily limited to the order.
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A first lens 210 may be provided between the optical modulator 200 and the PCR chip 300. The first lens 210 may provide the laser light 101 reflected from the optical modulator 200 to the PCR chip 300, and may relay the laser light 101 in an image form on the optical modulator 200.
The PCR chip 300 may store the sample 310 in a matrix form. The PCR chip 300 may store one to m×n number of samples 310. Each sample 310 may be delivered by the optical modulator 200 through the laser light 101 having one to m×n codes.
The sensor 400 may be provided on one side of the PCR chip 300 opposing the optical modulator 200. The sensor 400 may receive the fluorescent light 108 and may analyze a DNA in the sample 310 based on the orthogonal code.
A second lens 410 may be provided between the PCR chip 300 and the sensor 400. The second lens 410 may concentrate the fluorescent light 108 on the sensor 400. The second lens 410 may include a convex lens.
A filter 420 may be provided between the second lens 410 and the sensor 400. The filter 420 may remove the laser light 101 and may pass the fluorescent light 108. The filter 420 may include a color filter such as an acrylic or cellulose film, but an embodiment of the inventive concept is not limited thereto.
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The laser light 101 may be femtosecond laser light. When the sample 310 having a certain DNA sample absorbs at a wavelength of about 400 nm and the fluorescent light 108 exhibits a wavelength of about 450 nm, in the case of using a single-photon scheme, the laser light 101 of about 400 nm may be allowed to be incident, and the fluorescent light 108 of about 450 nm emitted from the sample 310 may be measured through the sensor 400. In this case, since the laser wavelength is close to the wavelength of the fluorescent light, it is required to appropriately select the laser removal filter 420. However, in the case of using a two-photon laser, the laser light 101 may have a wavelength of about 800 nm, and the fluorescent light 108 may have a wavelength of about 450 nm. The fluorescent light 108 based on a two-photon scheme may resolve filter issues by minimizing a difference between the wavelength of the laser light 101 and the wavelength of the fluorescent light 108, and may increase efficiency of PCR diagnosis.
The first lens 210, the second lens 410, the filter 420, and the sensor 400 may be configured in the same manner as illustrated in
Referring to
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The first laser light source 110 may be a reference laser light source. The first laser light source 110 may generate first laser light 102. The first laser light 102 may be reference light. According to an example, the first laser light source 110 may include a first optical fiber 111, a first pump light source 112, a first optical coupler 113, a volume Bragg grating 114, a semiconductor saturable absorber mirror 115.
The first optical fiber 111 may extend in one direction. The first optical fiber 111 may include a single-mode fiber. The first optical fiber 111 may include an optical fiber doped with a gain medium. Alternatively, the first optical fiber 111 may include a multi-mode optical fiber, but an embodiment of the inventive concept is not limited thereto.
The first pump light source 112 may provide first pump light to the first optical fiber 111 so as to oscillate the first laser light 102. The first pump light source 112 may include a light emitting diode. The first pump light may have a wavelength of about 976 nm.
The first optical coupler 113 may be connected to the first optical fiber 111. The first optical coupler 113 may connect the first pump light source 112 to the first optical fiber 111.
The volume Bragg grating 114 may be provided on one side end of the first optical fiber 111. The volume Bragg grating 114 may control a spectrum of the first laser light 102. A lens may be provided between the volume Bragg grating 114 and the first optical fiber 111. The lens may collimate the first laser light 102 on the volume Bragg grating 114.
The semiconductor saturable absorber mirror 115 may be connected to the other side of the first optical fiber 111. The semiconductor saturable absorber mirror 115 may reflect and/or resonate the first laser light 102. The semiconductor saturable absorber mirror 115 may pulse the first laser light 102. The first laser light 102 may be femto-second laser light generated by the semiconductor saturable absorber mirror 115.
The second laser light source 120 may be connected to the first laser light source 110. The second laser light source 120 may receive the first laser light 102 and generate second laser light 104. The second laser light 104 may have a longer wavelength than a wavelength of the first laser light 102. According to an example, the second laser light source 120 may include a second optical fiber 121, a second pump light source 122, a second optical coupler 123, a first nonlinear optical fiber 124, and a first wavelength tunable filter 125.
The second optical fiber 121 may be branched from the first optical fiber 111. The second optical fiber 121 may include an optical fiber doped with a gain medium.
The second pump light source 122 may be connected to the second optical fiber 121. The second pump light source 122 may provide second pump light in the second optical fiber 121 so as to obtain a gain of the second laser light 104. The second pump light may have a wavelength of about 980 nm.
The second optical coupler 123 may be connected to the second optical fiber 121. The second optical coupler 123 may connect the second pump light source 122 to the second optical fiber 121.
The first nonlinear optical fiber 124 may be connected to the second optical fiber 121 between the first optical fiber 111 and the second optical coupler 123. The first nonlinear optical fiber 124 may wavelength disperse the first laser light 102 and generate the second laser light 104. The second laser light 104 may have a longer wavelength than a wavelength of the first laser light 102.
An isolator 162 may be provided between the first nonlinear optical fiber 124 and the first optical fiber 111. The isolator 162 may prevent the second laser light 104 from being provided to the first optical fiber 111.
The first wavelength tunable filter 125 may be connected between the first nonlinear optical fiber 124 and the second optical coupler 123. The first wavelength tunable filter 125 may tune and/or adjust the wavelength of the second laser light 104.
The third laser light source 130 may be connected to the first optical fiber 111 of the first laser light source 110. The third laser light source 130 may generate third laser light 106. The third laser light 106 may have a shorter wavelength than the wavelengths of the first laser light 102 and the second laser light 104. According to an example, the third laser light source 130 may include a third optical fiber 131, a third pump light source 132, a third optical coupler 133, a second nonlinear optical fiber 134, and a second wavelength tunable filter 135.
The third optical fiber 131 may be connected to the first optical fiber 111. The third optical fiber 131 may be branched from the first optical fiber 111 and may be connected to a third output terminal 131a. The third optical fiber 131 may include a single-mode fiber. The third optical fiber 131 may include an optical fiber doped with a gain medium.
The third pump light source 132 may be connected to the third optical fiber 131. The third pump light source 132 may provide third pump light in the third optical fiber 131 so as to obtain a gain of the third laser light 106. The third pump light may have a wavelength of about 940 nm.
The third optical coupler 133 may be connected to the third optical fiber 131. The third optical coupler 133 may connect the third pump light source 132 to the third optical fiber 131.
The second nonlinear optical fiber 134 may be connected to the third optical fiber 131 between the first optical fiber 111 and the third optical coupler 133. The second nonlinear optical fiber 134 may wavelength disperse the first laser light 102 and generate the third laser light 106. The wavelength of the first laser light 102 may be shortened due to the second nonlinear optical fiber 134. That is, the third laser light 106 may have a shorter wavelength than the wavelength of the first laser light 102.
The isolator 162 may be provided between the second nonlinear optical fiber 134 and the first optical fiber 111. The isolator 162 may prevent the third laser light 106 from being provided to the first optical fiber 111.
The second wavelength tunable filter 135 may be provided between the second nonlinear optical fiber 134 and the third optical coupler 133. The second wavelength tunable filter 135 may tune and/or adjust the wavelength of the third laser light 106.
The optical modulator 200, the PCR chip 300, the sensor 400, and the code generator 500 may be configured in the same manner as illustrated in
Referring to
As described above, the PCR diagnosis apparatus according to an embodiment of the inventive concept may remove and/or minimize noise in fluorescent light using a code generator for switching laser light and fluorescent light through an orthogonal code.
Although the embodiments of the present invention have been described, it is understood that the present invention should not be limited to these embodiments but various changes and modifications can be made by one ordinary skilled in the art within the spirit and scope of the present invention as hereinafter claimed.
Number | Date | Country | Kind |
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10-2022-0071015 | Jun 2022 | KR | national |
This U.S. non-provisional patent application claims priority under 35 U.S.C. § 119 of Korean Patent Application No. 10-2022-0071015, filed on Jun. 10, 2022, the entire contents of which are hereby incorporated by reference.