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CN114894728A - Micro-fluidic chip and spectral information detection system - Google Patents

Micro-fluidic chip and spectral information detection system Download PDF

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CN114894728A
CN114894728A CN202210444135.1A CN202210444135A CN114894728A CN 114894728 A CN114894728 A CN 114894728A CN 202210444135 A CN202210444135 A CN 202210444135A CN 114894728 A CN114894728 A CN 114894728A
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李勤
李佳雨
胡晓明
魏泽文
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Abstract

The invention relates to the technical field of spectrum detection, and provides a micro-fluidic chip and a spectrum information detection system, wherein the micro-fluidic chip comprises: the chip comprises a transparent chip bottom plate, wherein a sample flow channel is formed on the chip bottom plate; a first groove is formed on the chip bottom plate and comprises a first cambered surface and a second cambered surface which are relatively sunken so as to construct an on-chip micro lens, the on-chip micro lens is positioned on the side surface of the sample flow channel, and the optical axis of the on-chip micro lens is vertical to the sample flow channel; and a second groove is formed on the chip bottom plate, the second groove is triangular so as to construct an on-chip prism, and the on-chip prism is positioned on one side of the on-chip micro lens, which is back to the sample flow channel. The micro-fluidic chip can obtain a spectrum consisting of monochromatic light with different wavelengths, is convenient for improving the subsequent detection precision, and has the characteristics of simple structure, small volume, low cost, portability, high stability and reliability, suitability for instant detection occasions and the like.

Description

微流控芯片及光谱信息检测系统Microfluidic chip and spectral information detection system

技术领域technical field

本发明涉及光谱检测技术领域,尤其涉及一种微流控芯片及光谱信息检测系统。The invention relates to the technical field of spectral detection, in particular to a microfluidic chip and a spectral information detection system.

背景技术Background technique

光谱检测广泛应用于细胞生物学、蛋白质工程、药物发现、医学诊断和生物技术等多个领域的研究中。目前的前沿生物学研究和临床医学研究,例如流式光谱检测,生化荧光检测以及化学发光现象研究等均可以通过检测多个荧光团的色散情况来分析不同生物样本的光谱信息。这种基于光谱的信号检测方法对于检测特定荧光团的信号非常有效。Spectroscopic detection is widely used in research in various fields such as cell biology, protein engineering, drug discovery, medical diagnosis, and biotechnology. Current frontier biological research and clinical medical research, such as flow spectroscopic detection, biochemical fluorescence detection and chemiluminescence phenomenon research, can analyze the spectral information of different biological samples by detecting the dispersion of multiple fluorophores. This spectral-based signal detection method is very efficient for detecting the signal of a specific fluorophore.

到目前为止,临床上可以针对光谱信号采集并分析的仪器,第一类是使用二向色镜和带通滤光片来选择特定的光谱带,以便使用光电倍增管(PMT)等点探测器进行检测,这类仪器的缺点是采集到的光谱信号分辨率低,并且不适合检测严重重叠的光谱信号;第二类是将散射光子通过附加的棱镜或光栅等片外光学元件发射到探测器中,从而可以测量完整的发射光谱,然而,这类器件往往结合复杂的光学透镜组合,需要多种附加的片外光学元件与光学系统相互配合,导致各元件之间远距离光学传播时会造成过多的能量损失,这不仅造成了检测精度低、设备体积过大、制作成本过高,同时需要专业人员进行操作,不适合即时检验(POCT)场合的应用。So far, the clinical instruments that can collect and analyze spectral signals, the first is the use of dichroic mirrors and bandpass filters to select specific spectral bands for the use of point detectors such as photomultiplier tubes (PMTs). The disadvantage of this type of instrument is that the collected spectral signal has low resolution and is not suitable for detecting severely overlapping spectral signals; the second type is to emit scattered photons to the detector through additional off-chip optical elements such as prisms or gratings However, such devices are often combined with complex optical lens combinations, requiring a variety of additional off-chip optical components and optical systems to cooperate with each other, resulting in long-distance optical propagation between components. Excessive energy loss not only results in low detection accuracy, excessive equipment volume, and high manufacturing cost, but also requires professionals to operate, which is not suitable for point-of-care inspection (POCT) applications.

发明内容SUMMARY OF THE INVENTION

本发明提供一种微流控芯片及光谱信息检测系统,通过在微流控芯片上一体集成样本流道、片上微透镜和片上棱镜,可以得到由不同波长的单色光组成的光谱,以便于后续可以同时检测具有高度重叠发射光谱的多个荧光团,获得较高的分辨率;并且可以降低光学信号的损失,提高检测精度,具有结构简单、体积小、成本低、便携化、稳定、可靠性高、适用于即时检测场合等特点。The invention provides a microfluidic chip and a spectral information detection system. By integrating a sample flow channel, an on-chip microlens and an on-chip prism on the microfluidic chip, spectra composed of monochromatic light of different wavelengths can be obtained, so as to facilitate the Subsequently, multiple fluorophores with highly overlapping emission spectra can be simultaneously detected to obtain higher resolution; and the loss of optical signals can be reduced, the detection accuracy can be improved, and it has the advantages of simple structure, small size, low cost, portability, stability and reliability. It has the characteristics of high performance and suitable for instant detection occasions.

本发明提供一种微流控芯片,包括:The present invention provides a microfluidic chip, comprising:

透明的芯片底板,所述芯片底板上形成有样本流道;a transparent chip base plate, on which a sample flow channel is formed;

所述芯片底板上形成有第一凹槽,所述第一凹槽包括两个相对凹陷的第一弧面和第二弧面,以构造出片上微透镜,所述片上微透镜位于所述样本流道的侧面,且所述片上微透镜的光轴垂直于所述样本流道,用于将所述样本流道内样本发出的发散光准直成复色平行光出射;A first groove is formed on the chip bottom plate, and the first groove includes two relatively concave first arc surfaces and second arc surfaces to construct an on-chip microlens, which is located in the sample. the side of the flow channel, and the optical axis of the on-chip microlens is perpendicular to the sample flow channel, for collimating the divergent light emitted by the sample in the sample flow channel into a polychromatic parallel light for output;

所述芯片底板上形成有第二凹槽,所述第二凹槽为三角形,以构造出片上棱镜,所述片上棱镜位于所述片上微透镜背向所述样本流道的一侧,用于将所述复色平行光色散成由不同波长的单色光组成的光谱并成像于所述芯片底板的边缘。A second groove is formed on the chip bottom plate, and the second groove is triangular to construct an on-chip prism, the on-chip prism is located on the side of the on-chip microlens facing away from the sample flow channel, and is used for The polychromatic parallel light is dispersed into a spectrum composed of monochromatic light of different wavelengths and imaged on the edge of the chip substrate.

根据本发明提供的一种微流控芯片,所述片上棱镜的光轴与所述片上微透镜的光轴重合。According to the microfluidic chip provided by the present invention, the optical axis of the on-chip prism coincides with the optical axis of the on-chip microlens.

根据本发明提供的一种微流控芯片,所述片上棱镜包括并排设置的第一片上棱镜和第二片上棱镜,所述第一片上棱镜位于所述片上微透镜与所述第二片上棱镜之间,所述第二片上棱镜位于所述第一片上棱镜与所述芯片底板的边缘之间。According to a microfluidic chip provided by the present invention, the on-chip prism includes a first on-chip prism and a second on-chip prism arranged side by side, and the first on-chip prism is located on the on-chip microlens and the second on-chip prism. Between the prisms, the second on-chip prism is located between the first on-chip prism and the edge of the chip bottom plate.

根据本发明提供的一种微流控芯片,所述样本流道内样本发出的发散光的发散角K满足:According to a microfluidic chip provided by the present invention, the divergence angle K of the divergent light emitted by the sample in the sample flow channel satisfies:

Figure BDA0003615137480000021
Figure BDA0003615137480000021

并且,

Figure BDA0003615137480000022
and,
Figure BDA0003615137480000022

K=2a;K=2a;

其中,a为发散光经过所述样本流道靠近所述片上微透镜的侧面时的入射角;n为所述芯片底板的介质材料折射率;b为发散光经过所述样本流道靠近所述片上微透镜的侧面时的折射角;n1为样本介质折射率;s1为所述第一弧面与所述样本流道靠近所述片上微透镜的侧面之间的最大距离;R1为所述第一弧面的曲率半径;g为发散光与所述第一弧面的相交点与所述第一弧面的曲率圆心的连线与光轴形成的夹角;l2为发散光与所述第一弧面的相交点至光轴的距离;s为样本与所述样本流道靠近所述片上微透镜的侧面之间的距离。Among them, a is the incident angle of the divergent light passing through the sample flow channel and approaching the side of the on-chip microlens; n is the refractive index of the dielectric material of the chip bottom plate; b is the divergent light passing through the sample flow channel and approaching the on-chip microlens. Refraction angle at the side of the on-chip microlens; n 1 is the refractive index of the sample medium; s 1 is the maximum distance between the first arc surface and the side of the sample flow channel close to the on-chip microlens; R 1 is The radius of curvature of the first arc surface; g is the angle formed between the intersection point of the diverging light and the first arc surface and the connecting line of the center of curvature of the first arc surface and the optical axis; l 2 is the diverging light The distance from the intersection point with the first arc surface to the optical axis; s is the distance between the sample and the side surface of the sample flow channel close to the on-chip microlens.

根据本发明提供的一种微流控芯片,所述芯片底板为玻璃材质时:According to a microfluidic chip provided by the present invention, when the chip bottom plate is made of glass material:

0.2mm≤R1≤3mm,0.2mm≤R2≤3mm;0.2mm≤R 1 ≤3mm, 0.2mm≤R 2 ≤3mm;

0.2mm≤s1≤5mm,0.2≤s2≤5mm,0.2≤s3≤5mm;0.2mm≤s 1 ≤5mm, 0.2≤s 2 ≤5mm, 0.2≤s 3 ≤5mm;

Figure BDA0003615137480000031
Figure BDA0003615137480000031

其中,R2为所述第二弧面的曲率半径;s2为所述第一弧面与所述第二弧面之间的最小距离;s3为所述第二弧面与所述第一片上棱镜的第一色散斜面与光轴交点之间的最大距离;l3为所述第二弧面的最高端点到光轴的距离。Wherein, R 2 is the radius of curvature of the second arc surface; s 2 is the minimum distance between the first arc surface and the second arc surface; s 3 is the second arc surface and the first arc surface The maximum distance between the intersection of the first dispersion slope of the upper prism and the optical axis; l3 is the distance from the highest end point of the second arc surface to the optical axis.

根据本发明提供的一种微流控芯片,不同波长的单色光成像于芯片底板边缘的色散位置与光轴的距离y满足:According to a microfluidic chip provided by the present invention, the distance y between the dispersion position and the optical axis of the monochromatic light of different wavelengths imaged on the edge of the chip base plate satisfies:

当μ<(γ+δ),y=(y3·tanδ+x4)·tan(δ-ρ)+y3When μ<(γ+δ), y=(y 3 ·tanδ+x 4 )·tan(δ-ρ)+y 3 ;

当μ>(γ+δ),y=(y3·tanδ+x4)·tan(δ+ρ)+y3When μ>(γ+δ), y=(y 3 ·tanδ+x 4 )·tan(δ+ρ)+y 3 ;

其中,μ为单色光经过所述第二片上棱镜的第三色散斜面时的折射角;γ为所述第二片上棱镜的第三色散斜面与垂直于光轴直线的夹角;δ为所述第二片上棱镜的第四色散斜面与垂直于光轴直线的夹角;y3为单色光与所述第二片上棱镜的第四色散斜面的相交点至光轴的距离;x4为所述第四色散斜面与光轴的交点至芯片底板的边缘面之间的距离;ρ为单色光经过所述第二片上棱镜的第四色散斜面时的折射角;Among them, μ is the refraction angle of the monochromatic light passing through the third dispersion slope of the prism on the second sheet; γ is the angle between the third dispersion slope of the prism on the second sheet and the line perpendicular to the optical axis; δ is the The angle between the 4th dispersion inclined plane of the prism on the second sheet and the straight line perpendicular to the optical axis; y is the distance from the intersection of the 4th dispersion inclined plane of the monochromatic light and the prism on the second sheet to the optical axis; x 4 is The distance between the intersection of the fourth dispersion slope and the optical axis to the edge surface of the chip base plate; ρ is the refraction angle of the monochromatic light when it passes through the fourth dispersion slope of the second upper prism;

并且所述光谱的色散展宽为:最小波长单色光的y值减去最大波长单色光的y值。And the dispersion broadening of the spectrum is: the y value of the minimum wavelength monochromatic light minus the y value of the maximum wavelength monochromatic light.

根据本发明提供的一种微流控芯片,所述芯片底板为玻璃材质时,所述光谱的色散展宽的范围为1~30毫米。According to a microfluidic chip provided by the present invention, when the chip bottom plate is made of glass material, the dispersion broadening range of the spectrum is 1-30 mm.

根据本发明提供的一种微流控芯片,所述芯片底板为玻璃材质时:According to a microfluidic chip provided by the present invention, when the chip bottom plate is made of glass material:

0.2mm≤s3≤5mm;0.2mm≤s 3 ≤5mm;

0°≤α≤40°;0°≤β≤45°;-70°≤γ≤5.7°;11°≤δ≤75°;0°≤α≤40°; 0°≤β≤45°; -70°≤γ≤5.7°; 11°≤δ≤75°;

0.1mm≤x1≤3mm;0.1mm≤x2≤3mm;0.1mm≤x 1 ≤3mm; 0.1mm≤x 2 ≤3mm;

0.1mm≤x3≤3mm;0.1mm≤x4≤30mm;0.1mm≤x 3 ≤3mm; 0.1mm≤x 4 ≤30mm;

其中,s3为所述第二弧面与所述第一片上棱镜的第一色散斜面与光轴交点之间的最大距离;α为所述第二弧面出射的复色平行光经过所述第一片上棱镜的第一色散斜面时的入射角或者所述第一片上棱镜的第一色散斜面与垂直于光轴直线的夹角;β为所述第一片上棱镜的第二色散斜面与垂直于光轴直线的夹角;x1为所述第一色散斜面与光轴的交点至所述第二色散斜面与光轴的交点的距离;x2为所述第二色散斜面与光轴的交点至所述第三色散斜面与光轴的交点的距离;x3为所述第三色散斜面与光轴的交点至所述第四色散斜面与光轴的交点的距离。Wherein, s 3 is the maximum distance between the second arc surface and the intersection of the first dispersion slope of the first upper prism and the optical axis; α is the polychromatic parallel light emitted by the second arc surface passing through the The incident angle of the first dispersive slope of the first on-chip prism or the angle between the first dispersive slope of the first on-chip prism and the straight line perpendicular to the optical axis; β is the second The angle between the dispersion slope and the straight line perpendicular to the optical axis; x 1 is the distance from the intersection of the first dispersion slope and the optical axis to the intersection of the second dispersion slope and the optical axis; x 2 is the second dispersion slope The distance from the intersection with the optical axis to the intersection of the third dispersion slope and the optical axis; x 3 is the distance from the intersection of the third dispersion slope and the optical axis to the intersection of the fourth dispersion slope and the optical axis.

根据本发明提供的一种微流控芯片,还包括透明的芯片顶盖,所述芯片顶盖密封设置于所述芯片底板上,且所述芯片顶盖设有进样孔和出样孔,所述进样孔和所述出样孔与所述样本流道的两端对应连通。A microfluidic chip provided according to the present invention further comprises a transparent chip top cover, the chip top cover is sealed on the chip bottom plate, and the chip top cover is provided with a sample inlet hole and a sample outlet hole, The sample injection hole and the sample outlet hole are in corresponding communication with both ends of the sample flow channel.

本发明还提供一种光谱信息检测系统,包括:光谱检测装置和上述的微流控芯片,所述光谱检测装置用于检测所述光谱。The present invention also provides a spectrum information detection system, comprising: a spectrum detection device and the above-mentioned microfluidic chip, wherein the spectrum detection device is used to detect the spectrum.

本发明提供的微流控芯片及光谱信息检测系统,通过在微流控芯片上一体集成样本流道、片上微透镜和片上棱镜,可以得到由不同波长的单色光组成的光谱,以便于后续可以通过光谱检测装置同时连续检测具有高度重叠发射光谱的多个荧光团,获得较高的分辨率;并且简化了光学元件模块,大大缩小了检测系统的体积,便于携带且降低生产成本,从而使基于该微流控芯片的光谱信息检测系统适用于各种即时检测的场合,针对不同的待测样本选择合适的制作材料并设计独特的芯片结构,有效地提高检测的稳定性和检测精度,提供多样化的临床信息;同时设计好的固定光学元件结构(片上微透镜和片上棱镜)保证了光学系统的精准度和检测的稳定性;本发明通过在一块芯片上集成片上微透镜和片上棱镜,可以针对不同应用设计最优位置,保证采集到更多的有效光学信号,降低光学信号的损失,提高检测精度。因此,本发明通过设计加工一体成型的微流控芯片,并将芯片与光谱检测装置结合,从而实现对待测样本的光谱信号检测,为微流控芯片应用于即时检测领域提供了一种创新性的方案,特别是对于临床感染性疾病、心血管疾病的光谱检测等具有重要的意义。The microfluidic chip and the spectral information detection system provided by the present invention can obtain the spectrum composed of monochromatic light of different wavelengths by integrating the sample flow channel, the on-chip microlens and the on-chip prism on the microfluidic chip, so as to facilitate the follow-up Multiple fluorophores with highly overlapping emission spectra can be simultaneously and continuously detected by the spectral detection device to obtain high resolution; and the optical component module is simplified, the volume of the detection system is greatly reduced, the portability is convenient and the production cost is reduced, so that the The spectral information detection system based on the microfluidic chip is suitable for various real-time detection occasions. For different samples to be tested, suitable materials are selected and a unique chip structure is designed, which can effectively improve the detection stability and detection accuracy. Diversified clinical information; at the same time, the designed fixed optical element structure (on-chip microlens and on-chip prism) ensures the accuracy of the optical system and the stability of detection; the present invention integrates the on-chip microlens and on-chip prism on a chip, The optimal position can be designed for different applications to ensure that more effective optical signals are collected, the loss of optical signals is reduced, and the detection accuracy is improved. Therefore, the present invention realizes the spectral signal detection of the sample to be tested by designing and processing an integrally formed microfluidic chip, and combining the chip with the spectral detection device, which provides an innovative method for the application of the microfluidic chip in the field of real-time detection. It is of great significance especially for the spectral detection of clinical infectious diseases and cardiovascular diseases.

本发明的附加方面和优点将在下面的描述中部分给出,部分将从下面的描述中变得明显,或通过本发明的实践了解到。Additional aspects and advantages of the present invention will be set forth, in part, from the following description, and in part will be apparent from the following description, or may be learned by practice of the invention.

附图说明Description of drawings

为了更清楚地说明本发明或相关技术中的技术方案,下面将对实施例或相关技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。In order to illustrate the technical solutions in the present invention or related technologies more clearly, the following briefly introduces the accompanying drawings required in the description of the embodiments or related technologies. Obviously, the drawings in the following description are some of the present invention. In the embodiments, for those of ordinary skill in the art, other drawings can also be obtained according to these drawings without any creative effort.

图1是本发明提供的芯片底板的结构示意图;1 is a schematic structural diagram of a chip base plate provided by the present invention;

图2是本发明提供的微流控芯片的结构示意图;2 is a schematic structural diagram of a microfluidic chip provided by the present invention;

图3是本发明提供的片上微透镜的光学路径示意图;3 is a schematic diagram of an optical path of an on-chip microlens provided by the present invention;

图4是本发明提供的片上棱镜的光学路径示意图;Fig. 4 is the optical path schematic diagram of the on-chip prism provided by the present invention;

图5是本发明提供的光谱信息检测系统的结构示意图;5 is a schematic structural diagram of a spectral information detection system provided by the present invention;

附图标记:Reference number:

100:微流控芯片;101:芯片底板;1001:样本流道;100: microfluidic chip; 101: chip bottom plate; 1001: sample flow channel;

1002:第一弧面;1003:第二弧面;1004:片上微透镜;1002: first arc surface; 1003: second arc surface; 1004: on-chip microlens;

1005:光轴;1006:第一片上棱镜;1007:第二片上棱镜;1005: Optical axis; 1006: Prism on the first sheet; 1007: Prism on the second sheet;

1008:第一色散斜面;1009:第二色散斜面;1008: the first dispersion slope; 1009: the second dispersion slope;

1010:第三色散斜面;1011:第四色散斜面;1012:边缘面;1010: the third dispersion slope; 1011: the fourth dispersion slope; 1012: the edge surface;

102:芯片顶盖;1021:进样孔;1022:出样孔;102: chip top cover; 1021: injection hole; 1022: sample outlet;

200:样本注射器;300:阵列光电探测器;400:上位机;200: sample syringe; 300: array photodetector; 400: upper computer;

500:收集桶;600:样本。500: collection bucket; 600: sample.

具体实施方式Detailed ways

为使本发明的目的、技术方案和优点更加清楚,下面将结合本发明中的附图,对本发明中的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。In order to make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention. , not all examples. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

在本发明实施例的描述中,需要说明的是,术语“中心”、“纵向”、“横向”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本发明实施例和简化描述,而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作,因此不能理解为对本发明实施例的限制。此外,术语“第一”、“第二”等仅用于描述目的,而不能理解为指示或暗示相对重要性。In the description of the embodiments of the present invention, it should be noted that the terms "center", "portrait", "horizontal", "top", "bottom", "front", "rear", "left", "right" , "vertical", "horizontal", "top", "bottom", "inside", "outside", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, only for the convenience of describing this Inventive embodiments and simplified descriptions are not intended to indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operate in a particular orientation, and therefore should not be construed as limiting the embodiments of the present invention. Furthermore, the terms "first," "second," etc. are used for descriptive purposes only and should not be construed to indicate or imply relative importance.

在本发明实施例的描述中,需要说明的是,除非另有明确的规定和限定,术语“相连”、“连接”应做广义理解,例如,可以是固定连接,也可以是可拆卸连接,或一体连接;可以是机械连接,也可以是电连接;可以是直接相连,也可以通过中间媒介间接相连。对于本领域的普通技术人员而言,可以具体情况理解上述术语在本发明实施例中的具体含义。In the description of the embodiments of the present invention, it should be noted that, unless otherwise expressly specified and limited, the terms "connected" and "connected" should be understood in a broad sense, for example, it may be a fixed connection or a detachable connection, Or integral connection; it can be mechanical connection or electrical connection; it can be directly connected or indirectly connected through an intermediate medium. Those of ordinary skill in the art can understand the specific meanings of the above terms in the embodiments of the present invention in specific situations.

在本发明实施例中,除非另有明确的规定和限定,第一特征在第二特征“上”或“下”可以是第一和第二特征直接接触,或第一和第二特征通过中间媒介间接接触。而且,第一特征在第二特征“之上”、“上方”和“上面”可是第一特征在第二特征正上方或斜上方,或仅仅表示第一特征水平高度高于第二特征。第一特征在第二特征“之下”、“下方”和“下面”可以是第一特征在第二特征正下方或斜下方,或仅仅表示第一特征水平高度小于第二特征。In the embodiments of the present invention, unless otherwise expressly specified and limited, the first feature "above" or "under" the second feature may be in direct contact with the first and second features, or the first and second features pass through the middle indirect contact with the media. Also, the first feature being "above", "over" and "above" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is level higher than the second feature. The first feature being "below", "below" and "below" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature has a lower level than the second feature.

在本说明书的描述中,参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明实施例的至少一个实施例或示例中。在本说明书中,对上述术语的示意性表述不必须针对的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或示例中以合适的方式结合。此外,在不相互矛盾的情况下,本领域的技术人员可以将本说明书中描述的不同实施例或示例以及不同实施例或示例的特征进行结合和组合。In the description of this specification, description with reference to the terms "one embodiment," "some embodiments," "example," "specific example," or "some examples", etc., mean specific features described in connection with the embodiment or example , structures, materials, or features are included in at least one example or example of embodiments of the present invention. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, those skilled in the art may combine and combine the different embodiments or examples described in this specification, as well as the features of the different embodiments or examples, without conflicting each other.

下面结合图1-图5描述本发明的微流控芯片及光谱信息检测系统。The microfluidic chip and the spectral information detection system of the present invention will be described below with reference to FIGS. 1 to 5 .

根据本发明第一方面的实施例,参照图1-图4所示,本发明提供的微流控芯片100,主要包括透明的芯片底板101,即芯片底板101采用透明材料制成,并且芯片底板101上形成有样本流道1001,样本流道1001可以实现样本600的装载与流动,起到约束样本600流动的作用,样本流道1001内为样本600,样本流道1001外部为芯片底板101材料介质,样本流道1001的特征尺寸可以与样本600的实际应用相匹配,例如样本流道1001的深宽比可以根据实际样本600测试要求进行设计。可以理解的是,本发明样本600的具体种类不做特别限制,只要可以产生光谱信号即可,例如可以为细胞、悬浮液等。According to the embodiment of the first aspect of the present invention, referring to FIGS. 1-4 , the microfluidic chip 100 provided by the present invention mainly includes a transparent chip base plate 101 , that is, the chip base plate 101 is made of a transparent material, and the chip base plate 101 is made of a transparent material. A sample flow channel 1001 is formed on the sample flow channel 101. The sample flow channel 1001 can realize the loading and flow of the sample 600 and play a role in restricting the flow of the sample 600. The sample flow channel 1001 is the sample 600, and the outside of the sample flow channel 1001 is the chip bottom plate 101 material. The medium, the characteristic size of the sample flow channel 1001 can be matched with the actual application of the sample 600 , for example, the aspect ratio of the sample flow channel 1001 can be designed according to the test requirements of the actual sample 600 . It can be understood that the specific type of the sample 600 of the present invention is not particularly limited, as long as it can generate a spectral signal, for example, it can be a cell, a suspension, and the like.

芯片底板101上形成有第一凹槽,第一凹槽包括两个相对凹陷的第一弧面1002和第二弧面1003,以构造出片上微透镜1004,即第一凹槽称为片上微透镜1004,第一弧面1002和第二弧面1003之间(即第一凹槽内部)可以为空气介质或其他符合光传输规律的其他介质,第一凹槽外部为芯片底板101材料介质;片上微透镜1004位于样本流道1001的侧面,且片上微透镜1004的光轴1005垂直于样本流道1001,用于将样本流道1001内样本600发出的发散光准直成复色平行光出射。A first groove is formed on the chip base plate 101, and the first groove includes two relatively concave first arc surfaces 1002 and second arc surfaces 1003 to construct an on-chip microlens 1004, that is, the first groove is called an on-chip microlens. The lens 1004, between the first arc surface 1002 and the second arc surface 1003 (that is, inside the first groove) can be an air medium or other medium that conforms to the law of light transmission, and the outside of the first groove is a material medium of the chip bottom plate 101; The on-chip microlens 1004 is located on the side of the sample flow channel 1001, and the optical axis 1005 of the on-chip microlens 1004 is perpendicular to the sample flow channel 1001, and is used for collimating the divergent light emitted by the sample 600 in the sample flow channel 1001 into a polychromatic parallel light output .

芯片底板101上形成有第二凹槽,第二凹槽为三角形,以构造出片上棱镜,即第二凹槽称为片上棱镜,第二凹槽内部可以为空气介质或符合光的色散原理的其他介质;第二凹槽外部为芯片底板101材料介质;片上棱镜位于片上微透镜1004背向样本流道1001的一侧,用于将片上微透镜1004准直形成的复色平行光色散成由不同波长的单色光组成的光谱,并且光谱成像于芯片底板101的边缘。A second groove is formed on the chip base plate 101, and the second groove is triangular to construct an on-chip prism, that is, the second groove is called an on-chip prism, and the inside of the second groove can be an air medium or a light-dispersion principle. Other medium; the outside of the second groove is the material medium of the chip bottom plate 101; the on-chip prism is located on the side of the on-chip microlens 1004 facing away from the sample flow channel 1001, and is used to disperse the polychromatic parallel light formed by the collimation of the on-chip microlens 1004 into Spectra composed of monochromatic light of different wavelengths, and the spectrum is imaged on the edge of the chip substrate 101 .

本发明实施例提供的微流控芯片100,通过在微流控芯片100上一体集成样本流道1001、片上微透镜1004和片上棱镜,可以得到由不同波长的单色光组成的光谱,以便于后续可以同时检测具有高度重叠发射光谱的多个荧光团,获得较高的分辨率;并且可以降低光学信号的损失,提高检测精度,具有结构简单、体积小、成本低、便携化、稳定可靠性高、适用于各种即时检测场合等特点,对于临床感染性疾病、心血管疾病的光谱检测等具有重要的意义。In the microfluidic chip 100 provided by the embodiment of the present invention, by integrally integrating the sample flow channel 1001, the on-chip microlens 1004 and the on-chip prism on the microfluidic chip 100, a spectrum composed of monochromatic light of different wavelengths can be obtained, so as to facilitate the Subsequently, multiple fluorophores with highly overlapping emission spectra can be simultaneously detected to obtain higher resolution; and the loss of optical signals can be reduced, the detection accuracy can be improved, and it has the advantages of simple structure, small size, low cost, portability, and stable reliability. It is of great significance for the spectral detection of clinical infectious diseases and cardiovascular diseases, etc.

根据本发明的一个实施例,如图2所示,本发明微流控芯片100还包括透明的芯片顶盖102,即芯片顶盖102采用透明材料制成,芯片顶盖102密封设置于芯片底板101上,且芯片顶盖102设有进样孔1021和出样孔1022,进样孔1021和出样孔1022均为贯穿孔且分别与样本流道1001的两端对应连通。样本600通过进样孔1021进入样本流道1001发出发散光,依次通过片上微透镜1004准直和片上棱镜色散成光谱,然后通过出样孔1022流出。According to an embodiment of the present invention, as shown in FIG. 2 , the microfluidic chip 100 of the present invention further includes a transparent chip top cover 102 , that is, the chip top cover 102 is made of a transparent material, and the chip top cover 102 is sealed and disposed on the chip bottom plate 101 , and the chip top cover 102 is provided with a sample injection hole 1021 and a sample outlet hole 1022 . The sample 600 enters the sample flow channel 1001 through the sample injection hole 1021 and emits divergent light, which is collimated by the on-chip microlens 1004 and dispersed into a spectrum by the on-chip prism in turn, and then flows out through the sample outlet hole 1022 .

在本示例中,样本流道1001、片上微透镜1004和片上棱镜均集成形成于芯片底板101的上表面,芯片顶盖102密封叠放于芯片底板101的上表面,并且进样孔1021和出样孔1022分别与样本流道1001的两端对齐。In this example, the sample flow channel 1001 , the on-chip microlens 1004 and the on-chip prism are all integrally formed on the upper surface of the chip base plate 101 , the chip top cover 102 is sealed and stacked on the upper surface of the chip base plate 101 , and the sample injection holes 1021 and the outlet The sample holes 1022 are respectively aligned with both ends of the sample flow channel 1001 .

本发明微流控芯片100的具体材料不做特别限制,可以采用光学性能优良的透明材料(例如石英、玻璃、PDMS、PMMA、SU-8光刻胶等)加工制作芯片底板101和芯片顶盖102。The specific materials of the microfluidic chip 100 of the present invention are not particularly limited, and transparent materials with excellent optical properties (such as quartz, glass, PDMS, PMMA, SU-8 photoresist, etc.) can be used to process the chip bottom plate 101 and the chip top cover. 102.

根据本发明的一个实施例,样本流道1001的宽度为100微米,深度为200微米,样本600与样本流道1001靠近片上微透镜1004的侧面之间的距离为s,要求s≤100μm。According to an embodiment of the present invention, the sample flow channel 1001 has a width of 100 microns and a depth of 200 microns.

根据本发明的一个实施例,如图1所示,片上棱镜的光轴1005与片上微透镜1004的光轴1005重合,有利于微小结构的设计和加工,保证片上光学传播过程的准确和稳定,降低背景光或材料介质引入的误差干扰,从而可以提高色散效果,改善光谱检测的精确度。According to an embodiment of the present invention, as shown in FIG. 1 , the optical axis 1005 of the on-chip prism coincides with the optical axis 1005 of the on-chip microlens 1004, which is beneficial to the design and processing of microstructures, and ensures the accuracy and stability of the on-chip optical propagation process. Reduce the error interference introduced by background light or material medium, so that the dispersion effect can be improved and the accuracy of spectral detection can be improved.

根据本发明的一个实施例,如图1和图4所示,片上棱镜包括并排设置的第一片上棱镜1006和第二片上棱镜1007,第一片上棱镜1006位于片上微透镜1004与第二片上棱镜1007之间,第二片上棱镜1007位于第一片上棱镜1006与芯片底板101的边缘之间。具体地,第一片上棱镜1006具有两个色散斜面,分别为第一色散斜面1008和第二色散斜面1009;第二片上棱镜1007具有两个色散斜面,分别为第三色散斜面1010和第四色散斜面1011;并且第一片上棱镜1006和第二片上棱镜1007的光轴1005均与片上微透镜1004的光轴1005重合;每个片上棱镜的两个色散斜面之间为空气介质。According to an embodiment of the present invention, as shown in FIG. 1 and FIG. 4 , the on-chip prism includes a first on-chip prism 1006 and a second on-chip prism 1007 arranged side by side, and the first on-chip prism 1006 is located between the on-chip microlens 1004 and the second on-chip prism 1007 . Between the on-chip prisms 1007 , the second on-chip prism 1007 is located between the first on-chip prism 1006 and the edge of the chip substrate 101 . Specifically, the first on-chip prism 1006 has two dispersion slopes, which are the first dispersion slope 1008 and the second dispersion slope 1009 respectively; the second on-chip prism 1007 has two dispersion slopes, which are the third dispersion slope 1010 and the fourth dispersion slope respectively. Dispersion slope 1011; and the optical axes 1005 of the first on-chip prism 1006 and the second on-chip prism 1007 coincide with the optical axis 1005 of the on-chip microlens 1004; the air medium is between the two dispersive slopes of each on-chip prism.

可以理解的是,本发明片上棱镜的具体数量不做特别限制,可根据实际设计需求进行调整。It can be understood that the specific number of on-chip prisms in the present invention is not particularly limited, and can be adjusted according to actual design requirements.

由于本发明片上微透镜1004主要用于将样本600发出的发散光准直成复色平行光出射,因此,为了采集到合适的发散光信号,需要针对样本600发出的发散光的发散角K进行计算,选择合适的设计参数,可以有效提高检测的稳定性和检测精度。Since the on-chip microlens 1004 of the present invention is mainly used to collimate the divergent light emitted by the sample 600 into a polychromatic parallel light for output, therefore, in order to collect a suitable divergent light signal, it is necessary to measure the divergence angle K of the divergent light emitted by the sample 600 . Calculation and selection of appropriate design parameters can effectively improve detection stability and detection accuracy.

根据本发明的一个实施例,如图3所示,其中,片上微透镜1004的第一弧面1002的曲率圆心为点O,片上微透镜1004的第二弧面1003的曲率圆心为点O′,a为发散光经过样本流道1001靠近片上微透镜1004的侧面时的入射角;n为芯片底板101的介质材料折射率;b为发散光经过样本流道1001靠近片上微透镜1004的侧面时的折射角;n1为样本600介质折射率;s1为第一弧面1002与样本流道1001靠近片上微透镜1004的侧面之间的最大距离;R1为第一弧面1002的曲率半径;g为发散光与第一弧面1002的相交点B与第一弧面1002的曲率圆心O的连线与光轴1005形成的夹角;l2为发散光与第一弧面1002的相交点B至光轴1005的距离;s为样本600与样本流道1001靠近片上微透镜1004的侧面之间的距离;R2为第二弧面1003的曲率半径;s2为第一弧面1002与第二弧面1003之间的最小距离;s3为第二弧面1003与第一片上棱镜1006的第一色散斜面1008与光轴1005交点之间的最大距离;l3为第二弧面1003的最高端点C到光轴的距离。According to an embodiment of the present invention, as shown in FIG. 3 , the center of curvature of the first arc surface 1002 of the on-chip microlens 1004 is point O, and the center of curvature of the second arc surface 1003 of the on-chip microlens 1004 is point O' , a is the incident angle when the divergent light passes through the sample flow channel 1001 and is close to the side of the on-chip microlens 1004; n is the refractive index of the dielectric material of the chip base plate 101; n 1 is the refractive index of the medium of the sample 600; s 1 is the maximum distance between the first arc surface 1002 and the side surface of the sample flow channel 1001 close to the on-chip microlens 1004; R 1 is the radius of curvature of the first arc surface 1002 g is the angle formed by the line of intersection B of the divergent light and the first arc surface 1002 and the center of curvature O of the first arc surface 1002 and the optical axis 1005; l 2 is the intersection of the diverging light and the first arc surface 1002 The distance from point B to the optical axis 1005; s is the distance between the sample 600 and the side surface of the sample flow channel 1001 close to the on-chip microlens 1004; R 2 is the radius of curvature of the second arc surface 1003; s 2 is the first arc surface 1002 The minimum distance between the second arc surface 1003 and the second arc surface 1003; s 3 is the maximum distance between the intersection point between the second arc surface 1003 and the first dispersion slope 1008 of the prism 1006 on the first sheet and the optical axis 1005; l 3 is the second arc The distance from the highest end point C of the surface 1003 to the optical axis.

并且,第一弧面1002与第二弧面1003之间的空气介质折射率为1,平行入射第一片上棱镜1006的第一色散斜面1008的光线在经过片上微透镜1004第二弧面1003的最高端点C时,入射角为e,折射角为f;光线在经过片上微透镜1004的第一弧面1002时,入射角为c,折射角为d,光线与样本流道1001侧面相交于点A,点A到光轴1005的垂直距离设置为l1In addition, the refractive index of the air medium between the first arc surface 1002 and the second arc surface 1003 is 1, and the light parallel to the first dispersive slope 1008 of the first on-chip prism 1006 passes through the second arc surface 1003 of the on-chip microlens 1004 When the highest end point C of , the incident angle is e, and the refraction angle is f; when the light passes through the first arc surface 1002 of the on-chip microlens 1004, the incident angle is c, and the refraction angle is d, and the light intersects the side of the sample flow channel 1001 at Point A, the vertical distance from point A to the optical axis 1005 is set to l 1 .

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Figure BDA0003615137480000112
Figure BDA0003615137480000112

通过变换可以求得l2与g;l 2 and g can be obtained by transformation;

再令order again

d=g+f-e; (5)d=g+f-e; (5)

Figure BDA0003615137480000113
Figure BDA0003615137480000113

b=g-c; (7)b=g-c; (7)

得到get

Figure BDA0003615137480000114
Figure BDA0003615137480000114

并且同时有and also have

Figure BDA0003615137480000115
Figure BDA0003615137480000115

通过调整自变量R1,R2,s1,s2,l3的值,根据公式(8)和公式(9)可以获得合适的因变量a,从而满足实际检测过程中对样本600发出的发散光的发散角K=2a的要求,进而采集到合适的发散光信号。By adjusting the values of the independent variables R 1 , R 2 , s 1 , s 2 , and l 3 , a suitable dependent variable a can be obtained according to formula (8) and formula (9), so as to satisfy the requirements of the sample 600 issued in the actual detection process. The divergence angle K=2a of divergent light is required, and then a suitable divergent light signal is collected.

根据本发明的一个实施例,芯片底板101为玻璃材质时:According to an embodiment of the present invention, when the chip bottom plate 101 is made of glass:

0.2mm≤R1≤3mm,0.2mm≤R2≤3mm;0.2mm≤R 1 ≤3mm, 0.2mm≤R 2 ≤3mm;

0.2mm≤s1≤5mm,0.2≤s2≤5mm,0.2≤s3≤5mm;0.2mm≤s 1 ≤5mm, 0.2≤s 2 ≤5mm, 0.2≤s 3 ≤5mm;

Figure BDA0003615137480000116
Figure BDA0003615137480000116

本发明实施例通过上述参数设计,可以在保证整个芯片小体积的前提下,获得较高分辨率的光谱信息,有利于同时检测具有高度重叠发射光谱的多个荧光团。Through the above parameter design, the embodiment of the present invention can obtain spectral information with higher resolution on the premise of ensuring the small volume of the entire chip, which is conducive to the simultaneous detection of multiple fluorophores with highly overlapping emission spectra.

由于本发明片上棱镜主要用于将片上微透镜1004准直形成的复色平行光色散成由不同波长的单色光组成的光谱信息,并成像在微流控芯片100的边缘。为了获得符合光谱检测装置检测要求的色散展宽,需要针对不同波长的单色光的色散位置进行计算,选择合适的设计参数,有利于提高检测精度。Because the on-chip prism of the present invention is mainly used to disperse the polychromatic parallel light formed by the collimation of the on-chip microlens 1004 into spectral information composed of monochromatic light of different wavelengths, and image the edge of the microfluidic chip 100 . In order to obtain the dispersion broadening that meets the detection requirements of the spectral detection device, it is necessary to calculate the dispersion position of monochromatic light of different wavelengths, and select appropriate design parameters, which is beneficial to improve the detection accuracy.

根据本发明的一个实施例,如图4所示,其中,μ为单色光经过第二片上棱镜1007的第三色散斜面1010时的折射角;γ为第二片上棱镜1007的第三色散斜面1010与垂直于光轴1005直线的夹角;δ为第二片上棱镜1007的第四色散斜面1011与垂直于光轴1005直线的夹角;y3为单色光与第二片上棱镜1007的第四色散斜面1011的相交点F至光轴1005的距离;x4为第四散斜面1011与光轴1005的交点至芯片底板101的边缘面1012之间的距离;ρ为单色光经过第二片上棱镜1007的第四色散斜面1011时的折射角;y为不同波长的单色光成像于芯片底板101边缘的色散位置与光轴1005的距离。According to an embodiment of the present invention, as shown in FIG. 4 , where μ is the refraction angle of the monochromatic light passing through the third dispersion slope 1010 of the second upper prism 1007 ; γ is the third dispersion slope of the second upper prism 1007 The angle between 1010 and the line perpendicular to the optical axis 1005; δ is the angle between the fourth dispersion slope 1011 of the prism 1007 on the second sheet and the straight line perpendicular to the optical axis 1005; y 3 is the angle between the monochromatic light and the prism 1007 on the second sheet The distance from the intersection point F of the four dispersion slopes 1011 to the optical axis 1005; x 4 is the distance from the intersection of the fourth dispersion slope 1011 and the optical axis 1005 to the edge surface 1012 of the chip bottom plate 101; ρ is the distance between the monochromatic light passing through the second Refraction angle of the fourth dispersion slope 1011 of the on-chip prism 1007; y is the distance between the dispersion position and the optical axis 1005 of the monochromatic light of different wavelengths imaged on the edge of the chip substrate 101 .

并且,第一色散斜面1008与第二色散斜面1009之间以及第三色散斜面1010与第四色散斜面1011之间的空气介质折射率为1;s3为第二弧面1003与第一片上棱镜1006的第一色散斜面1008与光轴1005交点之间的最大距离;α为第二弧面1003出射的复色平行光经过第一片上棱镜1006的第一色散斜面1008时的入射角或者第一片上棱镜1006的第一色散斜面1008与垂直于光轴1005直线的夹角,即两个角度数值是相等的,ε为第二弧面1003出射的复色平行光经过第一片上棱镜1006的第一色散斜面1008时的折射角,光线经过第一片上棱镜1006的第二色散斜面1009时的入射角为∈,折射角为θ,并且折射光线与第二色散斜面1009相交于点D,点D到光轴1005的垂直距离为y1;光线经过第二片上棱镜1007的第三色散斜面1010时的入射角为

Figure BDA0003615137480000121
折射角为μ,并且折射光线与第三色散斜面1010相交于点E,点E到光轴1005的距离为y2;折射光线经过第二片上棱镜1007的第四色散斜面1011时的入射角为π,折射角为ρ;β为第一片上棱镜1006的第二色散斜面1009与垂直于光轴1005直线的夹角;折射光线到达微流控芯片100的边缘面1012时相交于点G,点G与光轴1005之间的距离为y;x1为第一色散斜面1008与光轴1005的交点至第二色散斜面1009与光轴1005的交点的距离;x2为第二色散斜面1009与光轴1005的交点至第三色散斜面1010与光轴1005的交点的距离;x3为第三色散斜面1010与光轴1005的交点至第四色散斜面1011与光轴1005的交点的距离。可以理解的是,图4中仅示出一条单色光进行示例说明,其他单色光同理。In addition, the refractive index of the air medium between the first dispersion slope 1008 and the second dispersion slope 1009 and between the third dispersion slope 1010 and the fourth dispersion slope 1011 is 1; s 3 is the second arc surface 1003 and the first surface The maximum distance between the intersection of the first dispersion slope 1008 of the prism 1006 and the optical axis 1005; α is the incident angle of the polychromatic parallel light emitted by the second arc surface 1003 passing through the first dispersion slope 1008 of the prism 1006 on the first sheet or The angle between the first dispersive slope 1008 of the prism 1006 on the first sheet and the straight line perpendicular to the optical axis 1005, that is, the two angle values are equal, and ε is the polychromatic parallel light emitted by the second arc surface 1003 passing through the first sheet. The refraction angle of the first dispersion slope 1008 of the prism 1006, the incident angle of the light passing through the second dispersion slope 1009 of the first on-chip prism 1006 is ∈, the refraction angle is θ, and the refracted light intersects the second dispersion slope 1009 at Point D, the vertical distance from point D to the optical axis 1005 is y 1 ; the incident angle of the light passing through the third dispersion slope 1010 of the second prism 1007 is
Figure BDA0003615137480000121
The refraction angle is μ, and the refracted ray intersects the third dispersive slope 1010 at point E, and the distance from point E to the optical axis 1005 is y 2 ; the incident angle of the refracted ray passing through the fourth dispersive slope 1011 of the second prism 1007 is π, the refraction angle is ρ; β is the included angle between the second dispersion slope 1009 of the prism 1006 on the first sheet and the straight line perpendicular to the optical axis 1005; the refracted light intersects at point G when it reaches the edge surface 1012 of the microfluidic chip 100, The distance between point G and the optical axis 1005 is y; x 1 is the distance from the intersection of the first dispersion slope 1008 and the optical axis 1005 to the intersection of the second dispersion slope 1009 and the optical axis 1005 ; x 2 is the second dispersion slope 1009 The distance from the intersection with the optical axis 1005 to the intersection of the third dispersion slope 1010 and the optical axis 1005 ; x 3 is the distance from the intersection of the third dispersion slope 1010 and the optical axis 1005 to the intersection of the fourth dispersion slope 1011 and the optical axis 1005 . It can be understood that only one piece of monochromatic light is shown in FIG. 4 for illustration, and the same is true for other monochromatic lights.

Have

ε=arcsin(n·sinα); (10)ε=arcsin(n·sinα); (10)

当ε<(α+β)When ε<(α+β)

∈=α+β-ε; (11)∈=α+β-ε; (11)

Figure BDA0003615137480000131
Figure BDA0003615137480000131

Figure BDA0003615137480000132
Figure BDA0003615137480000132

Figure BDA0003615137480000136
Figure BDA0003615137480000136

Figure BDA0003615137480000137
Figure BDA0003615137480000137

Figure BDA0003615137480000133
Figure BDA0003615137480000133

当ε>(α+β)When ε>(α+β)

∈=ε-α-β; (17)∈=ε-α-β; (17)

Figure BDA0003615137480000134
Figure BDA0003615137480000134

Figure BDA0003615137480000135
Figure BDA0003615137480000135

Figure BDA0003615137480000138
Figure BDA0003615137480000138

Figure BDA0003615137480000139
Figure BDA0003615137480000139

Figure BDA0003615137480000141
Figure BDA0003615137480000141

当μ<(γ+δ)When μ<(γ+δ)

π=γ+δ-μ; (23)π=γ+δ-μ; (23)

Figure BDA0003615137480000142
Figure BDA0003615137480000142

Figure BDA0003615137480000143
Figure BDA0003615137480000143

y=(y3·tanδ+x4)·tan(δ-ρ)+y3; (26)y=(y 3 ·tanδ+x 4 )·tan(δ-ρ)+y 3 ; (26)

当μ>(γ+δ)When μ>(γ+δ)

π= μ-γ-δ; (27)π = μ-γ-δ; (27)

Figure BDA0003615137480000144
Figure BDA0003615137480000144

Figure BDA0003615137480000145
Figure BDA0003615137480000145

y=(y3·tanδ+x4)·tan(δ+ρ)+y3; (30)y=(y 3 ·tanδ+x 4 )·tan(δ+ρ)+y 3 ; (30)

通过设计合适的自变量α,β,γ,δ,x1,x2,x3,x4,根据公式(26)和公式(30),可以计算不同波长光线在微流控芯片边缘面1012相应的色散位置与光轴1005之间的距离y;并通过将最小波长单色光计算得到的y值减去最大波长单色光计算得到的y值,可以得到合适的光谱色散展宽。By designing appropriate independent variables α, β, γ, δ, x 1 , x 2 , x 3 , x 4 , according to formula (26) and formula (30), it is possible to calculate the edge surface 1012 of the microfluidic chip for light with different wavelengths The distance y between the corresponding dispersion position and the optical axis 1005; and the appropriate spectral dispersion broadening can be obtained by subtracting the y value calculated by the minimum wavelength monochromatic light from the y value calculated by the maximum wavelength monochromatic light.

根据本发明的一个实施例,芯片底板101为玻璃材质时,光谱色散展宽的范围为1~30毫米,可以提高色散效果,有利于提高光谱的检测精度。According to an embodiment of the present invention, when the chip base plate 101 is made of glass, the spectral dispersion broadening range is 1-30 mm, which can improve the dispersion effect and improve the detection accuracy of the spectrum.

根据本发明的一个实施例,芯片底板101为玻璃材质时:According to an embodiment of the present invention, when the chip bottom plate 101 is made of glass:

0.2mm≤s3≤5mm;0.2mm≤s 3 ≤5mm;

0°≤α≤40°;0°≤β≤45°;-70°≤γ≤5.7°;11°≤δ≤75°;0°≤α≤40°; 0°≤β≤45°; -70°≤γ≤5.7°; 11°≤δ≤75°;

0.1mm≤x1≤3mm;0.1mm≤x2≤3mm;0.1mm≤x 1 ≤3mm; 0.1mm≤x 2 ≤3mm;

0.1mm≤x3≤3mm;0.1mm≤x4≤30mm。 0.1mm≤x3≤3mm ; 0.1mm≤x4≤30mm .

本发明实施例通过上述参数设计,可以保证整个芯片的体积较小,并且可以获得较高分辨率的光谱信息,有利于提高检测精度。Through the above parameter design in the embodiment of the present invention, the volume of the entire chip can be ensured to be small, and spectral information with higher resolution can be obtained, which is beneficial to improve the detection accuracy.

根据本发明第二方面的实施例,本发明还提供一种光谱信息检测系统,包括:光谱检测装置和上述实施例的微流控芯片100,光谱检测装置用于检测成像于微流控芯片100上的光谱信号。According to an embodiment of the second aspect of the present invention, the present invention further provides a spectral information detection system, comprising: a spectral detection device and the microfluidic chip 100 of the above-mentioned embodiment, the spectral detection device is used for detecting and imaging on the microfluidic chip 100 on the spectral signal.

本发明光谱检测装置的具体类型不做特别限制,例如可以对各种样本进行光谱信号检测的分析,包括但不限于对样本的散射光谱、荧光光谱、化学发光等光谱信号的分析。The specific type of the spectral detection device of the present invention is not particularly limited, for example, various samples can be analyzed for spectral signal detection, including but not limited to the analysis of spectral signals such as scattering spectra, fluorescence spectra, and chemiluminescence of the samples.

根据本发明的一个实施例,如图5所示,光谱检测装置包括阵列光电探测器300和上位机400,阵列光电探测器300搭载于微流控芯片100的边缘位置,实现光谱信号的连续检测采集,上位机400与阵列光电探测器300相连,用于对光谱信息进行分析。According to an embodiment of the present invention, as shown in FIG. 5 , the spectral detection device includes an array photodetector 300 and a host computer 400. The array photodetector 300 is mounted on the edge of the microfluidic chip 100 to realize continuous detection of spectral signals For acquisition, the host computer 400 is connected to the array photodetector 300 for analyzing the spectral information.

根据本发明的一个实施例,光谱信息检测系统还包括样本注射器200和收集桶500,样本注射器200通过导管与芯片顶盖102的进样孔1021相连,用于将样本600从进样孔1021注入样本流道1001;收集桶500通过导管与芯片顶盖102的出样孔1022相连,检测后的样本600可以经出样孔1022流入收集桶500内收集。According to an embodiment of the present invention, the spectral information detection system further includes a sample injector 200 and a collection barrel 500. The sample injector 200 is connected to the injection hole 1021 of the chip top cover 102 through a conduit for injecting the sample 600 from the injection hole 1021. The sample flow channel 1001; the collection bucket 500 is connected to the sample outlet hole 1022 of the chip top cover 102 through a conduit, and the detected sample 600 can flow into the collection bucket 500 through the sample outlet hole 1022 for collection.

下面结合一个具体示例对本发明提供的光谱信息检测系统的工作原理进行描述,大致包括:The working principle of the spectral information detection system provided by the present invention is described below with reference to a specific example, which roughly includes:

通过样本注射器200将悬浮液样本从进样孔1021注入样本流道1001,当悬浮液样本流过样本流道1001与光轴1005相交的特定检测位置时,含有光谱信号的悬浮液样本会发出不同波长的光谱信号,并以一定发散角出射;发散光通过片上微透镜1004准直成复色平行光进入片上棱镜,此处可根据需要设计一个或多个片上棱镜从而获得最佳的光谱展宽效果。在片上棱镜的色散作用下,不同波长的光信号以不同角度出射到微流控芯片100边缘,形成满足阵列光电探测器300要求的色散展宽;然后由阵列光电探测器300检测采集相应的光谱信息,并传输到上位机400呈现出光谱信号,从而进行悬浮液样本的光谱信息分析;悬浮液样本最终从出样孔1022流出,由收集桶500收集。The suspension sample is injected from the injection hole 1021 into the sample flow channel 1001 through the sample injector 200. When the suspension sample flows through the specific detection position where the sample flow channel 1001 intersects the optical axis 1005, the suspension sample containing spectral signals will emit different The spectral signal of the wavelength is emitted at a certain divergence angle; the divergent light is collimated by the on-chip microlens 1004 into a polychromatic parallel light and enters the on-chip prism. Here, one or more on-chip prisms can be designed as required to obtain the best spectral broadening effect. . Under the dispersion effect of the on-chip prism, optical signals of different wavelengths are emitted to the edge of the microfluidic chip 100 at different angles to form dispersion broadening that meets the requirements of the array photodetector 300; then the array photodetector 300 detects and collects corresponding spectral information , and transmitted to the host computer 400 to present the spectral signal, so as to analyze the spectral information of the suspension sample;

最后应说明的是:以上实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, but not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that it can still be The technical solutions described in the foregoing embodiments are modified, or some technical features thereof are equivalently replaced; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. A microfluidic chip, comprising:
a transparent chip base plate, wherein a sample flow channel is formed on the chip base plate;
a first groove is formed in the chip bottom plate, the first groove comprises a first arc surface and a second arc surface which are relatively recessed so as to construct an on-chip micro lens, the on-chip micro lens is located on the side surface of the sample flow channel, and the optical axis of the on-chip micro lens is perpendicular to the sample flow channel and is used for collimating divergent light emitted by a sample in the sample flow channel into polychromatic parallel light to be emitted;
the chip bottom plate is formed with a second groove, the second groove is triangular to construct an on-chip prism, the on-chip prism is located on one side of the on-chip micro lens, which faces away from the sample flow channel, and is used for dispersing the compound color parallel light into a spectrum composed of monochromatic light with different wavelengths and imaging the spectrum on the edge of the chip bottom plate.
2. The microfluidic chip of claim 1, wherein an optical axis of the on-chip prism coincides with an optical axis of the on-chip microlens.
3. The microfluidic chip according to claim 2, wherein the on-chip prisms include a first on-chip prism and a second on-chip prism arranged side by side, the first on-chip prism being located between the on-chip micro-lens and the second on-chip prism, the second on-chip prism being located between the first on-chip prism and an edge of the chip base plate.
4. The microfluidic chip according to claim 3, wherein the divergent angle K of the divergent light emitted by the sample in the sample channel satisfies the following condition:
Figure FDA0003615137470000011
and the number of the first and second electrodes,
Figure FDA0003615137470000012
K=2a;
wherein a is an incident angle when divergent light passes through the side surface of the sample flow channel close to the on-chip micro lens; n is the refractive index of the dielectric material of the chip bottom plate;b is the refraction angle of the divergent light passing through the side surface of the sample flow channel close to the on-chip micro lens; n is 1 Is the sample medium refractive index; s 1 The maximum distance between the first cambered surface and the side surface of the sample flow channel close to the on-chip micro lens is set; r 1 The curvature radius of the first cambered surface; g is an included angle formed by a connecting line of an intersection point of the divergent light and the first cambered surface and a curvature circle center of the first cambered surface and an optical axis; l 2 The distance from the intersection point of the divergent light and the first cambered surface to the optical axis; and s is the distance between the sample and the side surface of the sample flow channel close to the on-chip micro lens.
5. The microfluidic chip according to claim 4, wherein when the chip bottom plate is made of glass:
0.2mm≤R 1 ≤3mm,0.2mm≤R 2 ≤3mm;
0.2mm≤s 1 ≤5mm,0.2≤s 2 ≤5mm,0.2≤s 3 ≤5mm;
Figure FDA0003615137470000021
wherein R is 2 The radius of curvature of the second cambered surface; s 2 Is the minimum distance between the first cambered surface and the second cambered surface; s 3 The maximum distance between the second cambered surface and the intersection point of the first dispersion inclined plane and the optical axis of the first upper prism is set; l 3 The distance from the highest end point of the second cambered surface to the optical axis.
6. The microfluidic chip according to claim 3, wherein the distance y between the dispersion position of monochromatic light with different wavelengths imaged on the edge of the chip bottom plate and the optical axis satisfies:
when mu is<(γ+δ),y=(y 3 ·tanδ+x 4 )·tan(δ-ρ)+y 3
When mu is>(γ+δ),y=(y 3 ·tanδ+x 4 )·tan(δ+ρ)+y 3
Mu is a refraction angle when monochromatic light passes through the third color dispersion inclined plane of the second on-chip prism; gamma is an included angle between the third astigmatism inclined plane of the second on-chip prism and a straight line vertical to the optical axis; delta is an included angle between a fourth dispersion inclined plane of the second on-chip prism and a straight line vertical to the optical axis; y is 3 The distance from the intersection point of the monochromatic light and the fourth dispersion inclined plane of the second on-chip prism to the optical axis; x is the number of 4 The distance from the intersection point of the fourth dispersion slope and the optical axis to the edge surface of the chip bottom plate is obtained; rho is a refraction angle of the monochromatic light when the monochromatic light passes through the fourth dispersion slope of the second on-chip prism;
and the dispersion spread of the spectrum is: the y value of the minimum wavelength monochromatic light minus the y value of the maximum wavelength monochromatic light.
7. The microfluidic chip according to claim 6, wherein when the bottom plate is made of glass, the dispersion broadening range of the spectrum is 1-30 mm.
8. The microfluidic chip according to claim 6, wherein when the chip bottom plate is made of glass:
0.2mm≤s 3 ≤5mm;
0°≤α≤40°;0°≤β≤45°;-70°≤γ≤5.7°;11°≤δ≤75°;
0.1mm≤x 1 ≤3mm;0.1mm≤x 2 ≤3mm;
0.1mm≤x 3 ≤3mm;0.1mm≤x 4 ≤30mm;
wherein s is 3 The maximum distance between the second cambered surface and the intersection point of the first dispersion inclined plane and the optical axis of the first upper prism is set; alpha is an incident angle when the multi-color parallel light emitted from the second cambered surface passes through the first dispersion slope of the first upper prism or an included angle between the first dispersion slope of the first upper prism and a straight line perpendicular to the optical axis; beta is an included angle between the second dispersion inclined plane of the first upper prism and a straight line vertical to the optical axis; x is the number of 1 Is from the intersection point of the first dispersion slope and the optical axis to the secondDistance of intersection point of dispersion slope and optical axis; x is the number of 2 The distance from the intersection point of the second dispersion inclined plane and the optical axis to the intersection point of the third dispersion inclined plane and the optical axis is included; x is the number of 3 The distance from the intersection point of the third dispersion slope and the optical axis to the intersection point of the fourth dispersion slope and the optical axis.
9. The microfluidic chip according to any of claims 1 to 8, further comprising a transparent chip top cap, wherein the chip top cap is hermetically disposed on the chip bottom plate, and the chip top cap is provided with a sample inlet and a sample outlet, and the sample inlet and the sample outlet are correspondingly communicated with two ends of the sample channel.
10. A system for detecting spectral information, comprising: a spectroscopic detection device for detecting the spectrum and a microfluidic chip according to any one of claims 1 to 9.
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