Sample testing apparatus, manufacturing method thereof, and sample testing method
11623216 · 2023-04-11
Assignee
- Beijing Boe Optoelectronics Technology Co., Ltd. (Beijing, CN)
- Boe Technology Group Co., Ltd. (Beijing, CN)
Inventors
Cpc classification
C12M1/34
CHEMISTRY; METALLURGY
B01L2300/0636
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0829
PERFORMING OPERATIONS; TRANSPORTING
B01L3/5085
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502707
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
H01L23/538
ELECTRICITY
International classification
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
C12M1/34
CHEMISTRY; METALLURGY
G01N33/52
PHYSICS
Abstract
A sample testing apparatus for characterizing at least one target molecule in a testing sample includes a substrate and at least one detection device over the substrate. Each detection device includes a plurality of electrodes, a plurality of data lines, and a probe. Each electrode is configured, upon reaction of the probe with one of the at least one target molecule, to sense an electrical signal, and then to transmit the electrical signal via the one data line. Each data line includes a first film layer and at least one other film layer disposed over the first film layer. The first film layer can be at a substantially same layer, and have a first composition substantially same, as the electrodes. One or more of the at least one other film layer can have a composition having a relatively lower electric resistance than the first composition.
Claims
1. A sample testing apparatus for characterizing at least one target molecule in a testing sample, comprising: a substrate; and at least one detection device over the substrate, each comprising: an accommodating space formed within a packaging portion, the packaging portion extending perpendicular from the substrate; a plurality of data lines, each of the plurality of data lines comprising a first film layer abutting the substrate and a second film layer on an opposite side of the first film layer from the substrate; a plurality of electrodes abutting the substrate within the accommodating space, the plurality of electrodes being formed from a common layer as the first film layer such that electrical resistance of the data lines are reduced and the plurality of probes have improved compatibilities with the testing sample; and a probe extending away from the substrate within the accommodating space, the probe configured to react with one of the at least one target molecule; wherein: each of the plurality of electrodes is electrically coupled to one of the plurality of data lines; each of the plurality of electrodes is configured, upon reaction of the probe with the one of the at least one target molecule, to sense an electrical signal, and then to transmit the electrical signal via the one of the plurality of data lines; the first film layer extends along the substrate from outside the accommodating space to inside the accommodating space; the first film layer has a first composition; the second film layer has a second composition; the second composition has an electrical resistance lower than an electrical resistance of the first composition; and the at least one detection device over the substrate each further comprises: a conductive layer disposed over the plurality of electrodes; and a probe base layer disposed over the conductive layer and configured to provide a surface for attaching or growing the probe to specifically react with the one of the at least one target molecule.
2. The sample testing apparatus of claim 1, wherein in each of the at least one detection device, the plurality of electrodes are grouped into at least one subset of electrodes, wherein: each of the at least one subset of electrodes are electrically coupled to a same data line.
3. The sample testing apparatus of claim 2, wherein in each of the at least one detection device, the plurality of data lines comprise a first data line and a second data line; and the plurality of electrodes are grouped into two subsets of electrodes, electrically coupled to the first data line and the second data line respectively.
4. The sample testing apparatus of claim 3, wherein in each of the at least one detection device, the plurality of electrodes are arranged in a matrix having a plurality of rows, wherein: electrodes in each of the plurality of rows are connected to one another in series; one of the two subsets of electrodes comprises electrodes in odd-number rows; and another of the two subsets of electrodes comprises electrodes in even-number rows.
5. The sample testing apparatus of claim 1, wherein the packaging portion encircles the plurality of electrodes and the testing sample.
6. The sample testing apparatus of claim 5, wherein each of the at least one detection device further comprises, within the accommodation space: a conductive layer over a side of the plurality of electrodes distal to the substrate; and a probe base layer over a side of the conductive layer distal to the substrate, configured to provide a surface for attaching or growing molecules of the probe thereon.
7. The sample testing apparatus of claim 6, wherein each of the conductive layer and the probe base layer is formed having a common pattern with the plurality of electrodes.
8. A method for manufacturing the sample testing apparatus of claim 1, comprising: providing the substrate; and forming the at least one detection device over the substrate.
9. The method according to claim 8, wherein the forming at least one detection device over the substrate comprises: forming the plurality of electrodes and the first film layer of each of the plurality of data lines over the substrate; and forming the at second film layer of the each of the plurality of data lines over a side of the first film layer distal to the substrate.
10. The method according to claim 9, wherein the forming the plurality of electrodes and the first film layer of each of the plurality of data lines over the substrate is performed by using a single mask.
11. The method according to claim 9, wherein the forming at least one detection device over the substrate further comprises: forming a conductive layer over a side of the plurality of electrodes distal to the substrate; forming a probe base layer over a side of the conductive layer distal to the substrate; and forming the probe on a surface of the probe base layer distal to the substrate.
12. The method according to claim 11, wherein the package portion encircles the plurality of electrodes to thereby form an accommodation space for the testing sample.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION
(13) In the following, with reference to the drawings of various embodiments disclosed herein, the technical solutions of the embodiments of the disclosure will be described in a clear and fully understandable way.
(14) It is obvious that the described embodiments are merely a portion but not all of the embodiments of the disclosure. Based on the described embodiments of the disclosure, those ordinarily skilled in the art can obtain other embodiment(s), which come(s) within the scope sought for protection by the disclosure.
(15) In existing sample testing chips such as a genetic testing chip, or a DNA testing chip, each of the data lines used to collect electric signals typically comprises a one-layer metal, and because of such a structure, the data lines usually have a high electric resistance, which commonly leads to a high testing noise during normal sample testing analysis. The high testing noise has significantly limited the wide application of the technology utilizing the sample testing chips. Therefore, how to reduce the testing noise of a gene detection chip has become a technical issue that needs to be urgently solved in this field.
(16) In light of this above technical issue associated with existing sample testing apparatus, the present disclosure provides a sample testing apparatus, its manufacturing method, and a sample testing method using the sample testing apparatus.
(17) In a first aspect, the present disclosure provides a sample testing apparatus.
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(19) In the sample testing apparatus, each of the plurality of detection devices m is substantially a sample detection unit that includes a plurality of electrodes 01, and a plurality of data lines 02 electrically coupled to each of the plurality of electrodes 01, as illustrated in
(20) The plurality of electrodes 01 are configured to have a composition of a conductive material having a relatively good compatibility with the sample to be tested. Herein the good compatibility with the sample to be tested is defined as a characteristics of a material, such as the conductive material used for the plurality of electrodes 01, that the material itself does not interfere with the reactions of molecules in the sample to be tested with the probes in each detection device (e.g. not prone for any physical or chemical reactions that may interfere) or with the detection of electrical signals obtained from each of the plurality of electrodes 01 and transmitted via the plurality of data lines 02.
(21) Examples of some commonly used conductive material can be a noble metal, such as gold (Au), silver (Ag) and platinum (Pt), etc. It should be noted that the conductive material can also be another metal, an alloy, or even a non-metal conductive material as long as it meets the requirement that it has a relatively good compatibility with the sample to be tested.
(22) Each of the plurality of detection devices comprises a probe that is configured to specifically characterize a target molecule in a testing sample. Herein the characterization of the target molecule can include a qualification, and/or quantification of the target molecule in the testing sample.
(23) The probe and the target molecule substantially form a corresponding pair of reacting partners, which can be a pair of binding partners including a DNA-DNA pair, a DNA-RNA pair, a RNA-DNA pair, an antibody-antigen pair, an antigen-antibody pair, a biotin-streptavidin pair, etc., but can also be a pair of reactants in a chemical reaction.
(24) According to some embodiments, the probes 05 in a detection device of the sample testing apparatus are a plurality of oligo nucleotides with a first sequence, which can hybridize specifically with target nucleic acid molecules (e.g. DNA or RNA) having a second sequence complimentary to the first sequence of the probes. These above embodiments of the sample testing apparatus can be particularly useful for a DNA sequencing array.
(25) According to some other embodiments, the probes in a detection device of the sample testing apparatus are a plurality of antibodies, and the target molecules in the testing sample can have an epitope that can be specifically bound by the antibodies.
(26) In the specific embodiments of the sample testing apparatus as illustrated in
(27) The plurality of electrodes 01 in each detection device m are further grouped into a plurality of subsets. The electrodes 01 in each subset are electrically connected to one another in series, and are all configured to be electrically coupled to one same data line 02 (i.e. 02-1 or 02-2).
(28) In the specific embodiment of the detection device as shown in
(29) It is noted that the above configuration of electrodes and data lines for the detection devices serves as an illustrating example only, and shall not be interpreted as a limitation to the scope of the disclosure. Other embodiments for the arrangement of electrodes 01 and data lines 02 are also possible. For example, each electrode 01 can be of a shape other than a circle, which can be a squire, a triangle, a rectangle, or any other shape depending on practical needs and specific design. The plurality of electrodes 01 can be arranged in an array of strip-shaped electrodes (i.e. array of electrode strips, not shown in the drawings). The specific grouping of electrodes 01 and the electrical coupling between each electrode 01 and each data line 02 can take any configuration.
(30) In the sample testing apparatus disclosed herein, each of the plurality of data lines is configured to have a relatively low electrical resistance, which can reduce the testing noise during normal sample testing analysis compared with conventional design where each data line has only one-layer of metal. As such, each data line can be configured to have a special composition, and/or a special structure, to thereby realize that it has a relatively low electrical resistance.
(31) According to some embodiments, each data line substantially comprises a multilayer structure having a plurality of film layers, thereby causing each data line to have a reduced electrical resistance compared with otherwise. Specifically, the multilayer structure for each data line comprises a first film layer over the substrate, and at least one other film layer over the first film layer.
(32) Optionally, the first film layer of each data line can be configured to be at a substantially same layer as the plurality of electrodes. Furthermore, the first film layer of each data line can be additionally configured to have a substantially same composition as the plurality of electrodes (i.e. the aforementioned conductive material). In other words, according to some embodiments, the first film layer can be configured to be at a substantially same or different layer as, and have a substantially same or different composition as, the plurality of electrodes.
(33) It is noted that there is no limitation to the relative position and composition of the first film layer, or to the relatively arrangement of, and/or to the composition of, each of the at least one other film layer, as long the multilayer structure composed of the first film layer and the at least one other film layer has a relatively low electrical resistance.
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(35) Further as illustrated in
(36) By the above configuration (i.e., the first film layer 021 of each data line 02 is at a substantially same layer as the plurality of electrodes 01, and has a composition that is substantially same as the conductive material used for the plurality of electrodes 01), the first layer 021 of each data line 02 and the plurality of electrodes in each detection device can be manufactured by a substantially same process, for example, a patterning process. In addition, the conductive material has a relatively good compatibility with the testing sample, allowing the sample testing to be carried out without the unwanted interference.
(37) In the embodiment as shown in
(38) According to some embodiments, the second composition can be further configured to have a relatively lower electric resistance than the first composition used for the first film layer 021. As such, the electric resistance of the data line 02 can be further reduced, in turn leading to a further reduced testing noise of the sample testing apparatus.
(39) It is noted that in each data line 02, the at least one other film layer over the first film layer 021 can further comprise film layers in addition to the second film layer 022 (not shown in the drawings), such as a third film layer, a fourth film layer, etc. Each of these other film layers can have a composition that is same as, or different from, the composition for the first film layer 021 or for the second film layer 022, as long as the multilayer data line as a whole has a reduced electric resistance. Preferably, each of these other film layers can have a composition having a relatively lower electric resistance than the first composition used for the first film layer 021.
(40) To manufacture the plurality of data lines 02 having the above configuration (i.e. each data line 02 has a first film layer 021 and at least one other film layer, such as a second film layer 022), a manufacturing process of several rounds of superposition or of several rounds of mask preparation can be applied.
(41) As such, in each of the plurality of data lines 02 being manufactured thereby, a first portion thereof that is at a substantially same layer as the plurality of electrodes 01 can be configured to have a substantially same composition as the plurality of electrodes 01, and a second portion thereof that is over the first portion can be configured to have at least one metal film layer over the first portion, each configured to have a composition of a relatively lower electric resistance. Such a configuration allows the plurality of electrodes 01 to be relatively compatible with the genetic materials to be tested, and also reduces the electric resistance of each of the plurality of data lines 02.
(42) It is noted that in addition to the above embodiment as illustrated in
(43) Further as illustrated in
(44) In order to realize a detection of target molecules in a testing sample, each detection device of the sample testing apparatus further comprises a packaging portion 06, which is configured to package the plurality of electrodes 01 to thereby form an accommodation space for accommodating the sample to be tested (i.e. testing sample). The accommodating space is substantially a reaction and detection space for each detection device of the sample testing apparatus, where the testing sample can be loaded, be allowed to react with the probes 05, and be qualitatively and/or quantitatively analyzed for the specific reaction via the electrical signals from the plurality of electrodes 01 and transmitted through the plurality of data lines 02.
(45) In this embodiment of the detection device of the sample testing apparatus described herein and illustrated in
(46) It is noted that in addition to the embodiment of the detection device of the sample testing apparatus described above and illustrated in
(47) For example, in yet another embodiment of the detection device of the sample testing apparatus as illustrated in
(48) Yet there is at least one feature of the embodiment shown in
(49) It is noted that the sample testing apparatus can include more than one detection device. Each of the more than one detection device can be provided with one different probe that is configured to specifically test one different target molecule in the testing sample in the sample testing analysis utilizing the sample testing apparatus. As such, the sample testing apparatus can realize a simultaneous detection of more than one target molecules in the testing sample, resulting in an elevated throughput and an increased efficiency. The more than one detection device can be arranged in a matrix over the substrate, but can have other arrangements.
(50) In the embodiments of the sample testing apparatus as described above, each of the plurality of data line 02 is configured to have a multilayer structure which comprises a plurality of film layers. The first film layer 021 in each data line can be configured to have a substantially same composition, and be arranged at a substantially same layer, as the plurality of electrodes 01. As such, in addition that the compatibility of the plurality of electrodes 01 with the genetic materials to be tested can be guaranteed, the electric resistance of the data line can be reduced, which in turn can reduce the noise (i.e. the testing noise as mentioned above) during a sample testing process utilizing the sample testing apparatus.
(51) In a second aspect, the present disclosure further provides a method for manufacturing the sample testing apparatus as described above.
(52) Specifically, the manufacturing method comprises:
(53) S100: Forming a plurality of detection devices over a substrate.
(54) Herein each of the plurality of detection devices can be referenced to the various embodiments of the detection device as described above. Specifically, each detection device can comprise a plurality of electrodes and a plurality of data lines electrically coupled to each electrode.
(55) The plurality of electrodes can be grouped into a plurality of subsets, and each electrode in each subset is configured to be electrically coupled to a same data line. Each data line has a multilayer structure. A first film layer in each data line is configured to be at a substantially same layer, and have a substantially same composition, as the plurality of electrodes. A conductive material having a relatively good compatibility with the testing sample can be used as the composition for the plurality of electrodes and for the first film layer of each data line. At least one another film layers other than the first film layer is configured to have a composition having a relatively lower electric resistance than the conductive material to thereby result in a reduced electric resistance for each data line.
(56) In the sample testing apparatus manufactured by the method as described above, the plurality of electrodes are configured to be relatively compatible with the genetic materials to be tested, and the electric resistance of each of the plurality of data lines can also be reduced, leading to a reduced noise during testing.
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(58) As illustrated in
(59) S101: Forming the plurality of electrodes 01 and the first film layer 021 of each of the plurality of data lines over the substrate; and
(60) S102: Form the at least one other film layer over the first film layer to thereby form the multilayer structure for each of the plurality of data lines.
(61) Specifically, the step S101 can be performed by several alternative patterning processes, which all result in the formation of the plurality of electrodes 01 and the first film layer 021 of each data line over the substrate, as illustrated in
(62) According to some embodiments, sub-step S101 may include a one-time patterning process, which can involve the use of a single mask having a specific pattern to directly form the plurality of electrodes 01 and the first film layer 021. As such, as illustrated in
(63) S1010: Using a single mask to directly form the plurality of electrodes 01 and the first film layer 021 of each of the plurality of data lines over the substrate.
(64) According to some other embodiments, sub-step S101 may include an etching process after the formation of a conductive material layer over the substrate. As such, as illustrated in
(65) S1011: forming a conductive material layer over the substrate; and
(66) S1012: performing an etching process over the conductive material layer to form the pattern of the plurality of electrodes 01 and the first film layer 021.
(67) It is noted that besides the above two different patterning processes, it is possible the S101 can include other alternative fabrication processes.
(68) Specifically, the step S102 can be performed by means of at least one patterning process over the substrate having the plurality of electrodes and the first film layer. The data line 02 having a multilayer structure after the step S102 according to some embodiments is illustrated in
(69) According to some embodiments of the manufacturing method, the multilayer structure for each data line comprises at least one other film layer over the first film layer and contains no insulating layers. As such, as illustrated in
(70) S1020: sequentially forming the at least one other film layer directly on the first film layer.
(71) Herein the formation of each of the at least one other film layer in S1020 can be performed by a patterning process, such as a one-time patterning process using a single mask or a patterning process involving an etching process.
(72) It is noted that in the sample testing apparatus manufactured by this above embodiment of the manufacturing method, there are at least two film layers that are directly stacked over one another (without the insulation layer having vias therebetween).
(73) According to some other embodiments of the manufacturing method, the multilayer structure for each data line comprises an insulating layer, which is arranged between the first film layer and the at least one other film layer, and/or between two neighboring other film layers. As such, as illustrated in
(74) S1021: Forming an insulating layer 07 over the substrate having the plurality of electrodes 01 and the first film layer 021, and treating the insulating layer 07 such that each of the plurality of electrodes 01 is exposed and at least one via k is formed in the insulating layer 07.
(75) Specifically, the exposure of the plurality of electrodes 01 and the formation of the at least one via k in the insulating layer 07 can be performed by using a single mask (i.e. a one-time mask etching process). The vias k are illustrated in
(76) S1022: Forming a second film layer 022 over the first film layer 021 such that the second film layer 022 is electrically connected with the first film layer 021 through the at least one via k.
(77) Specifically, the second film layer 022 can be formed by firstly forming a composition layer over the insulating layer having the at least one via k, and secondly performing a patterning over the composition layer to thereby form the second film layer 022. The patterning can be a one-time mask etching process, and the second film layer 022 formed is illustrated in
(78) Optionally, the multilayer structure of each data line comprises two or more other film layers (i.e. second film layer, third film layer, etc., over the first film layer), which are insulated from one another by one insulating layer in between. As such, the sub-step S102 can further include:
(79) S1023: repeating S1021 and S1022 for N times (N=0, 1, 2, . . . ) until all other film layers in the each of the plurality of data line are formed.
(80) Specifically, each of the other film layers (i.e. a third film layer, a fourth film layer, etc.) in the data line can be formed by a patterning process as mentioned above (i.e. a one-time mask etching process for the second film layer 022), until the multilayer structure of the data line is formed.
(81) It also noted that similar to the above mentioned sub-step S101 to form the plurality of electrodes 01 and the first film layer 021, at least one of the sub-steps (e.g. S201, S202, etc.) can also involve the fabrication process involving the formation of a material layer and a subsequent patterning (e.g. etching) over the material layer to thereby form the pattern of one specific layer (e.g. the insulating layer 07, the second film layer 022, etc.)
(82) In the above mentioned method for manufacturing a sample testing apparatus, the step S100 of forming a plurality of detection devices over a substrate can further include sub-steps that substantially form each individual detection device of the sample testing apparatus.
(83) According to some embodiment of the manufacturing method which substantially results in the detection device having a structure as illustrated in
(84) As shown in
(85) S100a: Forming a pattern of the plurality of electrodes 01 and the data lines 02 on the substrate S (the intermediate product after S100a is shown in
(86) S100b: Forming a conductive layer 03 on the plurality of electrodes 01, and not on the data lines 02 (the intermediate product after S100b is shown in
(87) S100c: Forming a probe base layer 04 over the conductive layer 03 (the intermediate product after S100c is shown in
(88) S100d: Forming probes 05 on a surface of the probe base layer 04 that is distal to the substrate (the intermediate product after S100d is shown in
(89) S100e: Forming packaging portion 06 surrounding the plurality of electrodes 01, the conductive layer 03, the probe base layer 04, and the probes 05 to thereby form an accommodating space for accommodating the sample to be tested (the intermediate product after S100e is shown in
(90) According to some other embodiments of the manufacturing method which substantially results in the detection device having a structure as illustrated in
(91) S100a′: Forming a pattern of the plurality of electrodes 01 and the data lines 02 on the substrate S;
(92) S100b′: Forming a pattern of conductive layer 03 over the plurality of electrodes 01, such that the pattern of conductive layer 03 is substantially same as the pattern of the plurality of electrodes 01;
(93) S100c′: Forming a pattern of probe base layer 04 over the conductive layer 03, such that the pattern of probe base layer 04 is substantially same as the pattern of the conductive layer 03;
(94) S100d′: Forming probes 05 on a surface of the probe base layer 04 that is distal to the substrate; and
(95) S100e′: Forming packaging portion 06 surrounding the plurality of electrodes 01, the conductive layer 03, the probe base layer 04, and the probes 05 to thereby form an accommodating space for accommodating the sample to be tested.
(96) It is noted in any of the sub-steps S100a (i.e. formation of the pattern of conductive layer 03) and S100b (i.e. formation of the pattern of probe base layer 04) can be realized by a one-time patterning process (i.e. use of a single mask), or by a multi-step process, involving a step of formatting a material layer (i.e. a layer of composition for the conductive layer 03 or a layer of composition for the probe base layer 04) and a step of etching the material layer to thereby form the pattern of the conductive layer 03 and/or the pattern of the probe base layer 04.
(97) In a third aspect, the disclosure provides a method for sample testing using the sample testing apparatus as mentioned above.
(98)
(99) S301: Loading a testing sample in the accommodating space of the detection device in the sample testing apparatus;
(100) S302: Sensing an electrical signal from the detection device via the data line electrically coupled therewith after a time period of reaction; and
(101) S303: Determining that target molecules in the testing sample react with probes in the detection device if a difference between a value of the electrical signal and a standard value is larger than a pre-determined threshold.
(102) The sample testing method utilizing the aforementioned sample testing apparatus have an advantages such as simplicity and low testing noises.
(103) Together, the present disclosure provides a sample testing apparatus, its manufacturing method, and a sample testing method using the sample testing apparatus. The sample testing apparatus includes a plurality of detection devices over a substrate. Each detection device comprises a plurality of electrodes and a plurality of data lines.
(104) Each data line is a multilayer structure and comprises a plurality of film layers. A first film layer in each data line is at a substantially same layer as the plurality of electrodes and has a first composition that is substantially same as the conductive material used for the plurality of electrodes. Other film layers in each data line comprises at least one second film layer having a composition that has a relatively lower electric resistance than the first film layer.
(105) As such, in each of the plurality of data lines having the above mentioned multilayer structure, the first film layer in each data line can be configured to be at a substantially same layer and have a substantially same composition as the plurality of electrodes. The composition for the electrodes and the first film layer of each data line is configured to have a relatively good compatibility to target molecules in the sample, and to have a relatively high electric resistance, and the composition for other film layers of each data line is configured to have a relatively low electric resistance. Thereby, the sample testing apparatus has the following advantageous features: first, the electrodes have a good compatibility with the sample; and second, the data lines have relatively low electric resistance. As such, the testing noise during sample testing can be effectively reduced.
(106) Although specific embodiments have been described above in detail, the description is merely for purposes of illustration. It should be appreciated, therefore, that many aspects described above are not intended as required or essential elements unless explicitly stated otherwise.
(107) Various modifications of, and equivalent acts corresponding to, the disclosed aspects of the exemplary embodiments, in addition to those described above, can be made by a person of ordinary skill in the art, having the benefit of the present disclosure, without departing from the spirit and scope of the disclosure defined in the following claims, the scope of which is to be accorded the broadest interpretation so as to encompass such modifications and equivalent structures.