Biological detection devices for analytes in biological targets and methods of manufacture and use

Abstract

Embodiments herein describe devices, methods for making the devices, and methods for detecting analytes in biological targets. The device includes a top component and a bottom component. The top component includes electrodes disposed on a top layer. The bottom component includes a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component. The polymer body includes a channel. The electrodes of the top component are located in the channel. The channel is configured to accommodate a biological target containing an analyte. Embodiments herein provide biological detection devices for analytes in biological targets and methods of manufacturing and using.

Description

Technical Field

[0001] The present application relates generally to electronic devices, and more particularly to detection devices for detecting biological targets. Background Art

[0002] Clinics and hospitals around the world use cell concentration to determine the health of patients because it can provide diagnostic information and / or indicate medical conditions. The accurate determination of cells in a sample is critical for a wide range of applications, such as microtissue culture studies performed by microbiologists and / or disease progression studies in medical laboratories. There are a variety of different methods to determine the number of cells in a sample, such as manual counting using a hemacytometer, using impedance systems (such as Coulter counter technology using benchtop and handheld devices), and / or using optical systems (such as optical flow cytometry). Summary of the invention

[0003] An embodiment of the present application provides a device for detecting an analyte in a biological target, the device comprising: a top component, including an electrode disposed on a top layer; and a bottom component, including a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component, wherein the polymer body comprises a channel, and the electrode is located within the channel, wherein the channel is configured to accommodate a biological target containing the analyte.

[0004] An embodiment of the present application also provides a method for manufacturing a device for detecting an analyte in a biological target, the method comprising: manufacturing a top component, the top component having an electrode disposed on an upper layer; molding a polymer body having a channel; and manufacturing a bottom component, the bottom component comprising a biochip disposed on a bottom layer; assembling the top component, the bottom component and the polymer body together, wherein the polymer body is between the top component and the bottom component, and wherein the electrode is located within the channel, and the channel is configured to accommodate a biological target including the analyte.

[0005] An embodiment of the present application also provides a method for detecting an analyte using a biological detection device, the method comprising: receiving a biological target having the analyte in a channel of a polymer body in the biological detection device; applying a voltage to a reference electrode of the biological detection device; and detecting the analyte in the biological target based on a current between the reference electrode and a biochip of the biological detection device, wherein the biological detection device comprises: a top component comprising an electrode disposed on a top layer; and a bottom component comprising a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component, wherein the polymer body comprises a channel, and the electrode is located in the channel. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Various aspects of the present invention are best understood from the following detailed description when read with the accompanying figures.

[0007] Figure 1 A top view of an exemplary biological detection device according to various embodiments of the present disclosure is shown.

[0008] Figure 2 The various embodiments of the present disclosure are shown along Figure 1 A side view of an exemplary biological detection device with section "A" marked in FIG.

[0009] Figure 3 The various embodiments of the present disclosure are shown along Figure 1 Another side view of an exemplary biological detection device of section “B” marked in FIG.

[0010] Figure 4 An exploded side view of another exemplary bio-detection device extracted from a top view according to various embodiments of the present disclosure is shown.

[0011] Figure 5 A side view of another exemplary bio-detection device having a biomarker 510 according to various embodiments of the present disclosure is shown.

[0012] Figure 6 A side view of another exemplary biological detection device according to various embodiments of the present disclosure is shown.

[0013] Figure 7 Exemplary biological target detection using a biological detection device according to various embodiments of the present disclosure is shown.

[0014] Fig. 8A A first stage in manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown.

[0015] Figure 8B A second stage in manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown.

[0016] Figure 8C A third stage in manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown.

[0017] Fig.8D A fourth stage in manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown.

[0018] Fig.9A A cross-sectional view of a reference electrode according to various embodiments of the present disclosure is shown.

[0019] Fig. 9BAnother cross-sectional view of a reference electrode according to various embodiments of the present disclosure is shown.

[0020] Fig. 9C Another cross-sectional view of a reference electrode according to various embodiments of the present disclosure is shown.

[0021] Fig.9D Another cross-sectional view of a reference electrode according to various embodiments of the present disclosure is shown.

[0022] Fig.10 Exploded view showing various patterns of reference electrodes of a top view of an exemplary bio-sensing device according to various embodiments of the present disclosure.

[0023] Fig.11 Exploded views showing various patterns of reference electrodes of a top view of an exemplary bio-sensing device according to various embodiments of the present disclosure.

[0024] Fig. 12A A side view of a silicon polymer body is shown according to various embodiments of the present disclosure.

[0025] Fig. 12B A top view of a silicon polymer body according to various embodiments of the present disclosure is shown.

[0026] Fig.13A A first stage of manufacturing a biological detection device according to various embodiments of the present disclosure is shown.

[0027] Fig. 13B A second stage of manufacturing a biological detection device according to various embodiments of the present disclosure is shown.

[0028] Fig. 13C A third stage of manufacturing a biological detection device according to various embodiments of the present disclosure is shown.

[0029] Fig.13D A fourth stage of manufacturing a biological detection device according to various embodiments of the present disclosure is shown.

[0030] Fig.14 An exemplary flow chart for manufacturing a biological detection device according to various embodiments of the present disclosure is shown.

[0031] Fig.15 An exemplary flow chart for detecting an analyte using a biological detection device according to various embodiments of the present disclosure is shown. DETAILED DESCRIPTION

[0032] The following disclosure provides many different embodiments or examples for realizing the different features of the provided subject matter. Specific examples of elements and arrangements are described below to simplify the present invention. Of course, these are only examples and are not intended to limit the present invention. Moreover, the present invention may repeat reference numbers and / or letters in each example. This repetition is only for simplicity and clarity, and does not itself represent the relationship between the various embodiments and / or configurations discussed.

[0033] In an embodiment, a biodetection device is described herein, which is used as a resistive sensor to detect and identify biological targets of various sizes, such as atoms, lipids, proteins, cells, bacteria, viruses, deoxyribonucleic acid (DNA), proteins and / or embryos. The detection of biological targets can be used, for example, for drug screening and / or instant diagnosis. The resistive sensor can measure electrical changes in a specific substance to be tested. With respect to the biodetection device, a sample of the biological target can be placed in an open space or channel in the biodetection device or passed through it. Once the biological target sample is in the biodetection device, a voltage is applied to the device and the electrical changes in the sample are measured. The height of the open space or channel can be adjusted to facilitate biological targets of various sizes. For example, the resolution width of the resistive sensor can depend on the displacement speed, and the amplitude can depend on the volume of the biological target, thereby allowing the size of the biological target to be extracted. Using the measured electrical changes and the adjusted height of the channel, the biological target sample can be detected and the characteristics can be identified. A method for manufacturing a biodetection device is also described herein.

[0034] Figure 1 A top view 100 of an exemplary biodetection device according to various embodiments of the present disclosure is shown. As can be seen from the top view 100, the biodetector includes a bio-MOSFET chip 110, a peripheral layer 120, and a silicon polymer body 130. The silicon polymer body 130 can be made of any silicon polymer. In one example, the silicon polymer body 130 is polydimethylsiloxane (PDMS). The silicon polymer body 130 includes a plurality of containers or channels 132. The biological target to be detected can be placed in the channel 132. The IA height of the channel 132 is variable and can be adjusted based on the type of biological target to be detected, such as in Figure 2 132. In some embodiments, the biological target to be detected is a liquid sample (e.g., blood or body fluid). The channel 132 includes a vent 134 that facilitates bubbling of the biological target once the biological target is placed in the channel 132. The peripheral layer 120 can surround the biological detection device. Depending on the location of the peripheral layer 120, the peripheral layer 120 can be any one of a printed circuit board (PCB), glass, acrylic, or poly (methyl methacrylate) (PMMA), such as in Figure 2 Described in more detail in .

[0035] Figure 2 The various embodiments of the present disclosure are shown along Figure 1 200 is a side view of an exemplary bio-detection device with a section “A” marked in FIG. 200 . As can be seen from the side view 200 , the bio-detection device includes a bio-MOSFET chip 110 , a silicon polymer body 130 , a reference electrode 232 , a bottom layer 222 , and a top layer 224 . The bottom layer 222 and the top layer 224 of the side view 200 together form Figure 1 The top view 100 of the bio MOSFET chip 110 is shown with a peripheral layer 120. According to some embodiments, the bio MOSFET chip 110 is located on a bottom layer 222, which is made on a PCB. The top layer 224 can be made of any of PCB, glass, or PMMA. The silicon polymer body 130 is located between the bio MOSFET chip 100 and the top layer 222. One or more channels 132 are formed in the silicon polymer body 130 to facilitate testing of biological targets or any other substances in the channels 132, such as in Figure 12A-12B The reference electrode is coupled to the top layer 224 and positioned within the channel 132, which is formed in Figure 8A-8D . The distance or height 234 between the surface of the bioMOSFET 110 and the reference electrode 232 can be adjusted according to the specific biological target being tested. These biological targets can include, for example, atoms, lipids, proteins, cells, bacteria, viruses, DNA, proteins and / or embryos, with logarithmic ranges of relative sizes from 0.1nm to 1mm (e.g., atoms ≈ 0.1nm, C60 ≈ 1nm, lipids ≈ 3nm, proteins ≈ 8nm, influenza virus ≈ 100nm, bacteria or mitochondria ≈ 1μm, red blood cells ≈ 7μm, animal and plant cells ≈ 10μ to 100μm, pollen or human eggs ≈ 300μm or frog eggs ≈ 1mm). The ratio between the size of the biological target and the height 234 between the reference electrode 232 and the surface of the bioMOSFET 110 is about 2:3. In some embodiments, the height 234 between the surface of the bioMOSFET 110 and the reference electrode 232 is adjusted by modifying the thickness of the reference electrode 232. The thickness of the reference electrode 232 can be in the range of 500μm to 2mm. The reference electrode may include materials such as gold (Au), platinum (Pt), silver (Ag), silver chloride (AgCl), or any combination thereof. In other embodiments, the height 234 between the surface of the bioMOSFET 110 and the reference electrode 232 is adjusted by modifying the thickness 236 of the silicon polymer body 130, which may be between 2.01 mm and 3 mm (e.g., 2.01 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm). In other embodiments, the height 234 between the surface of the bioMOSFET 110 and the reference electrode 232 is adjusted by modifying a combination of the thickness of both the reference electrode 232 and the silicon polymer body 130.

[0036] Figure 3 The various embodiments of the present disclosure are shown along Figure 1 Another side view 300 of an exemplary biological detection device is shown at section “B” labeled in FIG.

[0037] Figure 4 An exploded side view 400 of another exemplary biological detection device extracted from a top view 450 according to various embodiments of the present disclosure is shown. Figure 4 In the illustrated embodiment, the bio-MOSFET 110 may be an ion sensing field effect transistor (ISFET) comprised of a handle substrate 412, an interconnect 414, a polysilicon gate (PG) 416, a base 418, source / drain terminals 420, 422, an insulator layer 424, a metal interconnect layer 426, silicon 428, and a sensing membrane 430. The handle substrate 412 is coupled to the bottom layer 222. Each interconnect 414 couples each of the base 418, the source / drain terminals, and the PG 416 to the handle substrate 414. The metal interconnect layer 426 surrounds each of the interconnects 414 and the PG 416. The base 418 and the source / drain terminals 420, 422 are located within the silicon 428. An insulator layer 424 (e.g., a buried oxide layer) separates the sensing membrane 430 from the base. The sensing film 430 can be any high-k sensing film and include materials such as hafnium dioxide (HfO2), zirconium dioxide (ZrO2) and / or titanium dioxide (TiO2). The sensing film 430 forms a recessed well 440 between the source / drain terminals 420, 422. In some embodiments, the depth 444 of the recessed well 440 can be about 1 μm. The top view 450 shows that the size of the recessed wells such as the recessed well 452 can be varied to facilitate the detection of biological targets of different sizes. A solution 442 containing a buffer and a cell culture medium with a biological target fills the channel 132 and the recessed well 440. The sensing layer 430 contacts the source / drain terminals 420, 422 in the area of ​​the recessed well 440 to facilitate electrical connection between the bio-MOSFET 110 and the biological target being detected.

[0038] Figure 5 A side view 500 of another exemplary biodetection device having a biomarker 510 according to various embodiments of the present disclosure is shown. Figure 5As shown, one or more biomarkers 510 are bound to the surface of the bioMOSFET 110. More specifically, the one or more biomarkers 510 can be bound to the sensing membrane 430. The biomarkers 510 can be different cellular proteins that help identify a specific biological target within the solution 442. For example, a breast cancer cell biomarker is HER2. The protein of HER2 can be bound to the sensing membrane 420 within the well 440 and bind to any breast cancer cells contained within the solution 442. The solution 442 can be drained and the surface of the bioMOSFET 110 can be finally washed. In this example, any breast cancer cells bound to the biomarker 510 will remain on the surface of the sensing membrane 420 within the well 440, and those cells within the biological target can be identified as breast cancer cells. Although the description with respect to breast cancer cells and corresponding biomarkers is not limited to the embodiment of the present invention, the present invention is not limited to the embodiment of the present invention. Figure 5 The embodiments are shown, but it will be appreciated that any combination of biological targets and corresponding biomarkers may be used in conjunction with the biodetection devices described herein.

[0039] Figure 6 A side view 600 of another exemplary biosensing device according to various embodiments of the present disclosure is shown. In addition to the sensing membrane 630, the bioMOSFET 610 is similar in structure to Figure 4-Figure 5 The bio-MOSFET 110 described in FIG. Figure 6 As shown, the sensing film 630 is planar and has no wells.

[0040] Figure 7 An exemplary biological target detection using a biological detection device according to various embodiments of the present disclosure is shown. For ease of understanding, refer to the previous Figure 4-Figure 5 The process is described using the structure described in . However, it will be appreciated that the process is applicable to many other structures as well. In this example, the biological target 710 comprises a cardiac cell 712. In this example, the height or distance 734 between the reference electrode 232 and the surface of the biological MOSFET 110 (e.g., the surface of the sensing membrane 430) is approximately 2.05 mm. Figure 7 The biological target device shown can detect the presence of cardiac cells 734 (e.g., analyte) based on the electrical characteristics (e.g., current) between the reference electrode 232 and the biological MOSFET 110. The cardiac cells 712 include ions such as sodium ions (NA + ), potassium ion (K + ) and / or calcium ions (CA 2+ ) ions. Sodium ions (NA + ), potassium ion (K + ) and / or calcium ions (CA 2+) can enter and / or leave the biological target 710 and be detected by the sensing membrane 430. For example, when a person's heart beats, the heart cells 712 absorb extracellular calcium ions (CA 2+ ). When these extracellular ions are brought outside the body (e.g., within a biological target 710 sample), they are excreted from the cardiac cells 710, along with these extracellular calcium ions (CA 2+ ) is discharged from the heart cells, the extracellular calcium ion content decreases and is sensed by the sensing membrane 430. The current between the reference electrode 232 and the bioMOSFET 110 will be based on the extracellular calcium ions (CA 2+ ) and decrease.

[0041] Figure 8A-8D Various stages in fabricating a top electrode assembly having a top layer 224 and one or more reference electrodes 232 are shown in accordance with various embodiments of the present disclosure. Fig. 8A A first stage 800 of manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown. During the first stage 800, a metal layer 802 is deposited onto a substrate 804 using, for example, sputtering deposition. Sputtering deposition is a physical vapor deposition (PVD) method in which a thin film is deposited onto a substrate by applying an element in a gaseous state. In some embodiments, the metal layer 802 may include materials such as gold (Au), platinum (Pt), silver (Ag), silver chloride (AgCl), or any combination thereof. The substrate 804 (e.g., the top layer 224) may be composed of any of PCB, glass, acrylic, or PMMA.

[0042] Figure 8B 810 of manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown. During the second stage 810, a photoresist (PR) mask is applied to the metal layer 802 in preparation for etching. The PR mask can facilitate various types of patterning of the reference electrode 232, such as in Figure 10-11 Described in more detail in .

[0043] Figure 8C 820 of manufacturing a top electrode assembly according to various embodiments of the present disclosure is shown. During the third stage 820, the metal layer 802 is etched using a metal etch to pattern the metal layer 810 into the reference electrode 232. The various dimensions produced by this patterning during the third stage 820 are shown in FIG. Figure 9A-9D Described in more detail in .

[0044] Fig.8D A fourth stage 830 of fabricating a top electrode assembly according to various embodiments of the present disclosure is shown. During the fourth stage 830, once patterning of the metal layer 810 is completed, the PR layer 812 is removed and formation of the electrode 232 is completed.

[0045] Figure 9A-9D Various cross-sectional views of reference electrode 232 resulting from a manufacturing process are shown according to various embodiments of the present disclosure. Fig.9A A cross-sectional view 900 of a reference electrode 232 is shown according to various embodiments of the present disclosure. The length 902 of the reference electrode 232 may be in the range of 50 μm to 900 μm. Fig. 9B Another cross-sectional view 910 of a reference electrode 232 is shown according to various embodiments of the present disclosure. The width 912 of the reference electrode 232 may be in the range of 50 μm to 900 μm. Fig. 9B Another cross-sectional view 920 of reference electrode 232 is shown according to various embodiments of the present disclosure. The thickness 922 of reference electrode 232 may be between 100 μm and 2 mm.

[0046] The ratios between the thickness 922, width 912, and length 902 of the reference electrode 232 may be appropriately determined so as not to affect the adhesion of the reference electrode 232 on the surface of the bio-MOSFET 110. For example, in some embodiments, the ratio between the length 902 and the width 912 (e.g., L:W) may be about 1:18. In some embodiments, the ratio between the length 902 and the thickness 922 (e.g., L:T) may be about 1:5. Similarly, the ratio between the width 912 and the thickness 922 (e.g., W:T) may be about 1:5.

[0047] Fig.9D Another cross-sectional view 930 of a reference electrode 232 according to various embodiments of the present disclosure is shown. In this embodiment, the reference electrode 232 includes a bottom layer 932, a core material 934, and an outer layer 936. The deposition of these layers may be similar to that previously described in Fig. 8A The bottom layer 932 is composed of chromium (Cr). The core material 934 can be silver (Ag) or silver chloride (AgCl). The outer layer 936 can be graphene oxide (GO).

[0048] Fig.10 An exploded view of various patterns of reference electrode 232 is shown showing a top view 450 of an exemplary bio-sensing device in accordance with various embodiments of the present disclosure. Fig.10An exemplary biodetection device includes a single channel having a reference electrode 232 located within the channel. With this configuration, the single reference electrode 232 is patterned in a variety of ways. In one example, the channel 1002 may include a single electrode 1004 patterned so that a voltage is applied to a single site. In another example, the channel 1010 includes a single reference electrode patterned to have two sites: an internal site 1012 and an external site 1014. A voltage is applied to the internal site 1012 to concentrate the voltage. A voltage is applied to the external site 1014 to disperse the voltage across the reference electrode 1010. Sequentially applying voltage to both the internal site 1012 and the external site 1014 will result in a three-dimensional (3D) rotational motion of an analyte within the biological target being measured. In yet another example, the channel 1020 includes a single reference electrode patterned to have two side-by-side sites: a left site 1022 and a right site 1024. Sequentially applying voltage to the left site 1022 and the right site 1024 (eg, the left site 1022 to the right site 1024) results in a two-dimensional (2D) rotation of the analyte within the biological target being detected. The rotation of the analyte can improve the molecular pairing efficiency with the sensing membrane.

[0049] Fig.11 An exploded view of various patterns of reference electrode 232 is shown showing a top view 450 of an exemplary bio-sensing device in accordance with various embodiments of the present disclosure. Fig.11 The exemplary biosensing device of includes a single channel having a plurality of reference electrodes 232 located within the channel. With this configuration, the plurality of reference electrodes 232 are patterned in a variety of ways, such as Fig.10 In one example, channel 1102 can include multiple reference electrodes 1104. Each reference electrode is patterned so that a voltage is applied at a single site as described with respect to channel 1002. In another example, channel 1110 includes multiple reference electrodes 1114. Each reference electrode 1114 is patterned to have two sites, as described in detail with respect to channel 1004. In yet another example, channel 1120 includes multiple reference electrodes 1122. Each reference electrode is patterned to have two side-by-side sites, as described with respect to channel 1020.

[0050] Although the description of a single channel Figure 10-11 , but it will be appreciated that multiple channels with one or more electrodes may be used to detect analytes within a biological target. By using multiple channels, it may be desirable to separate the chambers according to the type of analyte.

[0051] Fig. 12AA side view 1200 of a silicon polymer body 130 according to various embodiments of the present disclosure is shown. In some embodiments, a PMMA mold is made using an engraving machine. Using the PMMA mold, the silicon polymer body 130 is formed by molding of PDMS. Fig. 12B A top view 1210 of a silicon polymer body 130 is shown according to various embodiments of the present disclosure.

[0052] Figures 13A-13D Various stages of manufacturing a biological detection device according to various embodiments of the present disclosure are shown. Fig.13A 1300 of manufacturing a biological detection device 1352 according to various embodiments of the present disclosure is shown. In the first stage 1300, two separate components are manufactured. Figure 8A-8D The top electrode assembly 1310 is manufactured as described in detail in FIG. As previously described, the top electrode assembly 1310 includes the top layer 224 and one or more reference electrodes 232. Figure 4-Figure 6 The bio-MOSFET chip 110 described in detail in is disposed on the bottom layer 222 to produce the bottom chip assembly 1320. As previously described in Figure 12A-12B The silicon polymer body 130 manufactured as described in the above is disposed on the bio-MOSFET chip 110 . Fig. 13B A second stage 1330 of manufacturing a biological detection device 1352 is shown in accordance with various embodiments of the present disclosure. During the second stage 1330, the top electrode assembly 1310 and the bottom electrode assembly 1320 are assembled together. Fig. 13C A third stage 1340 of manufacturing a biological detection device 1352 according to various embodiments of the present disclosure is shown. During the third stage 1340, an upper cover (eg, PMMA module) and a lower cover (eg, PMMA module) are manufactured using a laser engraver. Fig.13D A fourth stage 1350 of manufacturing a biodetection device 1352 is shown in accordance with various embodiments of the present disclosure. During the fourth stage 1350, the assembled top electrode assembly 1310 and bottom chip assembly 1320 are encapsulated within upper and lower covers 1342, 1344 to form the biodetector 1352.

[0053] Fig.14 An exemplary flow chart 1400 for manufacturing a biological detection device 1352 according to various embodiments of the present disclosure is shown. For ease of understanding, the process is described with reference to the structure previously described herein. However, it is understood that the process is also applicable to many other structures. In step 1402, as previously described in Figure 8A-8D The top assembly is manufactured as described in detail in . In step 1404, as previously described in Figure 12A-12B The silicone polymer body 132 is molded as described in detail in FIG. In step 1406, as described in Figures 13A-13DThe bottom assembly is manufactured as described in detail in .

[0054] Fig.15 An exemplary flow chart 1500 for detecting an analyte using a biological detection device 1352 according to various embodiments of the present disclosure is shown. For ease of understanding, the process is described with reference to the structures previously described herein. However, it is understood that the process is also applicable to many other structures. In step 1502, a biological target (e.g., biological target 710) having an analyte (e.g., cardiac cell 712) is received within a channel 132 of a polymer body 130 in the biological detection device 1352. During step 1502, a voltage is applied to a reference electrode 232 of the biological detection device 1352. For example, a voltage may be applied to the reference electrode 232 of the biological detection device 1352. For example, a voltage may be applied to the reference electrode 232 of the biological detection device 1352. Figure 10-11 The voltage is applied in various ways as discussed in detail in the above. The analyte (e.g., cardiac cell 712) in the biological target (e.g., biological target 710) is detected based on the current between the reference electrode 232 and the biochip 110 of the biological detection device 1352. The biological detection device can be Figure 4-Figure 7 and Fig.13D Any device described in detail in.

[0055] The use of a biodetector as described herein can provide many advantages in embodiments. For example, a biodetector integrated with an electrode and a bio-MOSFET chip has the advantages of high accuracy and high throughput, small size, and low cost, making it suitable for portable instant diagnosis. The design of the integrated detection device allows the distance between the RF electrode in the PDMS body container and the sensing surface of the bio-MOSFET chip to be modified or adjusted. This flexible design makes it suitable for detecting biological targets of various sizes in diagnostic analysis. For example, for diagnostic analysis of biological targets of various sizes, the distance between the electrode and the surface of the bio-MOSFET chip can be adjusted to be large enough to allow analytes of a specific size to pass through. The use of a biodetector as described herein can eliminate the need for cell staining and labeling, because cell identification can be performed by modifying the sensor surface with paired molecules.

[0056] In one embodiment, a device for detecting an analyte in a biological target includes a top component and a bottom component. The top component includes an electrode disposed on a top layer. The bottom component includes a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component. The polymer body includes a channel. The electrode is located in the channel. The channel is configured to accommodate a biological target containing an analyte.

[0057] In another embodiment, a method for making a device for detecting an analyte in a biological target includes: making a top component having an electrode disposed on an upper layer; molding a polymer body having a channel; and making a bottom component having a biochip disposed on a bottom layer. The top component, the bottom component, and the polymer body are assembled together, wherein the polymer body is between the top component and the bottom component. The electrode is located in the channel, and the channel is configured to accommodate a biological target containing an analyte.

[0058] In yet another embodiment, a method for detecting an analyte using a biodetection device includes receiving a biological target having an analyte in a channel of a polymer body in the biodetection device. A voltage is applied to a reference electrode of the biodetection device. The analyte is detected in the biological target based on a current between the reference electrode and a biochip of the biodetection device. The biodetection device includes: a top component having an electrode disposed on a top layer; a bottom component including a biochip disposed on a bottom layer; and a polymer body disposed between the biochip and the top component. The polymer body includes a channel, and the electrode is located in the channel.

[0059] Embodiments of the present application provide a device for detecting an analyte in a biological target, the device comprising: a top component, comprising an electrode disposed on a top layer; and a bottom component, comprising a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component, wherein the polymer body comprises a channel, and the electrode is located in the channel, wherein the channel is configured to accommodate a biological target containing the analyte. In some embodiments, the size of the analyte fits within the height of the channel, and the height is measured from the surface of the electrode in the channel and the top surface of the biochip. In some embodiments, the height of the channel is between 2.0 mm and 3.0 mm and can vary based on the thickness of the electrode or the thickness of the polymer body. In some embodiments, one or more biomarkers are bound to the surface of the biochip in the channel, the one or more biomarkers comprising proteins associated with the analyte. In some embodiments, the biochip comprises: a semiconductor substrate; a source and a drain electrode embedded in the semiconductor substrate; a channel layer disposed between the source electrode and the drain electrode; and a sensing dielectric layer disposed above the semiconductor substrate and on the channel layer. In some embodiments, the biochip is an ion-sensitive field effect transistor (IS-FET), and the sensing dielectric layer is an ion-sensitive dielectric layer. In some embodiments, the sensing dielectric layer includes at least one of hafnium dioxide (HfO2), zirconium dioxide (ZrO2), or titanium dioxide (TiO2). In some embodiments, the electrode includes at least one of platinum (Pt), gold (Au), silver (Ag), or silver chloride (AgCl). In some embodiments, the top layer includes at least one of a printed circuit board (PCB), glass, acrylic, or poly(methyl methacrylate) (PMMA), and the bottom layer includes a PCB. In some embodiments, the width of the electrode is between 50 μm and 900 μm, the length of the electrode is between 50 μm and 900 μm, and the thickness of the electrode is between 100 μm and 2 mm. In some embodiments, the ratio between the length and the width is 1:18, wherein the second ratio between the length and the thickness is 1:5, and wherein the third ratio between the width and the thickness is 1:5. In some embodiments, the electrode is patterned to have an inner site configured to receive a first voltage and an outer site configured to receive a second voltage, and wherein the electrode is capable of achieving a three-dimensional rotation of the analyte based on the sequential application of the first voltage and the second voltage. In some embodiments, the electrode is patterned to have a left site configured to receive a first voltage and a right site configured to receive a second voltage, and wherein the electrode is capable of achieving a two-dimensional rotation of the analyte based on the sequential application of the first voltage and the second voltage.

[0060] Embodiments of the present application also provide a method for manufacturing a device for detecting an analyte in a biological target, the method comprising: manufacturing a top component having an electrode disposed on an upper layer; molding a polymer body having a channel; and manufacturing a bottom component, the bottom component comprising a biochip disposed on a bottom layer; assembling the top component, the bottom component, and the polymer body together, wherein the polymer body is between the top component and the bottom component, and wherein the electrode is located in the channel, and the channel is configured to accommodate a biological target including the analyte. In some embodiments, the size of the analyte fits within the height of the channel, and the height is measured from the surface of the electrode in the channel and the top surface of the biochip. In some embodiments, it also includes: adjusting the height of the channel by manufacturing the electrode to have a first thickness or molding the polymer body to have a second thickness. In some embodiments, manufacturing the top component comprises: depositing a metal layer on the top layer; applying a photoresist layer on the metal layer; patterning the metal layer using metal etching; and removing the photoresist layer from the metal layer. In some embodiments, molding the polymer body comprises: manufacturing a poly(methyl methacrylate) (PMMA) mold having a plurality of channels; and molding the polymer body using the PMMA mold. In some embodiments, it further comprises: manufacturing an upper poly(methyl methacrylate) (PMMA) module and a lower PMMA module; and encapsulating the top assembly, the polymer body, and the bottom assembly between the upper PMMA module and the lower PMMA module.

[0061] An embodiment of the present application also provides a method for detecting an analyte using a biological detection device, the method comprising: receiving a biological target having the analyte in a channel of a polymer body in the biological detection device; applying a voltage to a reference electrode of the biological detection device; and detecting the analyte in the biological target based on a current between the reference electrode and a biochip of the biological detection device, wherein the biological detection device comprises: a top component comprising an electrode disposed on a top layer; and a bottom component comprising a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component, wherein the polymer body comprises a channel, and the electrode is located in the channel.

[0062] The components of several embodiments are discussed above so that those skilled in the art can better understand the various embodiments of the present invention. It should be understood by those skilled in the art that the present invention can be easily used as a basis to design or change other processing and structures to achieve the same purpose and / or achieve the same advantages as the embodiments introduced in the present invention. It should also be appreciated by those skilled in the art that these equivalent structures do not deviate from the spirit and scope of the present invention, and that various changes, substitutions and modifications may be made without departing from the spirit and scope of the present invention.

Claims

1. A device for detecting an analyte in a biological target, the device comprising: a top assembly including a plurality of electrodes disposed on the top layer; and A bottom component, comprising a biochip disposed on a bottom layer and a polymer body disposed between the biochip and the top component, wherein the polymer body comprises a channel, and a plurality of the electrodes are disposed in a single channel, Wherein, the channel is configured to accommodate a biological target containing the analyte.

2. The device according to claim 1, wherein The size of the analyte fits within the height of the channel, and the height is measured from the surface of the electrode within the channel and the top surface of the biochip.

3. The device according to claim 1, wherein The height of the channels is between 2.0 mm and 3.0 mm, and can vary based on the thickness of the electrode or the thickness of the polymer body.

4. The device according to claim 1, wherein One or more biomarkers are bound to the surface of the biochip within the channel, the one or more biomarkers including proteins associated with the analyte.

5. The device according to claim 1, wherein The biochip comprises: Semiconductor substrate; A source electrode and a drain electrode, embedded in the semiconductor substrate; a channel layer, disposed between the source electrode and the drain electrode; and A sensing dielectric layer is disposed above the semiconductor substrate and on the channel layer.

6. The device according to claim 5, wherein The biochip is an ion sensitive field effect transistor (IS-FET), and the sensing dielectric layer is an ion sensitive dielectric layer.

7. The device according to claim 5, wherein The sensing dielectric layer includes at least one of hafnium dioxide (HfO2), zirconium dioxide (ZrO2) or titanium dioxide (TiO2).

8. The device according to claim 1, wherein The electrode includes at least one of platinum (Pt), gold (Au), silver (Ag), or silver chloride (AgCl).

9. The device according to claim 1, wherein The top layer includes at least one of a printed circuit board, glass, acrylic, or polymethylmethacrylate, and the bottom layer includes a printed circuit board.

10. The device according to claim 1, wherein The width of the electrode is between 50 μm and 900 μm, the length of the electrode is between 50 μm and 900 μm, and the thickness of the electrode is between 100 μm and 2 mm.

11. The device according to claim 10, wherein A ratio between the length and the width of the electrode is 1:18, wherein a second ratio between the length and the thickness of the electrode is 1:

5.

12. The device according to claim 1, wherein The electrode is patterned to have an inner site configured to receive a first voltage and an outer site configured to receive a second voltage, and wherein the electrode is capable of achieving a three-dimensional rotation of the analyte based on sequential application of the first voltage and the second voltage.

13. The device according to claim 1, wherein The electrode is patterned to have a left site configured to receive a first voltage and a right site configured to receive a second voltage, and wherein the electrode is capable of achieving a two-dimensional rotation of the analyte based on sequential application of the first voltage and the second voltage.

14. A method of manufacturing a device for detecting an analyte in a biological target, the method comprising: manufacturing a top assembly having a plurality of electrodes disposed on an upper layer; molding a polymer body having a channel; as well as manufacturing a bottom assembly, the bottom assembly comprising a biochip disposed on a bottom layer; The top component, the bottom component, and the polymer body are assembled together, wherein the polymer body is between the top component and the bottom component, and wherein a plurality of the electrodes are disposed within a single channel, and wherein the channel is configured to accommodate a biological target including the analyte.

15. The method according to claim 14, wherein: The size of the analyte fits within the height of the channel, and the height is measured from the surface of the electrode within the channel and the top surface of the biochip.

16. The method according to claim 15, further comprising: The height of the channel is adjusted by manufacturing the electrode to have a first thickness or molding the polymer body to have a second thickness.

17. The method according to claim 14, wherein: Manufacturing the top assembly includes: depositing a metal layer on the upper layer; applying a photoresist layer on the metal layer; patterning the metal layer using a metal etch; and The photoresist layer is removed from the metal layer.

18. The method according to claim 14, wherein: Molding the polymer body comprises: manufacturing a polymethylmethacrylate mold having a plurality of channels; and The polymer body is molded using the polymethyl methacrylate mold.

19. The method according to claim 14, further comprising: manufacturing an upper polymethyl methacrylate module and a lower polymethyl methacrylate module; as well as The top assembly, the polymer body, and the bottom assembly are encapsulated between the upper polymethylmethacrylate module and the lower polymethylmethacrylate module.

20. A method for detecting an analyte using a biological detection device, the method comprising: receiving a biological target having the analyte in a channel of a polymer body in the bioassay device; applying a voltage to the electrodes of the biodetection device; as well as detecting the analyte in the biological target based on the current between the electrode and the biochip of the biological detection device, Wherein, the biological detection device comprises: a top assembly comprising a plurality of said electrodes disposed on a top layer; and The bottom component comprises a biochip arranged on a bottom layer and a polymer body arranged between the biochip and the top component, wherein the polymer body comprises a channel, and a plurality of the electrodes are arranged in a single channel.

Images