Detection device for specimens

The present disclosure relates to a detection device, and in particular to a detection device for specimens.

Various biochips, such as microfluidic chips, micro-array chips, or lab-on-a-chips, have been developed to detect human genome, and thus the research of sequencing human genome has been great improved. A person's blood can be analyzed to check whether the blood contains a biomarker for a specific disease. That is how so as a genetic diseases can be detected.

FIG. 1 is a schematic diagram of a conventional biochip detection device A 1 . The biochip detection device A 1 is used for detecting specimens A 2 carried on a biochip A 3 . The biochip A 3 includes a number of wells A 4 arranged in an array for receiving the specimens A 2 . The biochip detection device A 1 includes a laser source A 10 , a filter A 20 , a beam splitter A 30 , a lens A 40 , a filter A 50 , a lens A 60 and a detector A 70 .

The laser source A 10 emits an excitation beam L 1 toward the beam splitter A 30 . The filter A 20 is located between the laser source A 10 and the beam splitter A 30 and is used for filtering the excitation beam L 1 with a desired wavelength. For example, the wavelength of the excitation beam L 1 is in a range from about 300 nm to 500 nm. The beam splitter A 30 reflects the excitation beam L 1 to the specimen A 2 . The lens A 40 focuses the excitation beam L 1 on the specimen A 2 .

After the specimen A 2 is irradiated by the excitation beam L 1 , the specimen emits an induced beam L 2 to the filter A 50 by passing through the beam splitter A 30 . In general, the induced beam L 2 is a fluorescence beam. The filter A 50 is for blocking the excitation beam L 1 , since a portion of the excitation beam L 1 may pass through the beam splitter A 30 to the detector A 70 .

The lens A 60 is for focusing the induced beam L 2 on the detector A 70 . The detector A 70 is for analyzing the wavelength and the strength of the induced beam L 2 . However, since the excitation beam L 1 and the induced beam L 2 have the same optical path, the induced beam L 2 detected by the detector A 70 is distributed by the excitation beam L 1 . Therefore, thus the detection result of the specimen A 2 is influenced.

The conventional biochip detection device A 1 detects the specimen in a point-by-point manner, thus it will be very time-consuming whenever it scans a biochip A 3 with numerous specimens A 2 .

Moreover, as shown in FIG. 1 , the conventional biochip detection device A 1 includes a large amount of optical elements, and a transport device is also needed to move the biochip detection device A 1 for detecting the specimens A 2 in sequence. Therefore, the size and the weight of the biochip detection device A 1 is great, and the manufacturing cost of the biochip detection device A 1 is expensive. The biochip detection device A 1 is not portable or affordable for users.

Although biochip detection devices have been generally adequate for their intended purposes, they have not been entirely satisfactory in all respects. Consequently, it is desirable to provide a solution for improving biochip detection devices.

The present disclosure provides detection device for specimens with a small size and a light weight for portability. Moreover, the manufacturing cost of the detection device is decreased, and the time required for detection of the specimens is also decreased.

The present disclosure provides a detection device for specimens, including an image sensor, a light-guiding structure, a carrier, and a light source. The light-guiding structure is disposed on the image sensor, and includes a light-guiding layer and a number of guiding portions. The light-guiding layer is disposed on the image sensor. The guiding portions are disposed on the light-guiding layer and arranged in an array. The carrier is disposed on the light-guiding structure. The carrier has a number of wells arranged in an array located over the guiding portions. Each of the wells is configured to receive a specimen.

The light source is disposed on a side surface of the light-guiding layer and configured to emit an excitation beam into the light-guiding layer. The excitation beam is transmitted to the specimens via the guiding portions. The specimens emit induced beams when the specimens are irradiated by the excitation beam, and the induced beams are transmitted to the image sensor via the guiding portions and the light-guiding layer in sequence.

The present disclosure provides a detection device for specimens, including an image sensor, a light-guiding structure, a carrier, and a light source. The image sensor includes a number of microlenses arranged in an array. The light-guiding structure includes a light-guiding layer disposed on the microlenses, a top layer disposed on the light-guiding layer, and a transmitting layer disposed on the top layer. The carrier is disposed on the transmitting layer. The carrier has a number of wells arranged in an array. Each of the wells is configured to receive a specimen. The light source is disposed on a side surface of the transmitting layer and is configured to emit an excitation beam into the transmitting layer.

The microlenses are configured to reflect the excitation beam toward the wells via the guiding portions, and the top layer is configured to reflect the excitation beam in the light-guiding layer. The specimens emit induced beams when the specimens are irradiated by the excitation beam, and the induced beams are transmitted to the image sensor via the transmitting layer, the top layer, and the light-guiding layer in sequence.

In conclusion, since the detection device is integrated with the image sensor and the light-guiding structure, the size and the weight of the detection device are greatly decreased, and the manufacturing cost of the detection device is cheap. Moreover, the specimens on the carrier can be detected by the image sensor at the same time, and the thus the time required for detection of the specimens is decreased.

The invention can be more fully understood by reading the subsequent detailed description and examples with references made to the accompanying drawings, wherein:

FIG. 1 is a schematic diagram of a conventional biochip detection device;

FIG. 2 is a schematic view of a detection device in accordance with a first embodiment of the present disclosure;

FIG. 3 is a top view of the detection device in accordance with the first embodiment of the present disclosure;

FIG. 4 is a schematic view of a detection device in accordance with a second embodiment of the present disclosure;

FIG. 5 is a schematic view of a detection device in accordance with a third embodiment of the present disclosure;

FIG. 6 is a schematic view of a detection device in accordance with a fourth embodiment of the present disclosure;

FIG. 7 is a schematic view of a detection device in accordance with a fifth embodiment of the present disclosure; and

FIG. 8 is a schematic view of a detection device in accordance with a sixth embodiment of the present disclosure.

The following disclosure provides many different embodiments, or examples, for implementing different features of the present disclosure. Specific examples of components and arrangements are described below to simplify the present disclosure. For example, the formation of a first feature over or on a second feature in the description that follows may include embodiments in which the first and second features are formed in direct contact, and may also include embodiments in which additional features may be formed between the first and second features, such that the first and second features may not be in direct contact.

In addition, the present disclosure may repeat reference numerals and/or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed. Furthermore, the shape, size, and thickness in the drawings may not be drawn to scale or simplified for clarity of discussion; rather, these drawings are merely intended for illustration.

FIG. 2 is a schematic view of a detection device 100 in accordance with a first embodiment of the present disclosure. FIG. 3 is a top view of the detection device 100 in accordance with the first embodiment of the present disclosure. The detection device 100 includes an image sensor 1 , a light-guiding structure 2 , and light sources 4 . The light-guiding structure 2 is disposed on the image sensor 1 , and a carrier B 1 is disposed on the light-guiding structure 2 .

The carrier B 1 may be a biochip, such as a microfluidic chip, a micro-array chip, or a lab-on-a-chip. In this embodiment, the carrier B 1 is a micro-array chip. In some embodiments, the carrier B 1 is detachably disposed on the light-guiding structure 2 . In some embodiments, the carrier B 1 is fixed at and integrated with the light-guiding structure 2 .

The carrier B 1 is a plate structure, and includes a carrying body B 11 and a number of wells B 12 formed on the carrying body B 11 and arranged in an array. In some embodiments, the carrying body B 11 is made from transparent material, such as glass. Each of the wells B 12 is configured to receive a specimen B 2 . In some embodiments, the specimen B 2 includes blood, biological tissue, or DNA fragmentations.

The light sources 4 are disposed on side surfaces of the light-guiding structure 2 , and are configured to emit excitation beams L 1 . In some embodiments, the light sources 4 are laser sources, or LEDs (Light-Emitting Diodes). The wavelength of the excitation beam L 1 is in a range from about 200 nm to 500 nm. In other words, the excitation beam L 1 is a blue light beam or an ultraviolet light beam.

The light-guiding structure 2 is configured to transmit and guide the excitation beam L 1 to the specimen B 2 by passing through the carrying body B 11 . When the specimens B 2 are irradiated by the excitation beam L 1 , the specimens B 2 emit induced beams L 2 to the image sensor 1 . In some embodiments, the induced beams L 2 are fluorescence beams.

The image sensor 1 may be a CMOS (Complementary Metal-Oxide-Semiconductor) image sensor, a CCD (charge-coupled device) image sensor, or a SPAD (single-photon avalanche diode) image sensor. The image sensor 1 is manufactured by a semiconductor manufacturing process.

The image sensor 1 is a plate structure, and includes a sensing layer 10 , a cutting layer 20 , a number of filter units 30 , and a number of microlenses 40 . The sensing layer 10 extends along a reference plane P 1 . The sensing layer 10 is configured to sense the induced beams L 2 and generate detection signals according to the induced beams L 2 falling on the sensing layer 10 .

The sensing layer 10 may include all of the following elements, but the sensing layer 10 does not necessarily need to include all of the following elements since the objective of the sensing layer 10 is achieved. The sensing layer 10 includes a substrate 11 and a number of sensing units 12 . In some embodiments, the sensing layer 10 further includes other optional layers (not shown in figures).

The sensing units 12 are disposed in the substrate 11 . The sensing units 12 are arranged in an array at the reference plane P 1 . In some embodiments, the sensing units 12 are photodiodes. Each of the sensing units 12 is configured to sense the induced beam L 2 and generate a detection signal according to the induced beam L 2 falling thereon.

The cutting layer 20 is disposed between the sensing layer 10 and the microlenses 40 . In some embodiments, the cutting layer 20 is disposed between the sensing layer 10 and the filter units 30 . The cutting layer 20 is configured to block the excitation beam L 1 passing through to the sensing layer 10 .

The filter units 30 are disposed on the sensing layer 10 . The filter units 30 are arranged in an array on a plane parallel to the reference plane P 1 . Each of the filter units 30 20 is located over one of the sensing units 12 .

Each of the filter units 30 allows a predetermined range of wavelengths of light to pass. In some embodiments, the filter units 30 are color filter units 30 . For example, the filter units 30 include a number of red filter units 30 a and a number of filter units 30 b . The red filter units 30 a and the filter units 30 b are arranged alternately in an array.

The red filter units 30 a allow wavelengths of induced beam L 2 in a range from 620 nm to 750 nm (red light) to pass to the sensing unit 12 . The filter units 30 b allow wavelengths of light in a range from 590 nm to 620 nm to pass to the sensing unit 12 .

The microlenses 40 are disposed on the filter units 30 and arranged in an array at a plane parallel to the reference plane P 1 . Each of the microlenses 40 is located over one of the filter units 30 . The microlenses 40 are configured to focus the light to the sensing units 12 . The microlenses 40 are also configured to reflect the excitation beam L 1 toward the wells B 12 via the guiding portions 72 .

The light-guiding structure 2 is a plate structure parallel to the image sensor 1 and the carrier B 1 . In some embodiment, the light-guiding structure 2 is made by a semiconductor manufacturing process. The light-guiding structure 2 is integrated with the image sensor 1 .

The light-guiding structure 2 includes a bottom layer 50 , a light-guiding layer 60 , and a top layer 70 . The bottom layer 50 , the light-guiding layer 60 , and the top layer 70 are parallel to the reference plane P 1 and are transparent. The bottom layer 50 is disposed on the microlenses 40 of the image sensor 1 . In some embodiments, the bottom layer 50 is connected to the microlenses 40 .

The light-guiding layer 60 is disposed on the bottom layer 50 . As shown in FIGS. 2 and 3 , the light sources 4 are disposed on the side surfaces of the light-guiding layer 60 , and configured to emit excitation beams L 1 into the light-guiding layer 60 .

The top layer 70 is disposed on the bottom layer 50 . The top layer 70 includes a grid portion 71 and a number of guiding portions 72 . The grid portion 71 and the guiding portions 72 are disposed on the light-guiding layer 60 .

As shown in FIGS. 2 and 3 , the grid portion 71 is surrounding the guiding portions 72 , and the guiding portions 72 are arranged in an array. Each of the wells B 12 is located over one of the guiding portions 72 .

In some embodiments, the refractive index of the bottom layer 50 is in a range from about 1 to about 1.5. The refractive index of the light-guiding layer 60 is in a range from about 1.5 to about 3. The refractive index of the guiding portion 72 is in a range from about 1.5 to about 3. The refractive index of the grid portion 71 is in a range from about 1 to about 1.5.

In some embodiments, the refractive index of the light-guiding layer 60 is equal to the refractive index of the guiding portion 72 . The light-guiding layer 60 and the guiding portion 72 are made from the same material and formed as a single piece.

In some embodiments, the refractive indexes of the light-guiding layer 60 and the guiding portion 72 are greater than the refractive indexes of the bottom layer 50 .

In this embodiment, the light-guiding layer 60 is located between the bottom layer 50 and the top layer 70 . The grid portion 71 is configured to reflect the excitation beam L 1 in the light-guiding layer 60 by total internal reflection, and the bottom layer 50 is configured to reflect a portion of the excitation beam L 1 in the light-guiding layer 60 by total internal reflection. Therefore, the excitation beam L 1 can be transmitted along the light-guiding layer 60 .

In addition, the microlens includes a refractive index in a range from about 1.4 to about 2.3. The excitation beam L 1 directly transmitted to the microlens or reflected to the microlens by the grid portion 71 is reflected toward the wells B 12 via the guiding portions 72 by the microlenses 40 .

As shown in FIG. 2 , the light source 4 emits the excitation beam L 1 . A portion of the excitation beam L 1 is transmitted along light-guiding layer 60 by total internal reflection. Moreover, a portion of the excitation beam L 1 is transmitted to the microlenses 40 and is reflected by the microlenses 40 . Therefore, a portion of the excitation beam L 1 reflected by the microlenses 40 are transmitted to the specimens B 2 via the guiding portions 72 and the carrying body B 11 .

The specimen B 2 emits induced beam L 2 when the specimen B 2 is irradiated by the excitation beam L 1 . A portion of the induced beam L 2 is blocked by the grid portion 71 . A portion of the induced beam L 2 is transmitted to the image sensor 1 via the guiding portions 72 and the light-guiding layer 60 in sequence. When the induced beams L 2 fall on the image sensor 1 , the induced beams L 2 are transmitted to the sensing layer 10 via the microlenses 40 and the filter units 30 in sequence.

The induced beams L 2 are focused by the microlenses 40 . Each of the filter units 30 allows a predetermined range of wavelengths of the induced beams L 2 to pass. Each of the sensing units 12 generates a detection signal according to the induced beam L 2 falling thereon.

For example, if the induced beam L 2 is a red beam, the induced beam L 2 can pass through the red filter unit 30 a but is blocked by the filter unit 30 b . Therefore, the sensing unit 12 b corresponding to the red filter unit 30 a generates a detection signal, but the sensing unit 12 b corresponding to the filter unit 30 b does not generate a detection signal. Since the sensing units 12 a and 12 b correspond to the specimen B 2 a and the wells B 12 a , the color of the induced beam L 2 generated by the specimen B 2 a can be determined.

Since the detection device 100 is made by semiconductor manufacturing process, the size of the detection device 100 is small, and the weight of the detection device 100 is light. In some embodiments, the width or the length of the detection device 100 is in a range about 6.35 mm to about 12.7 mm, and the thickness of the detection device 100 is in a range about 3 um to about 4.5 um. Therefore, the detection device 100 is portable. Moreover, the manufacturing cost of the detection device 100 is cheaper than the conventional biochip detection device having a large amount of optical elements.

In addition, the image sensor 1 integrates with the light-guiding structure 2 , and the image sensor 1 senses the induced beams L 2 generated by the specimens B 2 at the same time. Therefore, the time required for detection of the specimens B 2 of the detection device 100 is decreased.

FIG. 4 is a schematic view of a detection device 100 in accordance with a second embodiment of the present disclosure. As shown in FIGS. 2 and 3 , the heights of the microlenses 40 are gradually increased from an edge area Z 1 of the detection device 100 to a central area Z 2 of the detection device 100 . By the structure of the light-guiding structure 2 , the excitation beam L 1 transmitted to the wells B 12 and the specimens B 2 are more uniform.

FIG. 5 is a schematic view of a detection device 100 in accordance with a third embodiment of the present disclosure. The light-guiding structure 2 further includes a transmitting layer 80 disposed on the top layer 70 . The carrier B 1 is disposed on the transmitting layer 80 . The light source 4 is disposed on a side surface of the transmitting layer 80 and configured to emit an excitation beam L 1 into the transmitting layer 80 .

A portion of the excitation beam L 1 in the transmitting layer 80 is directly transmitted to the specimens B 2 . The excitation beam L 1 transmitted to the light-guiding structure 2 is scattered at an interface E 1 of the light-guiding layer 60 and the top layer 70 or the top layer 70 when the excitation beam L 1 passes through the top layer 70 into the light-guiding layer 60 .

A portion of the excitation beam L 1 in the light-guiding layer 60 is reflected by the bottom layer 50 , and a portion of the excitation beam L 1 in the light-guiding layer 60 is transmitted toward the microlenses 40 . The excitation beam L 1 reflected by the bottom layer 50 may be transmitted to the interface E 1 and scattered at the interface E 1 or the top layer 70 . A portion of the excitation beam L 1 scattered at the interface E 1 or the top layer 70 may be transmitted toward the specimen B 2 or reflect by the interface E 1 .

The top layer 70 includes a number of the first grating portions 73 and a number of second grating portions 74 arranged alternately. In some embodiments, the first grating portions 73 and the second grating portions 74 are rod structures parallel to each other.

In some embodiments, the wells B 12 are not aligned with the first grating portions 73 (or the second grating portions 74 ). As shown in FIG. 5 , each of the first grating portions 73 (or the second grating portions 74 ) has an offset to a nearest well of the wells B 12 in a direction perpendicular to the top layer 70 , and the offsets are varied. In other words, some of the centers of the wells B 12 are respectively located over some of the centers of the first grating portions 73 (or second grating portions 74 ), and some of the centers of the wells B 12 are not located over some of the centers of the first grating portions 73 (or second grating portions 74 ).

In some embodiments, the wells B 12 are aligned with the first grating portions 73 (or the second grating portions 74 ). Each of the first grating portions 73 (or the second grating portions 74 ) has an offset to a nearest well of the wells B 12 in a direction perpendicular to the top layer 70 , and the offsets are the same. In other words, each of the wells B 12 is located over one of the first grating portions 73 (or the second grating portions 74 ). In some embodiments, each of the centers of the wells B 12 is respectively located over each of the centers of the first grating portions 73 (or second grating portions 74 ). In some embodiments, the wells B 12 are not located over the second grating portions 74 (or the first grating portions 73 ).

The refractive index of the first grating portions 73 is lower than the refractive index of the second grating portions 74 . In some embodiments, the refractive index of the light-guiding layer 60 is about 1 to 1.5 times the refractive indexes of the transmitting layer 80 and the first grating portions 73 .

In some embodiments, the refractive index of the transmitting layer 80 is equal to the refractive index of the first grating portions 73 . The transmitting layer 80 and the first grating portions 73 are made from the same material and are formed as a single piece.

In some embodiments, the refractive index of the light-guiding layer 60 is equal to the refractive index of the second grating portions 74 . The light-guiding layer 60 and the second grating portions 74 are made from the same material and formed as a single piece.

The thickness of the transmitting layer 80 is about 8 times to about 200 times the thickness of the light-guiding layer 60 , and the thickness of the light-guiding layer 60 is about 1 times to about 2 times the thickness of the top layer 70 .

In some embodiments, the width W 1 of the first grating portion 73 and the second grating portion 74 adjacent to the first grating portion 73 is in range from about one-quarter of the wavelength of the excitation beam L 1 to about half the wavelength of the excitation beam L 1 .

In some embodiments, the thickness of the transmitting layer 80 is in a range from about 8 um to about 200 um. The thickness of the light-guiding layer 60 is in a range from about 0.6 um to about 2 um. The thickness of the first grating portions 73 and the second grating portions 74 of the top layer 70 is in a range from about 0.1 um to about 0.5 um.

Accordingly, by the structure of the light-guiding structure 2 , most of the excitation beam L 1 can be transmitted to the specimens B 2 .

The microlenses 40 are configured to reflect the excitation beam L 1 toward the wells B 12 via the bottom layer 50 , the light-guiding layer 60 , the top layer 70 , and the transmitting layer 80 in sequence

The induced beams L 2 are transmitted to the image sensor 1 via the transmitting layer 80 , the top layer 70 , the light-guiding layer 60 , and the bottom layer 50 in sequence.

FIG. 6 is a schematic view of a detection device 100 in accordance with a fourth embodiment of the present disclosure. The heights H 1 relative to the transmitting layer 80 of the first grating portions 73 are gradually decreased from the edge area of the light-guiding structure 2 to the central area of the light-guiding structure 2 . Therefore, by the structure of the first grating portions 73 , the excitation beam L 1 transmitted to the wells B 12 and the specimens B 2 are more uniform.

FIG. 7 is a schematic view of a detection device 100 in accordance with a fifth embodiment of the present disclosure. The intervals W 3 between two adjacent first grating portions 73 are gradually increased from the edge area of the light-guiding structure 2 to the central area of the light-guiding structure 2 . Therefore, by the structure of the first grating portions 73 , the excitation beam L 1 transmitted to the wells B 12 and the specimens B 2 are more uniform.

FIG. 8 is a schematic view of a detection device 100 in accordance with a sixth embodiment of the present disclosure. The widths W 2 of the first grating portions 73 are gradually decreased from the edge area of the light-guiding structure 2 to the central area of the light-guiding structure 2 . Therefore, by the structure of the first grating portions 73 , the excitation beam L 1 transmitted to the wells B 12 and the specimens B 2 are more uniform.

In conclusion, since the detection device is integrated with the image sensor and the light-guiding structure, the size and the weight of the detection device are greatly decreased, and the manufacturing cost of the detection device is cheap. Moreover, the specimens on the carrier can be detected by the image sensor at the same time, and the thus the time required for detection of the specimens is decreased.

While the invention has been described by way of example and in terms of preferred embodiment, it is to be understood that the invention is not limited thereto. On the contrary, it is intended to cover various modifications and similar arrangements (as would be apparent to those skilled in the art). Therefore, the scope of the appended claims should be accorded the broadest interpretation so as to encompass all such modifications and similar arrangements.