The present invention relates to a phoresis device (TFT on glass platform for biological applications).
In recent years, there has been actively developed a technique of performing, on a target object (sample) such as a cell, various manipulations such as a manipulation of moving the sample.
For example, Patent Literature 1 discloses a device that can move a sample by electrowetting on dielectric (EWOD).
Patent Literature 2 discloses a device that can move a sample by dielectrophoresis (DEP).
[Patent Literature 1]
[Patent Literature 2]
However, Patent Literatures 1 and 2 neither disclose nor suggest a technical idea of realizing, with use of a thin film transistor (TFT) substrate, a phoresis device for moving a target object by dielectrophoresis.
Therefore, with the inventions disclosed in Patent Literatures 1 and 2, it is not possible to realize, with use of a thin film transistor substrate, a phoresis device for moving a target object by dielectrophoresis.
The present invention has been made in view of the above problem, and an object of the present invention is to realize, with use of a thin film transistor substrate, a phoresis device for moving a target object by dielectrophoresis.
In order to attain the above object, a phoresis device in accordance with an embodiment of the present invention is a phoresis device for moving a target object by dielectrophoresis, the phoresis device including: a thin film transistor substrate which supports the target object and which is configured to form an electric field that causes the dielectrophoresis, the thin film transistor substrate including a plurality of transistors, the target object being moved through application of a voltage to part of the plurality of transistors of the thin film transistor substrate.
According to a phoresis device in accordance with an embodiment of the present invention, it is possible to realize, with use of a thin film transistor substrate, a phoresis device for moving a target object by dielectrophoresis.
(a) through (c) of
(a) through (e) of
(a) and (b) of
(a) and (b) of
(a) through (c) of
(a) of
(a) of
(a) and (b) of
(a) and (b) of
(a) of
(a) of
The following description will discuss Embodiment 1 of the present invention with reference to
(Outline of Phoresis Device 1)
The phoresis device 1, as described later, serves to move a target object (e.g., a cell) by dielectrophoresis.
With the phoresis device 1, it is possible to arrange a cell (i.e., the target object) at an intended position by dielectrophoresis. This makes it possible to prevent the cell from adhering to the surface of the TFT substrate 10. Moreover, the phoresis device 1 also makes it possible to perform various manipulations (described later), such as chemical treatment and electrical stimulation, on the cell that has been arranged at the intended position by dielectrophoresis.
In the case of culturing cells on the TFT substrate 10, by performing dielectrophoresis in advance, it is possible to prevent different kinds of cells from being mixed with each other before the cell culturing. This makes it possible to suitably culture cells on the TFT substrate 10.
Moreover, it is possible to use dielectrophoresis to control the direction of the axon of the nerve cell T2 with respect to the muscle cell T1.
The target object of dielectrophoresis is, however, not limited to a cell, and can be any object (e.g., a particle) that can be moved by dielectrophoresis.
(TFT Substrate 10)
The TFT substrate 10 serves to form an electric field that causes dielectrophoresis by which the target object is moved. The TFT substrate 10 also serves as a supporting member that supports the target object. In the present embodiment, some members of a TFT liquid crystal panel for use in a display device are used as the TFT substrate 10 (see
The TFT liquid crystal panel, as shown in
Between the upper glass substrate and the lower glass substrate, the TFT liquid crystal panel includes polarizing plates, a color filter, a liquid crystal, a spacer, and a TFT layer. Descriptions of these members except for the TFT layer are, however, omitted because they are not related to the present embodiment.
On the TFT substrate 10, the gate electrode of each TFT is connected to a corresponding one of a plurality of first wirings, which are arranged in a first direction so as to be parallel to each other. The first wirings can alternatively be referred to as gate wirings, because they are connected to respective gate lines GL.
Meanwhile, the source electrode of each TFT is connected to a corresponding one of a plurality of second wirings, which are arranged in a second direction so as to be parallel to each other. The second direction can be, for example, a direction perpendicular to the above-described first direction. The second wirings can alternatively be referred to as source wirings, because they are connected to respective source lines SL.
The plurality of TFTs are, as shown in
The drain electrode of each TFT is connected to a corresponding one of pixel electrodes, which are arranged on the TFT substrate 10 in a matrix manner. This makes it possible to switch each of the pixel electrodes, which are connected to the respective drain electrodes, between the ON-state and the OFF-state by adjusting the voltages to be applied to the corresponding gate line GL and source line SL.
For example, in a case where voltages are applied to a single gate line GL and a single source line SL, a TFT 11a (transistor), which is arranged at the intersection between the gate wiring connected to the single gate line GL and the source wiring connected to the single source line SL, is switched to the ON-state (see
In the case of
As such, by switching part of the plurality of TFTs of the TFT substrate 10 to the ON-state, it is possible to form an electric field (i.e., a non-uniform electric field) that causes dielectrophoresis by which the target object placed on the TFT substrate 10 is moved.
Each of the gate wirings and the source wirings of the TFT substrate 10 can be made of, for example, indium tin oxide (ITO). By using ITO, it is possible to make those wirings transparent.
Alternatively, in order to reduce the electrical resistance of the gate wirings and the source wirings, it is possible to use an opaque metal material (e.g., Al) for those wirings. This point will be later described in a modified example. Each of the pixel electrodes can also be made of ITO.
(a) through (c) of
The TFT substrate 10, as shown in each of (a) through (c) of
The COM electrodes 110c each can be grounded so as to stabilize the electric potential difference between the ITO electrodes 110a. The COM electrodes 110c are, however, not essential for the phoresis device 1 to perform dielectrophoresis.
The ITO electrodes 110a each do not have a property that adversely affects a cell which serves as the target object in a case where the cell is brought into contact with any of the ITO electrodes 110a. It is therefore possible to place a cell (and a liquid containing the cell), which is targeted for dielectrophoresis, directly on the surface(s) of the ITO electrode(s) 110a.
In order to prevent the chemical change from occurring on the surfaces of the ITO electrodes when voltages are applied to the ITO electrodes 110a, it is possible to apply an appropriate coating to the surfaces of the ITO electrode 110a. For example, the ITO electrodes 110a can be coated with an insulating film made of a material such as SiO2, SiNx, or polyimide.
(Chamber 20)
The chamber 20, which is arranged on the TFT substrate 10, is a member that restricts the range of movement of the target object. The chamber 20 is produced preferably as a member having a certain light-transmitting property.
Examples of the material for the chamber 20 include polydimethyl siloxane (PDMS), epoxy resin (particularly, SU-8), polymethyl methacrylate (PMMA), polyvinylidene difluoride (PVDF), glass, and quartz.
By using PDMS as the material for the chamber 20, it is possible to particularly facilitate production of the chamber 20. This is because a chamber 20 made of PDMS can be patterned by mixing two kinds of material liquids, curing the resultant mixture, and shaping (transferring) the cured material on (to) a mold pattern. Therefore, by using PDMS as the material for the chamber 20, it is possible to easily produce the chamber even in a case where the chamber 20 is of a relatively large size.
PDMS is particularly suitable in a case where a cell serves as the target object because, for example, (i) it has excellent adhesion to the substrate, (ii) it has excellent chemical resistance, (iii) it does not emit autofluorescence, and (iv) it has biocompatibility.
Meanwhile, in a case where SU-8 is used as the material for the chamber 20, it is possible to form the chamber 20 by a light exposure process. Therefore, SU-8 is particularly suitable in a case where precise alignment is required for the chamber 20.
The chamber 20 is capable of storing a liquid that contains the target object. The chamber 20 can have, for example, a rectangular shape. In such a case, the chamber 20 can be a frame-like member having no bottom.
In a case where the chamber 20 has a bottom, the chamber 20 can have a space therein for retaining a liquid. In such a case, the chamber 20 can have an injection hole H via which a liquid is injected into the space from the outside.
Provision of the chamber 20 allows the phoresis device to handle a liquid that contains the target object. This is because the chamber 20 makes it possible to prevent the liquid from leaking out of the TFT substrate 10, and in turn makes it possible to prevent the liquid from adversely affecting other members (particularly, electrical members such as the substrate 30).
Provision of the chamber 20 therefore allows the target object contained in the liquid to be more efficiently moved by dielectrophoresis. Provision of the chamber 20 also allows for reduction in strength of the electric field that causes dielectrophoresis. This makes it possible to reduce electrical stress applied to the target object.
The phoresis device 1, however, does not necessarily include the chamber 20. In a case where efficient movement of the target object is not required or where the target object is highly resistant to electrical stress, it is possible to place the target object directly on the surface of the TFT substrate 10 and perform dielectrophoresis on the target object thus directly placed.
Note that, in order to further enhance the efficiency of moving the liquid, it is possible to provide, in the chamber 20 as appropriate, a micro-channel (micro-flow path) via which the flow of a liquid can be controlled. In a case where a plurality of micro-channels are provided, it is also possible to facilitate the manipulation of removing, from the liquid, unnecessary components other than the target object.
(Other Members)
Next, other members of the phoresis device 1 will be described below with reference to
In the present embodiment, the substrate 30 is arranged so as to support the TFT substrate 10. Although not shown in the drawings, for example, by hollowing out a portion of the substrate 30 which portion overlaps with the TFT substrate 10, it is possible to observe the TFT substrate 10 from below even in a case where an opaque printed substrate is used as the substrate 30.
A direct-current (DC) power source 41 is, as shown in
Meanwhile, an alternating-current (AC) power source 42 is connected to the source lines SL (in other words, source wirings) via the substrate 30. The AC power source 42 generates a certain AC voltage waveform (e.g., a sinusoidal voltage or a pulse waveform voltage), and is preferably capable of adjusting the frequency and the amplitude of the certain AC voltage waveform. For example, a function generator can be used as the AC power source 42.
The above arrangement makes it possible to (i) apply a DC voltage generated by the DC power source 41 to the gate electrode of a certain TFT and (ii) apply an AC voltage generated by the AC power source 42 to the source electrode of the certain TFT.
A simulating circuit (artificial network) 43 is connected to the source lines SL via the substrate 30. The simulating circuit 43 serves to generate an AC voltage (e.g., the voltage waveform shown in (b) of
The simulating circuit 43 can be realized by, for example, a large scale integrated (LSI) device. The AC voltage generated by the simulating circuit 43 is applied to the source electrode of a certain TFT. Note that the simulated stimulation will be described later in detail.
(Chemical Treatment)
At least the muscle cell T1 or the nerve cell T2 can be subjected to a chemical treatment. The chemical treatment can be a treatment that is performed for the purpose of giving chemical stimulation to the muscle cell T1 or the nerve cell T2.
As described earlier, the chemical treatment can be performed after the muscle cell T1 and the nerve cell T2 are arranged at respective certain positions by dielectrophoresis. Note that a chemical solution with which the chemical treatment is performed can be injected into the chamber 20 via the injection hole H.
For example, in order to give chemical stimulation to the muscle cell T1, it is possible to perform a chemical treatment on the muscle cell T1 with use of GM6, which is a medicine for amyotrophic lateral sclerosis (ALS) manufactured by GENERVON.
Meanwhile, on the nerve cell T2, it is possible to perform a chemical treatment with use of a neuro peptide, which is a chemical substance that stimulates the nerve cell T2.
By performing a chemical treatment CT, it becomes possible to investigate (i) an activated protein C in a specific disease (e.g., ALS) or (ii) other methods of treating a muscle disorder.
(Study on Frequency of AC Voltage Used in Dielectrophoresis)
Prior to an experiment of dielectrophoresis performed with use of the phoresis device 1 in accordance with the present embodiment, the inventors of the present invention conducted a study concerning the frequency of the AC voltage used in dielectrophoresis. That is, by applying the AC voltage to an experimental circuit on which a striped pattern of ITO was arranged, the inventors of the present invention checked how the frequency of the AC voltage is related to the movement speed (i.e., the phoresis speed) of the target object.
As is clear from
The graph of
The graph of
Note that a force FDEP, which is applied to the target object during dielectrophoresis, is known to be expressed by the following Equation (1):
In Equation (1), r denotes the radius of the target object, εp denotes the dielectric constant of the target object, em denotes the dielectric constant of the liquid that contains the target object, Erms denotes the rms value of the electric field applied to the target object, * (asterisk) is a symbol representing a complex number, and Re is a symbol representing the real part of the complex number.
From Equation (1), it is understood that the force FDEP applied to the target object also depends on the frequency of the electric field applied to the target object. The graph of
(a) through (e) of
As is clear from (a) through (e) of
However, as is clear from Equation (1), the frequency at which dielectrophoresis becomes particularly effective depends on the dielectric constant ep of the target object and the dielectric constant em of the liquid (in other words, the frequency depends on the kinds of the target object and of the liquid). As such, in a case where the target object is something (e.g., a cell) other than micro-beads, dielectrophoresis may become particularly effective at a frequency other than 500 kHz.
In view of the above, considering the margin of a settable frequency range and the like, the inventors of the present invention set, to 100 kHz, the frequency of the AC voltage used to perform dielectrophoresis in the phoresis device 1. Note, however, that a frequency other than 100 kHz can be used to perform dielectrophoresis in the phoresis device 1, depending on the kind of the target object and the like.
In a case where a cell serves as the target object, an excessively high peak value of the AC voltage may adversely affect the cell. The inventors of the present invention then set, to approximately 4 V, the peak value of the AC voltage used to perform dielectrophoresis in the phoresis device 1.
(Experimental Examples of Dielectrophoresis Performed with Use of Phoresis Device 1)
Next, experimental examples of dielectrophoresis performed in the phoresis device 1 will be described below with reference to
(a) of
As is clear from (a) of
That is, it was confirmed that, on the TFT layer on which a non-uniform electric field has been formed, the micro-beads move from a position with high electrical potential towards a position with low electrical potential. As such, it was confirmed that negative dielectrophoresis occurs in a case where micro-beads serve as the target object.
(b) of
As is clear from (b) of
As described above, the inventors of the present invention newly conceived the technical idea of performing dielectrophoresis of the target object with use of the TFT substrate 10, and consequently realized the phoresis device 1. Note that, from Equation (1) provided above, it is understood that the polarity of dielectrophoresis depends on the dielectric constant εp of the target object and the dielectric constant εm of the liquid.
(Examples of Result of Optical Observation in Phoresis Device 1)
According to the phoresis device 1 in accordance with the present embodiment, the TFT substrate 10 has a light-transmitting region. It is therefore possible to move the target object by dielectrophoresis as well as to conduct optical observation of the target object. For example, the observer can observe, with the naked eyes or with use of an optical microscope, movement of the target object that is moved by dielectrophoresis.
By producing the chamber 20 as a transparent member, it is possible to conduct optical measurement of the target object even in a case where the phoresis device 1 includes the chamber 20.
(b) of
The observation results illustrated in (a) and (b) of
The phoresis device 1 makes it possible to perform dielectrophoresis of the target object and to allow the target object to be subjected to optical measurement. Therefore, with the phoresis device 1, the observer can easily check whether the result of optical measurement of the target object is consistent with the result of electrical measurement of the target object. Moreover, the observer can also adjust, as appropriate, the condition of electrical measurement with reference to the result of optical measurement.
(Examples of Certain Manipulation of Target Object)
The phoresis device 1 can also form a second electric field, which differs from the electric field that causes dielectrophoresis by which the target object is moved, by (i) adjusting the voltage to be applied to the gate electrode of a TFT (i.e., the voltage to be generated by the DC power source 41) and (ii) adjusting the voltage to be applied to the source electrode of the TFT (i.e., the voltage to be generated by the AC power source 42). The second electric field corresponds to a certain manipulation of the target object other than dielectrophoresis.
Examples of the manipulation of the target object other than dielectrophoresis will be described below with reference to
Note that the manipulations shown in (a) through (c) of
For simplification, the gate lines GL and the source lines SL are not shown in (a) through (c) of
(a) of
(b) of
(c) of
(Experimental Example of Electroporation)
The inventors of the present invention performed electroporation on myeloma cells as an experimental example. The experimental example will be described below with reference to
(a) of
In the present experiment, a fluorescein diacetate (FDA) was used as the fluorescent marker for distinguishing living cells, and a propidium iodide (PI) was used as the fluorescent marker for distinguishing dead cells.
(b) of
In a case where the cell membrane of a living cell is perforated with a hole by electroporation, the PI enters a myeloma cell (i.e., the living cell) via the hole. Note that the PI cannot enter a living cell having no hole. In the myeloma cell which has been electroporated, the fluorescent marker reacts with the core of the myeloma cell. As a result, the myeloma cell is colored pale orange that is a mixed color of green and red.
As such, in the present experiment, it was possible to identify cells colored pale orange as electroporated myeloma cells. For convenience, in (b) of
Meanwhile, another experiment was conducted as in the above experiment except that the amplitude of the pulse was 6 V. In this experiment, all myeloma cells were confirmed to be colored red. That is, it was confirmed that the myeloma cells completely die in a case where the amplitude of the pulse is 6 V.
(a) of
(c) of
(Case where TFT Substrate 10 Serves as Sensor)
According to the phoresis device 1 in accordance with the present embodiment, it is possible to cause at least some portions of the TFT substrate 10 to serve as various sensors.
In the example shown in
The ISFET sensor S1 serves to detect ion sensitive electrical potential. By causing at least part of the TFT substrate 10 to serve as the ISFET sensor, it is possible to detect swaps of a certain kind of ions (e.g., calcium ions, sodium ions, or potassium ions) in the target object. This makes it possible to check the activity level (life and death) of the target object.
The resistive sensor S2 serves to detect electrical resistance (R). By causing at least part of the TFT substrate 10 to serve as the resistive sensor, it is possible to detect whether the target object is present or absent at the position of the at least part of the TFT substrate 10.
The electrostatic capacitive sensor S3 serves to detect electrostatic capacitance (C). By causing at least part of the TFT substrate 10 to serve as the electrostatic capacitive sensor, it is possible to detect whether the target object is present or absent at the position of the at least part of the TFT substrate 10.
The impedance sensor S4 serves to detect impedance (Z). By causing at least part of the TFT substrate 10 to serve as the impedance sensor, it is possible to detect whether the target object is present or absent at the position of the at least part of the TFT substrate 10, as well as to check the activity level of the target object.
As such, by causing certain portions of the TFT substrate 10 to serve as various sensors, it is possible to detect, in the certain portions of the TFT substrate 10, (i) whether the target object is present or absent and (ii) the condition of the target object. It is therefore possible to detect, at an arbitrary position on the TFT substrate 10, (i) whether the target object is present or absent and (ii) the condition of the target object.
(Impedance Sensor)
Next, the fundamental concept of the impedance sensor in accordance with the present embodiment will be described below with reference to
Here, electrostatic capacitance is formed between pixel electrodes of the TFT substrate 10. The alternating current therefore flows, via the electrostatic capacitance formed between the pixel electrode in the ON-state and an adjacent pixel electrode which is adjacent to the pixel electrode in the ON-state, into the TFT that corresponds to the adjacent pixel electrode. The alternating current is then outputted from the source wiring that corresponds to the adjacent pixel electrode.
Note that, in the TFT that corresponds to a pixel electrode in the OFF-state, the electric current flowing from another pixel electrode in the OFF-state is ignorable because the resistance between the source and the drain is extremely large.
Therefore, in the TFT substrate 10, a measurement system (circuit network) is formed in which (i) an AC voltage V*, which is to be applied to the source wiring of the TFT that corresponds to a pixel electrode in the ON-state, is regarded as an input signal and (ii) an alternating current I*, which is to be outputted from the source wiring that corresponds to the TFT of an adjacent pixel electrode which is adjacent to the pixel electrode in the ON-state, is regarded as an output signal. Here, * (asterisk) is a symbol representing a complex number.
Impedance Z of the measurement system is expressed as Z=V*/I*. Since the AC voltage V* is known, it is possible to calculate the impedance Z by making an arrangement such that the alternating current I* is detectable in at least part of the TFT substrate 10. In other words, it is possible to cause the at least part of the TFT substrate 10 to serve as an impedance sensor. The impedance Z can be measured by use of a device such as an LCR meter.
Moreover, by arranging the measurement system so that only the real part of the impedance Z is measurable, it is possible to cause at least part of the TFT substrate 10 to serve as a resistive sensor. Meanwhile, by arranging the measurement system so that only the imaginary part of the impedance Z is measurable, it is possible to cause at least part of the TFT substrate 10 to serve as an electrostatic capacitive sensor.
In contrast, because the cytoplasm includes an electrolyte, the cytoplasm can be regarded as having not only electrostatic capacitance but also electrical resistance. Accordingly, the cytoplasm is expressed as an RC parallel circuit. Therefore, it can be understood that the cell T has certain impedance that is formed by the circuit shown in
As such, in a case where the cell T is placed as shown in
Accordingly, the alternating current I* in the case of
Note that, in a case where at least part of the TFT substrate serves as an impedance sensor, the pixel electrodes in the region of the at least part of the TFT substrate are sequentially switched to the ON-state. By thus conducting measurement of the region where the cell T is placed, it is possible to map the position and the condition of the cell T.
(a) of
(b) of
As such, in a case where at least part of the TFT substrate 10 serves as an impedance sensor, a frequency suitable for measurement is set as appropriate depending on the kind of object subject to impedance measurement.
(Isfet Sensor)
In this experiment, the ISFET sensor was used as a pH sensor, and pH measurement was conducted on three kinds of liquids, namely, (i) a borate pH standard solution (pH=9), (ii) pure water (pH=7), and (iii) a phthalate pH standard solution (pH=4).
(a) of
Therefore, if the correspondence between the gate voltage and the pH is known, the pH of a liquid can be calculated from a measured drain current. In the present experiment, the correspondence between the gate voltage and the pH was expressed, by using the experimental data obtained in advance, as a polynomial “y=0.0157x2+0.0717x+7.664” where x denotes the pH and y denotes the gate voltage.
(b) of
That is, an appropriate pH is calculated for each of the borate pH standard solution and the phthalate pH standard solution. Note that, because pure water absorbs CO2, the pH of pure water decreases during the experiment. As a result, the pH of pure water is calculated to be a value lower than pH=7.
(Examples of Electrical Stimulation)
As described earlier, the AC power source 42 can generate a pulsed voltage waveform, and the simulating circuit 43 can generate a voltage signal that serves as simulated stimulation. Electrical stimulation will be described below with reference to
(a) of
(b) of
It can be understood that the simulated stimulation is electrical stimulation that simulates the biological stimulation given to the nerve cell T2 more precisely than the pulse stimulation. Using the simulated stimulation enables a more precise experiment and less electrical stress to the nerve cell T1, in comparison with using the pulse stimulation.
The simulating circuit 43 can also generate a voltage waveform that simulates the membrane potential of the motor neuron connected to the muscle cell T1. Note that this motor neuron can be cultured on the TFT substrate 10.
(Effect of Phoresis Device 1)
As described above, according to the phoresis device 1 in accordance with the present embodiment, it is possible to realize, with use of the TFT substrate 10, a phoresis device for moving a target object (e.g., a cell) by dielectrophoresis. Moreover, by using the TFT substrate 10 having a light-transmitting region, it is possible to move the target object by dielectrophoresis as well as to allow the target object to be subjected to optical measurement.
Moreover, with the phoresis device 1 in accordance with the present embodiment, it is possible to form a second electric field, which differs from the electric field that causes dielectrophoresis by which the target object is moved, with use of the plurality of TFTs of the TFT substrate 10. By forming the second electric field, it is possible to perform a certain manipulation (e.g., electrical stimulation, electroporation, or cell fusion) of the target object other than dielectrophoresis.
Moreover, by causing at least some portions of the TFT substrate 10 to serve as various sensors (e.g., the ISFET sensor, the resistive sensor, the electrostatic capacitive sensor, and the impedance sensor), it is possible to detect, at the positions at which the various sensors are located, (i) whether the target object is present or absent and (ii) the condition of the target object.
In a phoresis device in accordance with an embodiment of the present invention, the arrangement of the gate wirings and the source wirings on the TFT substrate is not limited to that of Embodiment 1. A modified example of the TFT substrate will be described below with reference to
Next, the advantage brought about by the TFT substrate 10v will be described below with reference to
Note that
According to the TFT substrate 10, the opaque gate wirings and the opaque source wirings are arranged so as to overlap with the edges of the pixel electrodes (see (a) of
In contrast, according to the TFT substrate 10v, the opaque gate wirings and the opaque source wirings are arranged so as not to overlap with the edges of the pixel electrodes (see (b) of
The TFT substrate 10v therefore makes it possible to conduct optical observation of the cell T even in a case where an opaque metal material such as Al is used to reduce the electrical resistance of the gate wirings and the source wirings. The TFT substrate 10v is beneficial because, in a case where dielectrophoresis is performed, a relatively large number of target objects may move to the vicinities of boundaries between the pixel electrodes.
The following description will discuss another embodiment of the present invention with reference to
According to the phoresis device 2, the chamber 25 includes a first chamber 26a (restricting member) and a second chamber 26b (restricting member). The first chamber 26a restricts the range of movement of a liquid containing a muscle cell T1. The second chamber 26b restricts the range of movement of a liquid containing a nerve cell T2.
The first chamber 26a has injection holes H via which a liquid is injected into the first chamber 26a from the outside of the chamber 25. Similarly, the second chamber 26b has injection holes H via which a liquid is injected into the second chamber 26b from the outside of the chamber 25.
The first chamber 26a and the second chamber 26b are spaced from each other so as not to communicate with each other. It is therefore possible to separate the liquids so that the liquid stored in the first chamber 26a is not mixed with the liquid stored in the second chamber 26b.
According to the phoresis device 2, by providing a plurality of chambers (the first chamber 26a and the second chamber 26b), it is possible to perform dielectrophoresis and a certain manipulation individually on the muscle cell T1 and the nerve cell T2, which are contained in the respective liquids thus separated from each other. This further improves the convenience of the phoresis device.
Note that, even in a case where a phoresis device in accordance with an embodiment of the present invention includes a plurality of restricting members, the configuration of the plurality of restricting members is not limited to that of Embodiment 2. A modified example of the restricting member will be described blow with reference to
The chamber 25v has, as shown in
Each of the first chamber 26av, the second chamber 26bv, and the third chamber 26cv has injection holes H via which a liquid is injected thereinto from the outside of the chamber 25v.
Moreover, the chamber 25v includes (i) micro-flow paths MF1 which connect the first chamber 26av with the second chamber 26bv and (ii) micro-flow paths MF2 which connect the second chamber 26bv with the third chamber 26cv. Note that each of the micro-flow paths MF1 and MF2 can have a width of the order of several micrometers.
By providing the micro-flow paths MF1 and MF2, it is possible to connect the first chamber 26av, the second chamber 26bv, and the third chamber 26cv.
For example, the chamber 25v is suitably used to culture the cells contained in the liquids within the individual chambers and then mix the liquids within the chambers with each other. Furthermore, according to the chamber 25v, it is also possible to introduce axons of nerve cells from the chamber in which the nerve cells are stored (e.g., from the first chamber 26av) to the chamber in which muscle cells are stored (e.g., to the second chamber 26bv).
The following description will discuss another embodiment of the present invention with reference to
The microscope 51 is an optical observation device that serves to facilitate optical observation of a target object in the phoresis device 1. The microscope 51 can be manually operated by the observer. The microscope 51 can be, for example, an inverted microscope for observing the target object from the substrate 30 side, or an erected microscope for observing the target object from the chamber 20 side.
The microscope 51 is preferably an inverted microscope. In a case where the microscope 51 is an inverted microscope, it is possible to more easily observe the target object at a high magnification, because no chamber 20 exists between the microscope 51 and the target object.
The digital camera 52 is an optical observation device that serves to further facilitate the optical observation of the target object in the phoresis device 1. The operation of the digital camera 52 is controlled by the control device 60. Therefore, with the digital camera 52, it is possible to conduct optical observation of the target object (i.e., capture an image of the target object) without a need for the observer to make any manual operation.
The control device 60 is a member that comprehensively controls the operations of the digital camera 52 and the phoresis device 1. The control device 60 can be, for example, a personal computer (PC). The control device 60 is connected to the digital camera 52 and a substrate 30.
With the control device 60, it is therefore possible to control the operation of each member (e.g., the DC power source 41, the AC power source 42, and the like) of the phoresis device 1 via the substrate 30. This makes it possible for the user to easily perform dielectrophoresis and various manipulations of the target object via the control device 60.
(Object of Observation System 100)
The observation system 100 is intended to realize a platform that allows for in-vitro analysis for the researches that place importance on cell-to-cell interactions.
The observation system 100 can be used to conduct, for example, (i) investigation of disease processes or (ii) research on treatment for a disease such as ALS or myopathy.
According to the phoresis device 1, it is possible to give electrical stimulation only to a muscle cell or a nerve cell that has been arranged at a specific position on a TFT substrate 10. This makes it possible to culture a complete muscle unit (a muscle cell with a motor neuron).
With the observation system 100, it is also possible to treat more than two kinds of cells as experimental objects, so as to build a model that is more similar to a living body. For example, in order to facilitate the research on cell-to-cell interactions, it is possible to introduce a sensory receptor (e.g., a cell that senses heat), place the cell on the TFT substrate 10, and connect the cell with a nerve cell.
[Recap]
A phoresis device in accordance with a first aspect of the present invention is a phoresis device (1) for moving a target object (e.g., cell T) by dielectrophoresis, the phoresis device including: a thin film transistor substrate (TFT substrate 10) which supports the target object and which is configured to form an electric field that causes the dielectrophoresis, the thin film transistor substrate including a plurality of transistors (TFT 11a), the target object being moved through application of a voltage to part of the plurality of transistors of the thin film transistor substrate.
According to the above configuration, it is possible to realize, with use of a TFT substrate, a phoresis device for moving the target object by dielectrophoresis.
The phoresis device in accordance with a second aspect of the present invention is preferably configured such that, in the first aspect of the present invention, the thin film transistor substrate has a light-transmitting region.
According to the above configuration, by using the TFT substrate having a light-transmitting region, it is possible to move the target object by dielectrophoresis as well as to allow the target object to be subjected to optical measurement.
The phoresis device in accordance with a third aspect of the present invention is preferably configured to further include, in the first or second aspect of the present invention, a restricting member (chamber 20), arranged on the thin film transistor substrate, which restricts a range of movement of the target object.
According to the above configuration, the restricting member is provided on the TFT substrate. This allows the phoresis device to handle a liquid that contains the target object.
The phoresis device in accordance with a fourth aspect of the present invention is preferably configured such that, in the third aspect of the present invention, the restricting member is made of polydimethyl siloxane, epoxy resin, polymethyl methacrylate, polyvinylidene difluoride, glass, or quartz.
According to the above configuration, it is possible to produce the restricting member as a transparent member. This makes it possible to allow the target object to be subjected to optical measurement even in a case where the phoresis device includes the restricting member.
The phoresis device in accordance with a fifth aspect of the present invention is preferably configured such that, in any one of the first through fourth aspects of the present invention, at least part of the thin film transistor substrate serves as at least one of an ion sensitive field effect transistor (ISFET sensor S1), a resistive sensor (S2), an electrostatic capacitive sensor (S3), and an impedance sensor (S4).
According to the above configuration, the TFT substrate serves as the above sensors. This makes it possible to evaluate the presence/absence of the target object or the condition of the target object. For example, in a case where the target object is a cell, it is possible to determine the activity level (life or death) of the cell by measuring the impedance of the cell with use of the impedance sensor.
The phoresis device in accordance with a sixth aspect of the present invention is preferably configured such that, in any one of the first through fifth aspects of the present invention, the thin film transistor substrate is configured to form a second electric field, which differs from the electric field that causes the dielectrophoresis by which the target object is moved; and the second electric field corresponds to a certain manipulation of the target object other than the dielectrophoresis.
According to the above configuration, the second electric field is formed. This makes it possible to perform a certain manipulation of the target object other than dielectrophoresis.
The phoresis device in accordance with a seventh aspect of the present invention is preferably configured such that, in the sixth aspect of the present invention, the target object is a cell; and the certain manipulation is a manipulation of electrically stimulating the cell, a manipulation of electroporating the cell, or a manipulation of performing cell fusion of a plurality of the cells.
The above configuration makes it possible to perform a manipulation of electrically stimulating the cell, a manipulation of electroporating the cell, or a manipulation of performing cell fusion of a plurality of cells.
The present invention is not limited to the embodiments, but can be altered by a skilled person in the art within the scope of the claims. The present invention also encompasses, in its technical scope, any embodiment derived by combining technical means disclosed in differing embodiments. Further, it is possible to form a new technical feature by combining the technical means disclosed in the respective embodiments.
Number | Date | Country | Kind |
---|---|---|---|
2015-141625 | Jul 2015 | JP | national |
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/JP2016/070656 | 7/13/2016 | WO | 00 |