This application claims priority to Taiwan Patent Application Serial Number 105112542, filed on Apr. 22, 2016, and Taiwan Patent Application Serial Number 105134719, filed on Oct. 27, 2016, which are herein incorporated by reference.
The invention relates to a biological sorting apparatus and a biological sorting method which uses the biological sorting apparatus for microparticles sorting.
Medical examination is a method of performing analyses on microparticles or biological molecules by utilizing various medical analysis instruments and assisting an evaluation of an organism's physical condition based on analyzing results. If only one type of microparticles is to be analyzed, a sorting process needs to be performed on different microparticles in a fluid. If the sorting result of the microparticles is not good, subsequent analyses to the microparticles would be severely affected, which results in analysis accuracy degradation. On the other hand, the conventional biological sorting instruments have high hardware cost, and hours or even tens of hours are required for such conventional biological sorting instruments to perform biological sorting. How to solve the abovementioned drawbacks has now become one of the major tasks in related industries.
An objective of the invention is to provide a biological sorting apparatus and a biological sorting method using the biological sorting apparatus having at least advantages of high sorting rate, low hardware cost and short time of a sorting process.
One aspect of the invention is directed to a biological sorting apparatus which includes a light-induced dielectrophoretic chip, a supporting platform, an injecting unit and a projection module. The light-induced dielectrophoretic chip is configured to generate an internal electric field to perform sorting on a fluid including first microparticles and second microparticles. The supporting platform is utilized to support the light-induced dielectrophoretic chip thereon and has an opening. The injecting unit is configured to inject the fluid into the light-induced dielectrophoretic chip. The projection module is disposed below the supporting platform and is configured to project a light pattern onto a projection area of the light-induced dielectrophoretic chip through the opening of the supporting platform, such that the light-induced dielectrophoretic chip produces a light-induced effect to change the internal electric field, thereby sorting out the first microparticles and the second microparticles.
In accordance with some embodiments of the invention, a wavelength of the patterned light source projected by the light source module is in a range from 280 nm to 1400 nm.
In accordance with some embodiments of the invention, the light-induced dielectrophoretic chip includes a first electrode layer, a second electrode layer, a semiconductor layer and a channel layer. The second electrode layer is disposed relative to the first electrode layer. The semiconductor layer is disposed on the first electrode layer. The channel layer is disposed between the second electrode layer and the semiconductor layer and defines an injecting region, a first accumulating region and a second accumulating region. The injecting region, the first accumulating region and the second accumulating region intersect in the projection area, the injecting region is configured to guide the fluid into the projection area, and the first accumulating region and the second accumulating region are configured to guide the sorted first microparticles and the sorted second microparticles, respectively.
In accordance with some embodiments of the invention, the second electrode layer includes an inlet interface, a first outlet interface and a second outlet interface. The inlet interface is adjacent to an input terminal of the injecting region, the inlet interface configured to let the fluid flow through the second electrode layer and into the injecting region. The first outlet interface is adjacent to an output terminal of the first accumulating region and is configured to let the first microparticles flow through the second electrode layer and out of the light-induced dielectrophoretic chip from the first accumulating region. The second outlet interface is adjacent to an output terminal of the second accumulating region and is configured to let the second microparticles flow through the second electrode layer and out of the light-induced dielectrophoretic chip from the second accumulating region.
In accordance with some embodiments of the invention, a thickness of the channel layer is substantially in a range from 30 microns to 100 microns.
In accordance with some embodiments of the invention, the thickness of the channel layer is substantially in a range from 40 microns to 60 microns.
In accordance with some embodiments of the invention, the projection module includes a light emitting element and a light modulator. The light emitting element configured to generate light. The light modulator is configured to convert the light into the light pattern.
In accordance with some embodiments of the invention, the light modulator is a digital micromirror device (DMD).
In accordance with some embodiments of the invention, the light modulator is a liquid crystal on silicon (LCoS) device.
In accordance with some embodiments of the invention, the light pattern is programmable.
In accordance with some embodiments of the invention, a size of the projection area is substantially in a range from 1 mm2 to 100 mm2.
In accordance with some embodiments of the invention, the size of the projection area is substantially 1.5×1.5 mm2.
In accordance with some embodiments of the invention, the biological sorting apparatus further includes a lens module disposed between the light-induced dielectrophoretic chip and the projection module for adjusting a size of the projection area.
In accordance with some embodiments of the invention, the lens module is disposed in the opening of the supporting platform.
In accordance with some embodiments of the invention, the biological sorting apparatus further includes an image detecting module configured to detect a sorting status of the fluid in the light-induced dielectrophoretic chip and to generate an analyzing result accordingly.
In accordance with some embodiments of the invention, the biological sorting apparatus further includes a power supply unit configured to supply power to the light-induced dielectrophoretic chip.
In accordance with some embodiments of the invention, a peak value of the voltage generated by the power supply unit is substantially in a range from 1 Volt to 50 Volts.
In accordance with some embodiments of the invention, a frequency of the voltage generated by the power supply unit is substantially in a range from 103 Hertz to 108 Hertz.
Another aspect of the invention is directed to a biological sorting method used for the biological sorting apparatus and including the following steps. A fluid having first microparticles and second microparticles is injected into the light-induced dielectrophoretic chip by the injecting unit in a speed of 2 mL/min to 200 mL/min. A voltage difference is provided to the light-induced dielectrophoretic chip, such that the light-induced dielectrophoretic chip generates an internal electric field accordingly. The projection module is arranged to project a light pattern onto the projection area of the light-induced dielectrophoretic chip through the opening of the supporting platform to change the internal electric field of the light-induced dielectrophoretic chip, such that the first microparticles and the second microparticles are sorted out by the internal electric field.
In accordance with some embodiments of the invention, the fluid injected into the light-induced dielectrophoretic chip has the first and second microparticles of micron-level.
The foregoing aspects and many of the accompanying advantages of this invention will become more readily appreciated as the same becomes better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings.
The detailed explanation of the present invention is described as following. The described preferred embodiments are presented for purposes of illustrations and description, and they are not intended to limit the scope of the present invention.
It will be understood that, although the terms “first” and “second” and may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another.
Please refer to
The structure of the light-induced dielectrophoretic chip 110 is shown in
The first electrode layer 220 is disposed on the lower substrate 210, including transparent conductive material, such as indium tin oxide (ITO), indium zinc oxide (IZO) or another similar conductive material.
The semiconductor layer 230 is disposed on the first electrode layer 220, and may include indirect bandgap material, such as silicon, germanium or another similar material. The semiconductor layer 230 may be formed of amorphous silicon, monocrystalline silicon, nanocrystalline silicon, polycrystalline silicon or a combination thereof.
The channel layer 240 is disposed on the semiconductor layer 230. Please also refer to
The second electrode layer 250 is disposed on the channel layer 240. In some embodiments, the second electrode layer 250 includes transparent conductive material, such as ITO, IZO or another similar conductive material. In this embodiment, the first electrode layer 220 and the second electrode layer 250 are electrically connected to an external power supply AC which provides a voltage difference to the first electrode layer 220 and the second electrode layer 250, such that an internal electric field is generated between the first electrode layer 220 and the second electrode layer 250.
The upper substrate 260 is disposed on the second electrode layer 250. The upper substrate 260 is an optically transparent substrate, such as a glass substrate or a plastic substrate, but is not limited thereto. In addition, an inlet interface IN and outlet interfaces OUT1 and OUT2 are disposed on the upper substrate 260. The inlet interface IN is configured to provide a path for the fluid to flow into the inlet interface 272, the outlet interface OUT1 is configured to provide a path for the first microparticles to flow to out of the light-induced dielectrophoretic chip 110 from the first outlet interface 274, and the outlet interface OUT2 is configured to provide a path for the second microparticles to flow to out of the light-induced dielectrophoretic chip 110 from the second outlet interface 276.
In some embodiments, the thicknesses of the lower substrate 210 and the upper substrate 260 are about 0.7 mm, the thicknesses of the first electrode layer 220 and the second electrode layer 250 are in a range from about 50 nm to about 500 nm, the thickness of the semiconductor layer 230 is in a range from about 1 micron to about 2 microns, and the thickness of the channel layer 240 is in a range from about 30 microns to about 100 microns. In certain embodiments, the thickness of the channel layer 240 is in a range from about 40 microns to about 60 microns. In addition, in some embodiments, the angle between the injecting region 273 and the first accumulating region 275 is about 169 degrees, the angle between the first accumulating region 275 and the second accumulating region 277 is about 22 degrees, the injecting region 273, the widths of the first accumulating region 275 and the second accumulating region 277 are in a range from about 0.8 mm to about 20 mm, and the calibers of the inlet interface 272, the first outlet interface 274 and the second outlet interface 276 are about 1.1 mm. In some embodiments, the size of the projection area 280 is in a range from about 1 mm2 to about 100 mm2. In certain embodiments, the size of the projection area 280 is about 1.5×1.5 mm2. The values (such as thicknesses, widths and/or angles) of each portion of the light-induced dielectrophoretic chip 110 may be adjusted according to practical requirements, but are not limited to the aforementioned values.
Referring back to
The projection module 130 is configured to generate a light pattern and to project the light pattern onto the light-induced dielectrophoretic chip 110 through the opening 120A of the supporting platform 120. The luminous exitance and the wavelength of the generated light pattern of the projection module 130 may be between 9×104 lux and 1.2×105 lux and between 280 nm and 1400 nm, respectively. In some embodiments, the wavelength of the generated light pattern is in a range from 300 nm to 380 nm, from 480 nm to 550 nm or from 700 nm to 900 nm.
The projection module 130 includes a light emitting element 132 and a light modulator 134. The light emitting element 132 is configured to generate light, which can be a lamp, an LED or a laser, but is not limited thereto. For example, the light emitting element 132 may be an LED which is used for emitting light including components in a wavelength range visible light. The light modulator 134 is configured to convert the light generated by the light emitting element 132 into a light pattern and to project the light pattern onto a projected area 280 shown in
The projection module 130 may communicatively connect with a computer device PC for receiving image data from the computer device PC and determining the light pattern to be outputted based on the received image data. Particularly, the projection module 130 may communicatively connect with a computer device PC by a wired communication method (such as VGA, HDMI, eDP and USB) or a wireless communication method (such as Wi-Fi and Bluetooth); after the communication between the projection module 130 and the computer device PC is established, the computer device PC transmits image data to the projection module 130, and then the light emitted by the light emitting element 132 is converted into a light pattern by the process of the light modulator 134 based on the image data. The projection module 130 may further include an element such as a lens and/or a reflector for adjusting the focus and/or the planar range of the light pattern.
The injecting unit 140 is connected to the inlet interface IN of the light-induced dielectrophoretic chip 110 for injecting a fluid including first microparticles and second microparticles into the light-induced dielectrophoretic chip 110. The injecting unit 140 may include a pump or another element which can control the injection speed of the fluid into the light-induced dielectrophoretic chip 110. In some embodiments, the injecting unit 140 injects the fluid into the light-induced dielectrophoretic chip 110 in a speed of 2 mL/min to 200 mL/min. The accumulating units 150A and 150B are respectively connected to the output interfaces OUT1 and OUT2 of the light-induced dielectrophoretic chip 110 for respectively accumulating the first and second microparticles flowing out from the light-induced dielectrophoretic chip 110.
The image detecting module 160 is disposed above the light-induced dielectrophoretic chip 110, and may be provided for a user to measure the sorting status in the light-induced dielectrophoretic chip 110. In some embodiments, the image detecting module 160 includes an image processing unit, which may perform an image analyzing process on a captured image of the sorting status and generate a analyzing result accordingly, and may real-time adjusting parameters of the biological sorting apparatus 100 (such as the planar projection image, the magnitude and/or the wavelength of the light pattern generated by the projection module 130, the distance between the light-induced dielectrophoretic chip 110 and the projection module 130, the size of the projection area 280 and the injecting speed of the injecting unit 140) according to the analyzing result. In other embodiments, the image detecting module 160 may be coupled to an entity which has image analyzing functionality, and the abovementioned image analyzing process may be performed in such entity.
Further, the biological sorting apparatus 100 may include a lens module 170 which is disposed between the light-induced dielectrophoretic chip 110 and the projection module 130 for adjusting the size of the projection area 280 of the light-induced dielectrophoretic chip 110. The magnification of the lens module 170 may be determined according to the architecture of the biological sorting apparatus 100, such as the distance between the light-induced dielectrophoretic chip 110 and the projection module 130, the structure of the channel layer 240 of the light-induced dielectrophoretic chip 110 and/or the luminous exitance of the projection module 130. The lens module 170 may be disposed in the opening 120A of the supporting platform 120, between the light-induced dielectrophoretic chip 110 and the opening 120A, or between the opening 120A and the projection module 130.
Please refer to
In the following, a sorting process to leukocyte cells and cancer cells (including colorectal cancer cells, lung cancer cells and breast cancer cells) is exemplified for description.
By using the biological sorting apparatus and the biological sorting method of the invention, the purity of the sorted microparticles can be up to higher than 85% (i.e. achieving high purity). In addition, in comparison with the conventional biological sorting instruments, the biological sorting apparatus of the invention has advantages of low hardware cost and sorting out microparticles with high purity in a shorter time. Therefore, the biological sorting apparatus of the invention is suitable for biological and medical applications, such as biochemical treatment and laboratory medicine.
It will be apparent to those skilled in the art that various modifications and variations can be made to the structure of the invention without departing from the scope or spirit of the invention. In view of the foregoing, it is intended that the invention cover modifications and variations of this invention provided they fall within the scope of the following claims.
Number | Date | Country | Kind |
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105112542 A | Apr 2016 | TW | national |
105134719 A | Oct 2016 | TW | national |
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9332236 | Fujioka | May 2016 | B2 |
20090170186 | Wu | Jul 2009 | A1 |
20120118740 | Garcia | May 2012 | A1 |
20160171686 | Du | Jun 2016 | A1 |
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102449163 | May 2012 | CN |
104048906 | Sep 2014 | CN |
200739075 | Oct 2007 | TW |
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Number | Date | Country | |
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20170304824 A1 | Oct 2017 | US |