KR20200069409A - PCB Based Bio-Chip - Google Patents

Abstract

The present invention relates to a PCB-based bio-chip, and more specifically, to a PCB-based bio-chip which can use a PCB including a bio-sensor and an electric circuit to integrate and unify the bio-sensor and the electric circuit. According to the present invention, the conventional technology manufactures a bio-chip by using plastic or glass substrates and thus, has difficulties in adding functionalities for heaters, micro pumps, valves, or the like or integrating a bio-sensor and an electric signal processing circuit, but the present invention has merits where a PCB including a bio-sensor and an electric circuit is used to integrate and unify the bio-sensor and the electric circuit and accordingly, the performance of the bio-chip can be improved. In addition, the present invention has excellent effects where the bio-sensor can be integrated with the bio-chip to directly measure a signal without a reader.

Description

PCB Based Bio-Chip

The present invention relates to a PCB-based biochip, and more particularly, to a PCB-based biochip capable of integrating and integrating a biosensor and an electric circuit using a PCB substrate including a biosensor and an electric circuit.

Currently, disease diagnosis technology using antigen-antibody immune response and genetic test molecular diagnosis is widely used in in vitro diagnostic devices in hospitals. In recent years, diagnostic devices for testing such diseases have developed into field diagnosis devices (POCT, Point of Care and Testing) that can be tested at the site where the patient is located, that is, in the emergency room, hospitalization room, and home. Furthermore, by making these on-site diagnostic devices into one disposable chip, we are researching and developing biochips that can be conveniently inspected by users. The integration of the control circuit can implement various functions on the biochip, and the integration of the signal processing circuit can measure the signal of the biosensor more accurately. For example, if the signal from the sensor is amplified directly from a nearby place without going through an interconnection, noise can be minimized, and initialization and calibration of the sensor signal can be facilitated. However, most biochips currently being studied have a problem in that only some functions are implemented because it is difficult to integrate a biosensor or a circuit.

That is, conventional biochips or lab-on-a-chips generally have biochips made of plastic or glass substrates, and thus have difficulties in adding functionalities such as micro pumps and valves or integrating biosensors and signal processing circuits. The currently developed biochip is mainly made of plastics, which makes fluidics such as chambers and channels to mix, separate, and react reagents, and utilizes glass or silicon substrates to provide simple heaters, pumps, etc. Some features are implemented. However, in order to add better performance and various functionalities, various electronic components must be used. However, it is difficult to mount necessary electronic components in combination with fluidics using a glass substrate.

In addition, in the conventional biochip, the biosensor is not integrated, so the biochip is combined with an external reader to detect the measurement signal. Currently, many biosensors are used in optical, electrochemical, etc. These biosensors require optical components such as photodiodes, image sensors, LEDs, and LDs in the case of optical, and work electrodes, counter electrodes, and reference electrodes in the case of electrochemicals. Electrochemical measuring parts such as are required. These components have been miniaturized due to the development of technology, and thus the applicability to biochip fluidics has increased, but they have not been attempted in existing biochips of plastic or glass substrates. In addition, in a conventional biochip, it is impossible to integrate a control circuit for controlling a heater, a pump, and a sensor and a signal processing circuit for processing a signal from the sensor.

As a prior art, Republic of Korea Patent No. 0598375 relates to a system and method for measuring the properties of biomaterials, and a bio device that emits light by electrochemical action by applying a voltage to an aqueous solution containing a biochip with a fixed gene. ; A power supply unit supplying a voltage to the bio device; A photodetector for detecting light generated from the bio device; A signal processor which converts the light detected by the photodetector into an electrical signal; Disclosed is an analysis unit that analyzes characteristics of a gene with an electrical signal converted by the signal processing unit.

However, the conventional technology such as the patent still manufactures a PCB-based biochip that can be integrated by integrating a biosensor and an electric circuit, or a PCB-based biochip that can directly measure a signal without a reader by integrating the biosensor into a biochip. I had a problem that I could not.

Republic of Korea Registered Patent No. 0598375 (2006.06.30)

Accordingly, an object of the present invention is to provide a PCB-based biochip that can be integrated by integrating a biosensor and an electric circuit by utilizing a PCB substrate including a biosensor and an electric circuit.

Another object of the present invention is to provide a PCB-based biochip that can directly measure a signal without a reader by integrating the biosensor into the biochip.

The PCB-based biochip according to an embodiment of the present invention for achieving the above object may include a biosensor formed inside the multilayer PCB.

In addition, in the PCB-based biochip according to the present invention, it may further include a storage chamber for storing reagents or cleaning solutions formed inside the uppermost layer of the multilayer PCB.

In addition, in the PCB-based biochip according to the present invention, a surface-mounted portion of the lowermost layer of the multilayer PCB may further include a heater that heats the reagent or cleaning solution inside the storage chamber.

In addition, in the PCB-based biochip according to the present invention, it is formed to be connected to the storage chamber, and may further include a channel through which the reagent or washing solution is transferred.

In addition, in the PCB-based biochip according to the present invention, the heater is installed inside the storage chamber, and is characterized in that the reagent or washing solution heated in the chamber is transferred through a channel.

In addition, in the PCB-based biochip according to the present invention, a reaction chamber in which the transferred reagent reacts may be further included.

In addition, in the PCB-based biochip according to the present invention, the biosensor is formed on an intermediate layer of the multi-layer PCB, and is characterized by measuring a reaction signal in the reaction chamber.

In addition, in the PCB-based biochip according to the present invention, the PCB-based biochip has a plurality of storage chambers, and the plurality of storage chambers are connected by channels.

In addition, in the PCB-based biochip according to the present invention, the first storage chamber contains an enzyme, the second storage chamber contains a buffer solution for washing, and the channel of the first storage chamber is a channel of the second storage chamber. It is characterized by being connected.

In addition, in the PCB-based biochip according to the present invention, the third storage chamber includes a substrate solution, the fourth storage chamber includes a washing buffer solution, and the channel of the third storage chamber is the fourth storage chamber. It is characterized by being connected to the channel.

In addition, in the PCB-based biochip according to the present invention, the heater is characterized in that the PTC.

In addition, in the PCB-based biochip according to the present invention, the lowermost layer portion of the multilayer PCB is provided with a circuit for measuring a signal of the biosensor by applying a voltage.

According to the present invention, since the prior art manufactures biochips from plastic or glass substrates, it is difficult to add functionalities such as heaters, micropumps, valves, or to integrate biosensors and electrical signal processing circuits. It is possible to integrate the biosensor and the electric circuit by using a PCB substrate including the electric circuit, and thereby, there is an advantage that the performance of the biochip can be improved.

In addition, the conventional technology could not directly combine general electronic components with fluidics, but the present invention can be combined with fluidics and various electronic components to enable integration into biochips, thereby diversifying biochip functions. Do. That is, various functions can be easily implemented in a bio chip or a lab on a chip (LoC) that is being developed to perform a bio analysis and inspection performed in a hospital or a laboratory by minimizing manual operation on a small chip.

In addition, there is an excellent effect of integrating the biosensor into the biochip to directly measure the signal without a reader.

1 is a schematic diagram showing an inspection step of a conventional electrochemical biosensor.
Figure 2 is a schematic diagram showing a field diagnostic device for a conventional electrochemical measurement.
3 is a schematic view showing a top view of a PCB-based biochip according to the present invention.
4 is a schematic view showing a cross-section of a PCB-based biochip according to the present invention.
5 is a photograph of a PCB biochip manufactured according to an embodiment of the present invention.

Hereinafter, exemplary embodiments disclosed herein will be described in detail with reference to the accompanying drawings, but the same or similar elements are assigned the same reference numbers regardless of the reference numerals, and overlapping descriptions thereof will be omitted. The suffixes "modules" and "parts" for components used in the following description are given or mixed only considering the ease of writing the specification, and do not have meanings or roles distinguished from each other in themselves. In addition, in describing the embodiments disclosed in this specification, detailed descriptions of related known technologies are omitted when it is determined that the gist of the embodiments disclosed in this specification may be obscured. In addition, the accompanying drawings are only for easy understanding of the embodiments disclosed in the present specification, and the technical spirit disclosed in the specification is not limited by the accompanying drawings, and all modifications included in the spirit and technical scope of the present invention , It should be understood to include equivalents or substitutes.

Terms including ordinal numbers such as first and second may be used to describe various components, but the components are not limited by the terms. The terms are used only for the purpose of distinguishing one component from other components.

When an element is said to be "connected" or "connected" to another component, it is understood that other components may be directly connected to or connected to the other component, but there may be other components in between. It should be. On the other hand, when a component is said to be "directly connected" or "directly connected" to another component, it should be understood that no other component exists in the middle.

Singular expressions include plural expressions unless the context clearly indicates otherwise.

In this application, terms such as "comprises" or "have" are intended to indicate the presence of features, numbers, steps, actions, components, parts or combinations thereof described in the specification, but one or more other features. It should be understood that the existence or addition possibilities of fields or numbers, steps, operations, components, parts or combinations thereof are not excluded in advance.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. It will be apparent to those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit and essential features of the present invention.

Example

As an embodiment of the present invention, a field diagnostic device for testing a specific antigen, which is a disease biomarker present in a patient sample of blood or urine, was implemented with a single biochip.

A method of testing the concentration of antigen present in a patient sample using a conventional electrochemical biosensor consists of three steps as shown in FIG. 1. Specifically, first step (a) of reacting with an antigen and a sensor of a blood or urine sample, step 2 (c) of reacting with an antibody labeled with an enzyme reaction catalyst such as alkaline phosphatase (ALP), ascorbic acid 2 (APA) -phosphate) consists of three steps (e) of measuring a signal by an electrochemical method. Between each step, the electrode to which the antigen and antibody have reacted must be washed with a washing solution. This reaction and cleaning is a hassle that the user must do by hand. In order to measure the signal by the electrochemical method in step 3, the working electrode to which the enzyme-catalyst antibody is bound must be immersed in a measurement solution that causes redox reaction together with the counter electrode and the reference electrode. In this state, the current value flowing after applying a specific voltage to the working electrode and the counter electrode is measured. An example of an on-site diagnostic device for electrochemical measurements that enables such measurements is shown in FIG. 2. This on-site diagnostic device consists of an electrode that is a biosensor, a circuit for applying a voltage to the electrode and measuring the current, and a cartridge that stores reagents, cleaning solutions, and measuring solutions.

The present invention removes the hassle of manually reacting and washing step by step of such a field diagnosis device, and implements biosensors, circuits, and cartridges, which are components, in order to realize a biochip that is automatically measured in one chip. Integrated into the controlling chip. In order to integrate all the components of this on-site diagnostic device onto a single chip, a printed circuit board (PCB) that easily integrated a complex circuit onto a substrate was used, and a PCB substrate was processed and used to control the fluid. Design examples of one PCB-based biochip are shown in FIGS. 3 (top view) and 4 (section view). There are four chambers (brown) that serve as cartridges for storing reagents and cleaning solutions, and each chamber has a pump that acts as a heater. The chamber (chamber, green) constituting the pump is made of PCB, and a positive temperature coefficient (PTC) component (red) is mounted on the PCB as a heater in the chamber. The biosensor integrated on the PCB is located in the reaction chamber (yellow, yellow) where reaction and cleaning are performed. To this reaction chamber, the pump transports reagents and washing liquids through channels to automatically react, wash, and measure. The PCB is made of a multi-layer PCB, and a circuit for applying and measuring voltage to an electrode on the lower PCB is integrated.

An example of a PCB-based biochip fabricated in PCB is shown in FIG. 5. In this biochip, the pump chamber was fabricated by processing the PCB, and the chamber for storing reagents and cleaning solutions and the reaction chamber were made of plastic. 5(a) is a PCB substrate in which the heater PTC is surface mounted on the lower PCB substrate and the upper PCB is processed to form a chamber. A biochip produced by bonding a plastic substrate having a chamber and a channel to the substrate is a photograph of FIG. 5B. In this photo, blue is the washing liquid, orange is the reagent and the measuring liquid, and the heater in the upper-right chamber is switched on to show the state in which the washing liquid flows into the reaction chamber while the pump is operating.

According to the present invention, since the prior art manufactures biochips from plastic or glass substrates, it is difficult to add functionalities such as heaters, micropumps, valves, or to integrate biosensors and electrical signal processing circuits. It is possible to integrate the biosensor and the electric circuit by using a PCB substrate including the electric circuit, and thereby, there is an advantage that the performance of the biochip can be improved. In addition, there is an excellent effect of integrating the biosensor into the biochip to directly measure the signal without a reader.

Meanwhile, the above detailed description should not be construed as limiting in all respects and should be considered as illustrative. The scope of the invention should be determined by rational interpretation of the appended claims, and all changes within the equivalent scope of the invention are included in the scope of the invention.

Claims (12)

A biosensor formed inside the multilayer PCB;
PCB-based biochip comprising a.
According to claim 1,
A storage chamber for storing reagents or cleaning solutions formed inside the uppermost layer of the multilayer PCB;
PCB-based biochip further comprising a.
According to claim 1,
A heater mounted on the lowermost layer of the multi-layer PCB to heat the reagent or cleaning solution inside the storage chamber;
PCB-based biochip further comprising a.
According to claim 1,
It is formed to be connected to the storage chamber, a channel through which the reagent or washing solution is transferred;
PCB-based biochip characterized in that it further comprises.
The method of claim 4,
The heater is installed inside the storage chamber, PCB-based biochip, characterized in that to transfer the reagent or cleaning solution heated in the chamber through a channel.
The method of claim 5,
A reaction chamber in which the transferred reagent reacts;
PCB-based biochip further comprising a.
According to claim 1,
The biosensor is formed on the intermediate layer of the multi-layer PCB, PCB-based biochip, characterized in that for measuring the reaction signal in the reaction chamber.
According to claim 1,
The PCB-based biochip has a plurality of storage chambers, and the plurality of storage chambers are PCB-based biochips characterized in that they are connected by channels.
The method of claim 8,
A PCB-based biochip characterized in that the first storage chamber contains an enzyme, the second storage chamber contains a buffer solution for washing, and a channel of the first storage chamber is connected to a channel of the second storage chamber.
The method of claim 8,
The third storage chamber includes a substrate solution, the fourth storage chamber includes a washing buffer solution, and the channel of the third storage chamber is a PCB-based biochip, characterized in that connected to the channel of the fourth storage chamber.
According to claim 3,
The heater is a PCB-based biochip, characterized in that PTC.
According to claim 3,
PCB-based biochip, characterized in that it comprises a circuit for measuring the signal of the biosensor by applying a voltage to the bottom layer of the multilayer PCB.

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