JP4455917B2 - Scientific apparatus and separation method - Google Patents

Description

  The present invention relates to a scientific apparatus and a separation method for performing a microchemical process.

The microchemical process is a process using physical phenomena and chemical phenomena that are expressed in a microchannel having a width of several μm to several hundred μm created by using a micromachining technique. Features of downsizing the flow path include the following. That is,
(1) The surface area per unit volume is very large. (2) Since the Reynolds number is small, laminar flow can be easily achieved. (3) Synthesis in a very small amount is possible. Due to the above features, the following matters are expected. That is,
(1) Temperature control can be performed precisely and efficiently (2) Reaction at the interface can be performed efficiently (3) Efficient mixing can be performed.

  In recent years, Gino V. A new chromatographic separation technique called Shear-Driven Chromatography (SDC) has been reported by Baron et al. The reported SDC apparatus is a flat plate type device having a thin-film adsorbent, and the eluent in the micro space is made to flow by using a shearing force instead of a conventionally used pressure or electric force. An outline of the SDC device is shown in FIGS. 44 (a) and 44 (b).

  The stationary phase (adsorbent) is arranged in a thin plate shape. By moving the moving wall, the mobile phase liquid (eluent) flows due to its viscosity. The mobile phase (channel) thickness and the stationary phase thickness are both micro-sized, and each component of the sample is separated in this micro space. Since it is a Couette flow by shear drive, the mobile phase average flow velocity is half of the moving wall velocity.

  In the latest HPLC (high-speed chromatography High Pressure Chromatography or high-performance chromatography High Performance Chromatography), a small column tube with a diameter of several mm and a porous adsorbent particle with a particle size of several μm is used. As the particle size is reduced, the interfacial area per unit volume increases and high chromatographic separation performance is expected. However, the smaller the particle size, the greater the pressure loss in that column, making it difficult to operate at high speeds in terms of pump performance and column tube strength. In pressure-driven chromatography (Pressure-driving Chromatography PDC), pressure is applied at the column inlet (eluent supply port), and in comparison with driving the eluent, SDC applies shear force throughout the eluent flow direction, It is possible to drive the eluent. Therefore, the greatest feature of SDC is that it avoids technical limitations due to pressure drop in PDC.

  However, the SDC apparatus introduced here cannot be used for continuous separation.

  Several cross-flow type adsorption separation apparatuses have been developed for the purpose of continuous separation of multi-component systems. In these apparatuses, a particle packed column is generally used, but the packing process is very difficult and it is difficult to produce the column with good reproducibility. Moreover, those device structures are complicated.

  As an example of the cross flow type adsorption separation apparatus, continuous cylindrical chromatography (CAC) is given. The CAC has a cylindrical column and continuously supplies a sample from a fixed port, and only the column is rotating. A schematic diagram of the apparatus is shown in FIG.

  In order to show the continuous separation mechanism by CAC, first consider a mobile phase chromatographic separation apparatus in which a plurality of chromatographic columns as shown in FIG. 46 are arranged in a circle. FIG. 46 is a diagram showing a state of separation in the mobile phase chromatographic separation apparatus, and changes in time from the upper left diagram to the lower right diagram. FIG. 46 shows the change with time of the position of each sample component when the eluent was supplied uniformly from the upper end of the column and the sample was supplied batchwise from the fixed port. Components having a weak affinity with the adsorbent (shown in red in FIG. 46) move downward in the column faster, and components having a strong affinity (shown in blue in FIG. 46) move slower. When the column is rotated in the direction of the arrow in FIG. 46, the position at which each component flows out at the lower end of the column differs when observed from the fixed axis.

  The cylindrical column is the ultimate form of this mobile phase chromatographic separation device. FIG. 47 shows the state of each component when the eluent is uniformly supplied from the upper end of the cylindrical column and the sample is continuously supplied from the fixed port. FIG. 47 is a diagram showing a state of separation in the CAC device, and changes in time from the upper left diagram to the lower right diagram. Similar to the mobile phase type chromatographic separation apparatus shown above, each component draws a different orbit due to the difference in adsorptivity and descends in the column. Each component can be continuously separated by the difference in the position of the outlet at the lower end of the column.

  Although a two-component separation is shown here, CAC is essentially effective for separating three or more components. For continuous separation of two-component systems, a pseudo mobile phase type chromatographic separation apparatus is excellent.

  Moreover, there exist the following as well-known literature. That is, Non-Patent Documents 1, 3, 4, and 5 are academic papers written about the shear drive type chromatographic separation apparatus.

  An example of a microchemical device in which a fluid is driven by a shearing force. The fluid in the micro-sized channel is not driven by the pressure and electric force used in the past, and shear flow is generated between the adsorbing plates using shearing force. Reported to perform liquid phase chromatographic separation. The basic structure of the device is two rectangular flat plates with adsorbent even on one side, and shear flow (quotes) is generated by shifting one flat plate at a constant speed. The novelty of these techniques is that the flow is not generated by pressure loss but is created by shear forces. However, the apparatus described here has a structure in which continuous separation is impossible.

Non-Patent Document 2 is continuous cylindrical chromatography. Chemical apparatuses capable of continuous separation or continuous reaction separation have been proposed for a long time, and are also published in such textbooks. However, these devices generate a flow in the gap between the adsorbent fillers by pressure and perform separation, and those that generate a flow by shearing force are conventional continuous separation devices. There is nothing.
Gino V. Baron et al, "On the possibility of share-driving chromatography: a theoretic performance analysis", Journal Chromatogr. A, (1999), 855, 57-70. “Continuous Annular Chromatography”, Advances in Biochemical Engineering Biotechnology 76 Modern Advances in Chromatography, Springer Gino V. Baron et al., “The Possibilities of Generating High-Seed Shear-Driving Flows and Therial Application in Liquid Chromatography”, Anal. Chem. (2000), 72, 2160-2165. Gino V. Baron, et al., "Experimental demonstration of the positive to perform shear-driven chromatographic separations in micro-channels", Journal Chromato. A, (2001), 924, 111-122 Desmet G. et al. , Et al., "Experimental Van Dementer of the share-driven liquid chromatographic separations in disposable microchannels," Journal Chromatogr. A, (2003), 987, 39-48.

  In the shear drive type chromatographic separation apparatus of Non-Patent Documents 1, 3, 4, and 5, separation can be performed batchwise, but separation cannot be performed continuously. In the continuous cylindrical chromatography of Non-Patent Document 2, a particle packed column is used, the particle packing process is very difficult, and it is difficult to produce a column with good reproducibility. Moreover, the device structure is complicated. Furthermore, it is a mechanism that generates a flow by pressure. Therefore, to increase the separation efficiency, the packing rate of the adsorbent filler must be increased, and the pressure increases accordingly. Therefore, the separation efficiency is limited by the limitation of the pressure pump and the pressure resistance on the apparatus.

  In the present invention, the concept of Non-Patent Documents 1, 3, 4, and 5 in which the eluent is driven by shearing force and the conventional concept of continuous separation and continuous reaction separation are combined to achieve shear-driven continuous chromatographic separation. To do. In other words, an apparatus has been developed that continuously performs chromatographic separation using the cross flow concept of a conventional continuous separation apparatus while flowing an eluent between adsorbents by a shear drive. The problems that have been solved are that the known techniques of Non-Patent Documents 1, 3, 4, and 5 can be continuous, and for Non-Patent Document 2, the separation of the continuous device by pressure is stopped, This is the point of avoiding the limitation of separation ability due to the limitation of the pressure resistance of the apparatus.

  That is, an object of the present invention is to obtain a scientific apparatus and a separation method such as a shear drive type chromatographic separation device capable of continuous separation by extending SDC technology and incorporating CAC continuation technology.

  A new device was developed, taking into account the fact that a thin-layer column was used to drive the eluent by shearing force and that continuous separation was performed depending on the position of the extraction port.

  As 1 of this invention, it has the active substance of the board B about the board A which has a several parallel flat plate and has the at least 1 sample insertion port of the said parallel flat plate, and the board B which has an active substance on the surface. The surface is arranged facing the plate A, has a function of rotating at least one of the plates A or B, and has a product outlet on the outer periphery of the plate A or B Is a scientific device characterized by

  As a second aspect of the present invention, there is provided a separation method characterized in that a sample is present on opposite plates, and a product generated from the sample is separated by a shear stress generated by rotating one or both of the plates. .

  The sample may be composed of a single component or a plurality of components. In the case of a plurality of components, there are simply a case where a plurality of components are present, a case where a solute and a solvent are used.

  When the product to be separated is a plurality of components, there are a case where the product is simply separated into each component, a case where a substance in a sample reacts, and a newly produced substance is separated.

  When the sample is a single substance, it may be separated into a product that can be reacted in the apparatus and other substances.

  The active substance is not particularly limited as long as it acts on the sample. For example, the active substance has affinity for the substance in the sample used for column chromatography, or has an adsorption action, or a catalyst that acts on the sample. .

  The form of the apparatus according to the present invention is sufficient if at least the plates A and B facing each other are configured as a unit, and a plurality of such units may be stacked. Moreover, you may be comprised with not only two plates but multiple plates. In the case of being composed of a plurality of plates, for example, when it is composed of three plates, the middle plate can have sample inlets from both sides, and the plates B can be arranged on both sides of the plate. Furthermore, one plate is provided with a sample inlet on one side and a plate having an active substance on the other side, and a plurality of plates so that the side having the sample inlet and the side having the active substance face each other. It can also be combined.

  Specifically, the microchemical apparatus of the present invention uses two circular parallel plates having a thin layer adsorbent and a reaction catalyst, attaches the adsorbent to the upper plate, and rotates the plate in the circumferential direction. Generate shear flow of eluent. At the same time, by flowing the eluent from the center of the circular flat plate toward the outside, a Poiseuille flow of the eluent is generated from the center to the outer peripheral direction, and a cross flow is formed in a micro space sandwiched between two circular parallel flat plates. A continuous separation or a continuous reaction separation can be performed by flowing a liquid to be separated therein. By changing the operating conditions such as the flow rate and the rotational speed and the apparatus shape, the separation efficiency and the outlet for taking out the separated substance can be changed.

This device is characterized by having the following configuration. That is,
(1) It is a continuous separation technology by shear force drive that does not use pressure as a driving force. (2) It is a technology that separates in a micro space created by parallel plates. (3) This technology generates shear flow by rotation. (4) Adsorbent / catalyst is attached to a parallel plate and separation is performed using the difference due to the difference in diffusion resulting from the difference in molecular affinity, or it can be performed simultaneously while reacting. (5) Shear by rotation By applying the flow for a limited time, it can be used not only for the continuous type but also for the batch type. (6) By being used for the batch type, it can also be used as a rotational shear force driven chromatographic analyzer. It is.

  As described above, the scientific apparatus and the separation method according to the present invention can use a thin-layer column, and can be continuously separated in consideration of the point that the eluent is driven by shearing force and the point of continuous separation depending on the position of the extraction port. It is possible to obtain a microchemical apparatus such as a shear drive type chromatographic separation device.

Specifically, the following effects can be obtained.
(1) Separation can be performed without being limited by the pumping ability of the pump and the pressure of the apparatus.
(2) In the conventional chromatographic separation method, it was necessary to fill the adsorbent so as not to cause channeling of the flow. However, such difficulty is eliminated, and the adsorbent is simply applied and the operability is low. It can greatly improve.
(3) By continuously rotating the rotating circular plate, the chromatographic separation can be performed continuously. Further, by rotating the disk only for a predetermined time, a technique that can be used for analysis can be obtained.
(4) In addition to coating the adsorbent with a thin film on the circular plate, the reaction / separation process can be carried out simultaneously by applying the adsorbent concentrically on the outside of the center of the disk.

[1. The purpose of this research〕
An object of the present invention is to develop a shear-driven chromatographic separation device (scientific apparatus) capable of continuous separation by extending SDC technology and incorporating CAC continuation technology.

[2. (New chromatographic separation device)
A photograph of the developed chromatographic separation device is shown in FIG. 1, and a schematic diagram of the whole is shown in FIG. 2, FIG. 3, and FIG.

  The new device consists of two disc-shaped flat plates, the lower flat plate is fixed, and only the upper flat plate rotates. Two types of diameters of 8 cm and 12 cm for the upper plate and 8 cm and 16 cm for the lower plate were prepared. The photograph in FIG. 1 is a combination of an upper flat plate with a diameter of 12 cm and a lower flat plate with a diameter of 16 cm. The eluent supply channel and the sample supply channel are formed in the lower flat plate, the channel diameter of the vertical portion is 2 mm, and they are arranged with an interval of 2 cm. The thicknesses of the upper and lower flat plates are arbitrary, but in this device, the upper flat plate thickness is 1 cm and the lower flat plate thickness is 4 cm.

  The upper flat plate is connected to a rotating motor of a Contraves rheometer (Rheomat 120). The rheometer has the feature that the rotational speed can be precisely controlled. A syringe pump was used for liquid feeding, and the syringe and the apparatus were connected by a silicon tube.

  A black square dot scattered in the photograph of FIG. 1 is a double-sided tape (which fixes a sample stage and a sample of a scanning electron microscope SEM). Both the upper and lower flat plates are made of transparent PVC, and the tape is used to bond glass plates to the respective surfaces.

  If it demonstrates further, the example of the microchemical apparatus which consists of two disk type flat plates will be shown in FIG. 2 and FIG. The lower plate is fixed and only the upper plate rotates. A solution supply port is formed in the lower plate. The two disk-type flat plates are arranged in parallel with a micro-size interval. An adsorbent and a reaction catalyst are coated on the upper plate.

  In order to describe the structure of the new device in detail, a schematic diagram (adsorbent surface view) of the upper plate shown from the upper side shown in the upper side of FIG.

  The two disk-type flat plates are arranged in parallel with an interval of 130 μm. This 130 μm corresponds to the thickness of the spacer, and a Teflon (registered trademark) film was used as the spacer. A Teflon (registered trademark) film is cut into a donut shape and disposed between an upper flat plate and a lower flat plate.

  An adsorbent is applied in a thin layer having a thickness of 80 μm on the upper plate. A TLC (Thin-layered Chromatography) plate was used for the adsorbent thin film. Various products are sold for TLC plates, and M Nagel has a wide variety. In this device, a Whatman silica gel TLC plate (K6 60 mm) was used. The adsorbent film thickness at the time of purchase is 250 μm. The periphery of the adsorbent film was masked with a Teflon (registered trademark) adhesive tape having a thickness of 80 μm, and the adsorbent film having a thickness of 80 μm was produced by cutting to the tape thickness. Therefore, the thickness of the microchannel formed between the adsorbent surface and the lower flat plate surface is about 50 μm. The adsorbent film thickness after cutting was measured using an electronic micrometer.

  The eluent is continuously supplied from the center of the lower plate to the micro space between the two plates from a position 2 cm away from the center of the lower plate to the outer periphery. The sample moves from the center to the periphery along the spiral eluent flow. Each component draws a different spiral trajectory due to the difference in adsorptivity and is continuously separated due to the difference in the position of the take-out port on the outer periphery of the apparatus. By changing the flow rate of the eluent and the rotational speed of the upper plate, the spiral trajectory of each component can be controlled, and continuous separation is possible.

  The device does not create a solution outlet port. The solution supplied between the two flat plates oozes out from the gap between the spacer and the flat plate.

  FIG. 6 shows the state of the sample from the start of sample supply on the adsorbent surface. Each component draws a different spiral trajectory and shows how it reaches the outer periphery of the device.

  Further, the lower flat plate is fixed and only the upper flat plate rotates. The two disk-type flat plates are arranged in parallel with an interval of, for example, 50 μm. An adsorbent is coated on the upper plate in a thin layer of, for example, 80 μm, and the eluent is continuously from the center of the lower plate and the sample is continuously moved into the micro space between the two plates from a position off the center. To supply.

  The sample moves from the center to the periphery along the spiral eluent flow. Each component draws a different spiral trajectory due to the difference in adsorptivity and is continuously separated due to the difference in the position of the take-out port on the outer periphery of the apparatus.

  By changing the flow rate of the eluent and the rotational speed of the upper plate, the spiral trajectory of each component can be controlled, and continuous separation is possible.

[3.1 Experiment contents]
[3.1.1 Flow in new device micro space]
The coordinates of the developed device are shown in FIG. Within the microchannel, a Couette flow is generated in the θ direction (rotation direction), and a Poiseuille flow is generated in the r direction (radial direction). The Couette flow is derived from a shear force drive and is a linear velocity profile, and the Poiseuille flow is derived from a pressure drive and is a parabolic velocity profile.

[3.1.2 Contents of experiment]
In order to evaluate the chromatographic separation performance of the developed device, batch separation experiments and continuous separation experiments were conducted. In the batch separation experiment, separation experiments were performed in the flow fields of Couette and Poiseuille, and the height of the theoretical plate (HETP), which is a performance evaluation function of chromatography, was calculated. The smaller the theoretical plate height, the better the chromatographic performance. We also conducted continuous separation experiments, which are a combined Couette-Poiseuille flow field.

[3.2 Separation experiment]
[3.2.1 Couette flow field]
[3.2.1.1 Experimental equipment]
For batch separation experiments in the Couette flow field, a new device with a diameter of 8 cm was used for both the upper and lower plates. A groove having a width of 1 mm is formed linearly from the sample inlet position (position 2 cm from the center) to the outer periphery in the radial direction in the adsorbent film so that the sample can be arranged linearly at the start of the experiment.

[3.2.1.2 Sample]
As described above, a TLC silica plate (Whatman K6 60Å) was used for the adsorbent thin film.

  A mixed solution of 1-Propanol (Wako 162-04816) and Formic Acid (Wako 066-00466) was used as an eluent. The mixing ratio is Formula Acid / 1-Propanol = 1/2 vol.

  A blue and red dye mixed solution was used as a sample to be separated. Methylene Blue (Merck) was used as the blue dye, and Rhodamine B (Wako 183-00122) was used as the red dye. The concentration of the dye mixture solution was 1 mM, the molar ratio of Methylene Blue to Rhodamine B was 1: 1, and an eluent was used as the solvent.

  A simple TLC separation experiment was also conducted with reference to the literature for selection of the dye species.

[3.2.1.3 Experimental procedure and experimental conditions]
(1) Operate the eluent side syringe pump to fill the microchannel with the eluent. Thereafter, the supply of the eluent is stopped.

  (2) The sample side syringe pump is operated, and the sample (dye) is linearly arranged in the channel. At this time, the supply flow rate of the sample is several ml / h.

  (3) Operate the rheometer motor and rotate the upper plate. The eluent is driven by the shearing force, and the sample is separated into each component.

  (4) After a certain time, slowly release the upper and lower flat plates. The eluent on the surface of the adsorbent is vaporized as soon as possible, and after drying to some extent, the surface of the adsorbent is stored in an image by a scanner.

  The rotating plate (upper plate) is operated at 0.01, 0,015, 0.02, 0.025, 0.03, 0.035, and 0.04 rpm, and the separation experiment is performed twice at each rotational speed. It was. The state of the dye on the surface of the adsorbent before and after separation is shown in FIGS. 8 (a) and 8 (b).

  FIG. 8A shows the state of the dye on the adsorbent surface before separation and FIG. 8B shows the state after separation.

[3.2.2 Poiseuille flow field]
[3.2.2.1 Experimental equipment]
A flat plate device was used for batch separation experiments in the Poiseuille flow field. The configuration of the flat plate device is shown in FIG. 9, and a schematic diagram is shown in FIG. The flat plate device consisted of two glass plates, and an adsorbent was applied to the surface of one glass plate. That is, one of the glass plates (the one on which the adsorbent is applied) is the TLC plate itself. The adsorbent film thickness is 80 μm as in the new device. A spacer (a Teflon (registered trademark) sheet having a thickness of 130 μm) is sandwiched between two glass plates to produce a microchannel. Therefore, the thickness of the microchannel is about 50 μm, and the column sizes such as the channel thickness and the adsorbent film thickness are all the same as the new device. Epoxy resin was used for joining the two glass plates.

  In order to arrange the sample in a straight line in the column, a sample inlet was formed on the side surface of the flat plate device, and a groove having a width of about 1 mm was formed in the adsorbent film perpendicular to the eluent flow.

[3.2.2.2 Sample]
The sample is similar to the batch separation experiment in the Couette flow field.

  As described above, a TLC silica plate (Whatman K6 60Å) was used for the adsorbent thin film.

  A mixed solution of 1-Propanol (Wako 162-04816) and Formic Acid (Wako 066-00466) was used as an eluent. The mixing ratio is Formula Acid / 1-Propanol = 1/2 vol.

  A blue and red dye mixed solution was used as a sample to be separated. Methylene Blue (Merck) was used as the blue dye, and Rhodamine B (Wako 183-00122) was used as the red dye. The concentration of the dye mixture solution was 1 mM, the molar ratio of Methylene Blue to Rhodamine B was 1: 1, and an eluent was used as the solvent.

[3.2.2.3 Experimental procedure and experimental conditions]
(1) Operate the eluent side syringe pump to fill the microchannel with the eluent. Thereafter, the supply of the eluent is stopped.

  (2) The sample side syringe pump is operated, and the sample (dye) is linearly arranged in the channel. At this time, the supply flow rate of the sample is several ml / h.

  (3) The eluent side syringe pump is operated again. The eluent is driven by pressure, and the sample is separated into each component.

  (4) After a certain period of time, the eluent and the silicon tube at the sample inlet are removed, and the eluent in the column is aspirated instantaneously using a syringe. After the adsorbent has dried to some extent, the entire apparatus is put into an image by a scanner.

  Since the device is made of a transparent glass plate, the state of the dye on the adsorbent film can be observed by putting the entire device in an image. The eluent flow rate was varied by changing the eluent flow rate. In the flat plate type device, the eluent easily flows on the side surface of the adsorbent film (between the adsorbent and the Teflon (registered trademark) sheet spacer), and it is difficult to calculate the flow rate from the flow rate input to the syringe pump. Accordingly, the eluent flow rate was calculated from the moving distance of the color intensity distribution peak position of the dye and the capacity coefficient of each component as described later.

  The state of the dye on the adsorbent surface before and after separation is shown in FIG. The state before separation is shown in FIG. 9A, and the state before separation is shown in FIG. The dye (sample) is separated as shown in A and B in the figure.

[3.3 Continuous separation experiment]
[3.3.1 Experimental equipment]
In the continuous separation experiment, a device having an upper plate diameter of 12 cm and a lower plate diameter of 16 cm was used.

[3.3.2 Sample]
The sample is the same as in the batch separation experiment.

  As described above, a TLC silica plate (Whatman K6 60Å) was used for the adsorbent thin film.

  A mixed solution of 1-Propanol (Wako 162-04816) and Formic Acid (Wako 066-00466) was used as an eluent. The mixing ratio is Formula Acid / 1-Propanol = 1/2 vol.

  A blue and red dye mixed solution was used as a sample to be separated. Methylene Blue (Merck) was used as the blue dye, and Rhodamine B (Wako 183-00122) was used as the red dye. The concentration of the dye mixture solution was 1 mM, the molar ratio of Methylene Blue to Rhodamine B was 1: 1, and an eluent was used as the solvent.

[3.3.3 Experimental procedure and experimental conditions]
(1) The rheometer motor is operated and the eluent side syringe pump is operated while rotating the upper flat plate to fill the microchannel with the eluent. The upper plate rotation speed was set to 0.01 rpm. At this time, it is necessary to remove the microbubbles in the channel by relatively increasing the flow rate.

  (2) The eluent side syringe pump is set to a flow rate of 5 ml / h, then the sample side syringe pump is operated, and the eluent and sample (dye) are continuously supplied into the channel. The sample flow rate was set to 0.1 ml / h.

  (3) When the locus of the dye in the column becomes steady (after about 1 hour from the start of sample supply), the rotation of the upper plate, the eluent, and the sample supply are stopped simultaneously.

  (4) After (3) above, the upper flat plate is instantly removed, and the eluent of the adsorbent film is vaporized. After the adsorbent has dried to some extent, the surface of the adsorbent is put into an image by a scanner.

  The process (4) should be performed as quickly as possible. This is because if the eluent remains in the adsorbent film, the sample diffuses and blurs. The eluent flow rate was set at 5 ml / h, but the net flow rate was 0.9 ml / h. Since the eluent is supplied into the micro space, the pressure loss is large and the eluent cannot be supplied at the set value of the syringe pump. While supplying the eluent at a syringe pump set value of 5 ml / h, the net flow rate was calculated from the sample moving distance when the sample was supplied in pulses.

[3.4 Analysis]
[3.4.1 Image analysis method]
After the batch separation experiment and the continuous separation experiment, the surface of the adsorbent film is put into an image by a scanner, and the image is analyzed. Specifically, the color intensity of each component (blue and red) of the dye is plotted. In batch separation experiments in the Couette flow field, the color intensity distribution on the circumference with a radius of 30 mm, in the batch separation experiment in Poiseuille flow field, the color intensity distribution on a straight line suitable for the eluent flow, and in the continuous separation experiment with a radius of 25 The color intensity distribution on the circumference of 30 mm and 35 mm was obtained.

  As an index of color intensity, the saturation of the Yxy color system was used. FIG. 12 shows the Yxy color system. Saturation increases in the direction of the arrow in the figure.

  The RGB value for each pixel of the adsorbent surface image is read using MATLAB (registered trademark) and converted into a Yxy value. The conversion method is shown below.

  (1) Read RGB data of each pixel from the image.

  (2) As shown in Equation (3.4.1.a), each sRGB value is divided by 255 to obtain a real value from 0 to 1, and converted to linear RGB (1R, 1G, 1B).

  (3) The linear RGB is converted into the tristimulus values CIEXYZ (X, Y, Z) proposed by the International Commission on Illumination (CIE) from the formula (3.4.1.b).

  (4) The x and y values in the Yxy color system are calculated from the equation (3.4.1.c).

  In the same procedure as the batch separation experiment in the Couette flow field, the blue and red dye solutions were not used for the sample, but the blue dye solution and the red dye solution were used for the experiment. After the experiment, the adsorbent surface image was analyzed, x and y were calculated by the procedure described above, and the plotted results are shown in FIG. Y and x in the Yxy color system are taken on the vertical axis and the horizontal axis, respectively. In the figure, points in the range indicated by A are the x and y values when using a blue dye solution, and the range indicated by B in the figure. The dots indicate the x and y values when a red dye solution is used. Plot points indicate the results of experiments performed multiple times on each solution.

  It can be seen from FIG. 13 that the blue and red plot points are arranged in a straight line. Therefore, all the blue and red data are approximated to a straight line, and the result is the blue and red straight lines shown in the figure. This straight line was used as a reference line for calculating the intensity of each color. The x and y values of the blue and red components are all on this straight line, and the distance from the origin (the intersection of the blue and red straight lines) is considered to be proportional to the color intensity. Here, as the distance from the origin is longer, the saturation becomes larger, so the saturation is used as an index of color intensity.

  Next, a method for calculating the color intensity of each component for a portion where blue and red are mixed (a portion where blue and red are mixed and purple) will be described with reference to FIG. When two points having x and y values in the Yxy color system are mixed in “equal amounts”, the resulting mixed color is a color represented by the coordinates of the midpoint of the line segment connecting the two points. Here, “equivalent amount” does not specifically represent the amount of dye or the like, but simply means that these two points are mixed in the same degree (intensity), and in this image analysis method, the mixed color is blue, It was assumed that each point on the red reference line was always mixed at the same degree. The mixed color portion exists below the blue reference line and to the left of the red reference line. When the mixed color portion is subjected to image analysis and the point where x and y in a certain pixel are plotted is point A, point A is the midpoint of point B on the blue reference line and point C on the red reference line. That is, when a mixed color represented by point A is obtained, the blue and red color intensities at point A become the color intensities at points B and C, respectively. Dividing an arbitrary mixed color into blue and red color intensities means that two points on the reference line (one point each from the blue reference line and the red reference line) are mixed points at the midpoint of these two line segments. Is to choose.

[4. Results and discussion〕
[4.1 Color intensity plot]
As an example of a color intensity plot, the results of a batch separation experiment in a Couette flow field are shown. FIG. 15 shows an adsorbent surface image after the separation experiment. The color intensity on the circumference in FIG. 15 is plotted and shown in FIG. FIG. 16 shows that the image analysis method used this time can express the color intensity of each color well.

[4.2 Calculation method of capacity coefficient]
From the batch separation experiment in the Couette flow field, the volume coefficient of each sample component in the system used in this experiment was calculated. The capacity coefficient was calculated from the equation (4.2.a).

k ′ is a capacity coefficient, L ₀ is a moving distance of the eluent as a non-retaining component, and L _eff is a moving distance of the color intensity peak position of each component. The results of batch separation experiments in the Couette flow field are taken as an example, and L ₀ and L _eff are shown. FIG. 17 shows an adsorbent surface image after the separation experiment, in which L ₀ and L _eff are shown together. Since the adsorbent rotates clockwise, the eluent moves relatively counterclockwise. In addition, since the operation conditions of the batch separation experiment given as an example are a rotation speed of 0.03 rpm and an operation time of 10 min, the upper flat plate (rotary plate) has rotated by 108 ° from the start of the experiment, and the eluent speed is the rotational plate speed. And the eluent has moved 54 °. In consideration of these points, the initial sample position, eluent movement direction, and L ₀ are shown in FIG. The color intensity on the circumference in FIG. 17 is plotted and shown in FIG. 18, and the position of L _eff is also shown.

[4.3 Theoretical plate height calculation method]
The theoretical plate height was calculated under each operation condition from the results of batch separation experiments. When the theoretical plate height is obtained experimentally, the equation (4.3.a) is used.

HETPexp is the theoretical plate height obtained experimentally, σ _in and σ _out are the color intensity distribution dispersion values of each component before and after the separation experiment, and L _eff is the moving distance of the color intensity peak position of each component. . When the color intensity distribution conforms to a Gaussian function, the color intensity distribution dispersion value and the color intensity peak width are in the relationship of Expression (4.3.b).

  W in a formula shows a peak width. Further, the peak width is obtained from the peak half-value width W1 / 2 from the equation (4.3.c).

  Before the separation experiment, that is, when the sample is arranged linearly in the column, the color intensity distribution is rectangular. When the color intensity distribution is rectangular, the distribution variance value is zero. Actually, although the color intensity before the separation experiment has a distribution close to a Gaussian function, it is considered to be zero here, and the equations (4.3.a) (4.3.b) (4.3.c) Are obtained, the equation (4.3.d) is obtained.

  Using equation (4.3.d), the theoretical plate height can be calculated from the half-value width of the color intensity distribution peak after the separation experiment and the moving distance of the color intensity peak position of each component.

[4.4 Derivation of HETP theoretical formula]
The HETP theoretical formula in the column format of the developed device (a flat column with an adsorbent thin film arranged on one flat plate) was obtained. As described above, a Couette flow is generated in the θ direction and a Poiseuille flow is generated in the r direction in the device microspace. Therefore, the HETP theoretical formula in each flow field in a flat column is required. The theoretical formula in the Couette flow field is given by the formula (4.4.a) from the reference.

  On the other hand, the theoretical formula in the Poiseuille flow field is derived as shown in the following formula (4.4.b) with reference to the literature.

  The derivation procedure is as follows.

[Derivation of HETP theoretical formula in flat column Poiseuille flow field]
The HETP theoretical formula in the Poiseuille flow field was derived according to the procedure of the reference. In order to obtain the necessary HETP theoretical formula, the assumed column shape and velocity profile are shown in FIG.

  Considering a virtual velocity profile in which the Poiseuille flow is vertically symmetric as shown in FIG. 19, the HETP theoretical formula can be calculated for the device developed (corresponding to the upper or lower half of FIG. 19) by following the procedure of the reference. . Assuming that the average flow velocity is (3/2) v, this virtual velocity profile is expressed by the following equation.

  As the boundary condition, the HETP theoretical formula (formula (4.4.b)) in the Poiseuille flow field can be derived by solving the partial differential equation using (1), (4), and (5).

  Further, since the HETP theoretical formula in the Couette flow field is described in the publicly known literature, the explanation is omitted.

Equation (4.4.a) k 'is the capacity factor in (4.4.b), u _m the eluent average flow velocity, D _m, D _s respectively mobile phase, stationary phase molecular diffusion coefficient, d, d _f represents the mobile phase and stationary phase thickness. The first term on the right side of each HETP theoretical formula is the contribution term due to diffusion in the vertical direction (eluent flow direction) in the mobile phase, the second term on the right side is the contribution term due to the delay of mass transfer in the mobile phase, and the third term on the right side. Indicates the contribution term due to the delay of mass transfer in the stationary phase. Since the velocity profile in the mobile phase is different in each flow field, a difference is seen in the second term on the right side in the equations (4.4.a) and (4.4.b).

[4.5 separation experiments]
[4.5.1 Couette flow field]
[4.5.1.1 Capacity coefficient]
The capacity coefficients of blue and red in the system used in this experiment were calculated by the method described in 4.2.

The horizontal axis represents the moving distance L ₀ of the eluent as a non-retained component, the vertical axis represents the moving distance L _eff of the color intensity distribution peak position of each component, FIG. 21 shows the blue component, and FIG. 22 shows the red component. The calculation method of a capacity coefficient is shown. The white circles in the figure are the experimental values, and the solid line is the result of approximating the experimental values with a straight line passing through the origin. It can be seen from the figure that each experimental value is almost on a straight line. Since equation (4.5.1.1.a) is obtained by transforming equation (4.2.a), the capacity coefficient of each component is calculated from the slope of the approximated straight line.

  The obtained capacity coefficients are summarized in FIG.

[4.5.1.2 Theoretical plate height]
The theoretical plate height is calculated by the method described in 4.3 and is shown in FIG. The horizontal axis represents the average eluent flow rate, the vertical axis represents the theoretical plate height, the blue circle represents the blue dye, and the red circle represents the red dye. As described in 3.2.1.3, the rotating plate (upper plate) is operated at 0.01, 0,015, 0.02, 0.025, 0.03, 0.035, 0.04 rpm, Separation experiments were performed twice at each rotation speed. The theoretical plate height is calculated by analyzing the color intensity on the circumference having a radius of 30 mm on the surface of the adsorbent. Therefore, the average eluent flow velocity is the flow velocity on the circumference.

  In another example, the theoretical plate height obtained from the experiment is shown in FIG. The solid line in FIG. 24 is a value calculated from the theoretical formula giving the theoretical plate height in the Couette flow in the flat column. The theoretical values and the experimental values are in good agreement, and even when used in this device, chromatographic column performance with a theoretical plate height of several hundred μm could be expressed.

[4.5.2 Poiseuille flow field]
[4.5.2.1 Volume coefficient and average eluent flow rate]
As described in 3.2.2.3, in the batch separation experiment in the Poiseuille flow field, a flat plate device is used, and it is difficult to calculate the average eluent flow rate from the syringe pump set value. By performing image analysis, the moving distance L _{eff of the} peak position of the color intensity distribution is known, and the capacity coefficient is known (see 4.5.1.1), and the moving distance of the eluent from equation (4.2.a). L ₀ can be calculated. The average eluent flow rate was calculated from this and the experiment time (elapsed time from before separation to after separation).

[4.5.2.2 Theoretical plate height]
The theoretical plate height is calculated by the method described in 4.3 and is shown in FIG. The horizontal axis represents the average eluent flow velocity, the vertical axis represents the theoretical plate height, the filled triangles indicate the results for the blue dye, and the unfilled triangles indicate the results for the red dye. The method for calculating the average eluent flow rate is described in 4.5.2.1.

[4.5.3 Comparison of experimental and theoretical values for theoretical plate height]
The results (theoretical plate height) of the batch separation experiment are shown in FIGS. 26 and 27 for the blue dye and the red dye, respectively. The horizontal axis represents the average eluent flow velocity, the vertical axis represents the theoretical plate height, and the circles in the figure are the results of batch separation experiments in the Couette flow field, and the triangles in the Poiseuille flow field. The solid and broken lines are the theoretical values for the Couette flow field and the Poiseuille flow field, respectively. The Couette flow field is calculated from the equation (4.4.a), and the Poiseuille flow field is calculated from the equation (4.4.b) ( 4.4). Here the mobile phase molecular diffusion coefficients ^{_{D m = 1.0E-9 m 2}} / s , the fixed phase molecular diffusion coefficient and ^{_{D s = 1.0E-10 m 2}} / s. Appropriate diffusion coefficient values were selected with reference to the literature.

  The experimental results show that the theoretical plate height in the Couette flow field tends to be larger than the theoretical plate height in the Poiseuille flow field. This is thought to be due to the difference in velocity profiles at each flow field. At the same average velocity, the Couette flow has a larger velocity distribution than the Poiseuille flow, and the sample distribution in the column tends to spread, and as a result, the theoretical plate height tends to increase. It can be seen that the chromatographic performance of this device is about 500 μm in theoretical plate height. In particular, the theoretical values agree well with the experimental values especially in the low flow rate region, and the chromatographic performance of this device can be estimated using the theoretical formulas (formulas (4.4.a) and (4.4.b)). Recognize.

[4.5.4 Dependence of theoretical plate height on channel thickness and adsorbent film thickness]
FIG. 28 shows how the theoretical plate height changes when the mobile phase (microchannel) thickness and the stationary phase (adsorbent film) thickness are changed. In each graph, the vertical axis represents the theoretical plate height, the horizontal axis represents the eluent average flow velocity, and the theoretical plate height is calculated using theoretical formulas (formulas (4.4.a) and (4.4.b)). Calculated. The solid line shows the theoretical value in the Couette flow field, and the broken line shows the theoretical value in the Poiseuille flow field. The capacity coefficient k ′ is 1.42, the mobile phase molecular diffusion coefficient D _m and the stationary phase molecular diffusion coefficient D _s are 1E-9 and 1E-10 m ² / s, respectively. It showed the condition of the agent layer thickness d _f.

  As can be seen from each graph, the value in the Poiseuille flow field is smaller than that in the Couette flow field, indicating that the chromatographic performance in the Poiseuille flow field is better.

  It can be seen that the chromatographic performance improves as the adsorbent thickness decreases. This is clear from the theoretical formula. Even in a high flow rate region, the theoretical plate height does not increase so much, and it can be seen that the eluent can flow at a high speed without excessively broad concentration distribution. On the other hand, if the adsorbent film thickness is too small, there is also a drawback that the capacity that the adsorbent can hold becomes small.

  As the microchannel thickness is decreased, the chromatographic performance is improved, as is the adsorbent film thickness. On the other hand, for example, when the channel thickness is 100 μm, the theoretical plate height in the Couette flow field is larger than that in the Poiseuille flow field, and the difference between them becomes smaller as the channel thickness decreases, and the theoretical plate height in each flow field is the same. It will be something. From this point, it can be seen that in this device, the channel thickness is desirably about 50 micrometers or less in order to avoid excessively broad concentration distribution due to shear flow.

  A TLC plate with the same film thickness as the adsorbent film of the developed device was immersed in the sample (dye mixture solution) for a long time, and after drying, the surface of the adsorbent on the TLC plate was subjected to image analysis. The color intensity obtained thereby was used as the color intensity of each component at the sample concentration. Assuming that the color intensity and density are in a proportional relationship, a dimensionless density was calculated from the color intensity.

FIG. 29 shows an adsorbent surface image after the continuous separation experiment, and FIG. 30 shows a dimensionless concentration distribution calculated from the color intensity distribution on an arc having radius r of 25, 35, and 45 mm in FIG. In the figure, A is a blue dye and B is a red dye. FIG. 30 is a three-dimensional plot of the dimensionless concentration against the radius r and the angle θ from the sample inlet (r and θ are described in FIG. 29). Further, the degree of separation was calculated for the distribution on each arc, and is shown together in FIG. The degree of separation R _s was calculated from the equation (4.6.a) assuming that each dimensionless concentration distribution follows a Gaussian function.

L _{eff, blue} and L _{eff, red} are the movement distances of the blue and red color intensity distribution peak positions, respectively, and W _blue and W _red are the blue and red color intensity distribution peak widths, respectively.

  It can be seen from FIG. 30 that the degree of separation increases and the separation is achieved as the radius r increases toward the outer periphery of the upper flat plate. Although each component is not completely separated, it is considered that continuous separation is possible due to the difference in the position of the take-out port on the outer periphery of the apparatus.

[4.6.2 Estimation of sample trajectory]
In 4.6.1, it was found that continuous separation was possible depending on the position of the outlet on the outer periphery of the apparatus. On the other hand, the sample trajectory must be estimated to determine the operating conditions of the developed device. Obtaining the sample trajectory means calculating the trajectory of the concentration distribution peak position and the concentration distribution width. That is, the concentration distribution widths may be added so as to have a width in the normal direction of the eluent movement direction at each peak position. Here, the eluent movement direction is the θ direction when a Couette flow is considered, and the r direction when a Poiseuille flow is considered. The broadening of the peak due to Couette flow, that is, the concentration distribution width and the concentration distribution width due to Poiseuille flow are calculated separately and compared to each other to express a broader sample trajectory in the combined Couette and Poiseuille flow field. Concentration distribution width.

Since a Couette flow is generated in the θ direction in the microchannel of the developed device, the average eluent flow velocity in the θ direction is half of the rotation speed of the rotating plate, and the equation (4) using the holding volume V _m (1 + k ′) is used. The orbit of the concentration distribution peak position was obtained from .6.2.a).

In the equation, θ is the angle from the sample inlet, ω is the rotational speed of the rotating plate, FT is the total flow rate of the eluent and the sample flow rate, V _m is the mobile phase volume, and k ′ is the capacity coefficient. Since V _m is obtained from the radius r and the microchannel thickness d from the column geometry, the angle θ and the radius r from the sample inlet with respect to the concentration distribution peak position are obtained from the equation (4.6.2.b). .

If the sample entrance position is r ₀ , the following can be written.

On the other hand, the density distribution width W _out is obtained from the equation (4.6.2.c). This is the same as the equation described in 4.3.

  The value calculated from the theoretical formula (formulas (4.4.a), (4.4.b)) was used for HETP. As the capacity coefficient, the value shown in Table 1 (4.5.1.1) was used. The molecular diffusion coefficient was obtained by fitting the theoretical plate height obtained from the batch separation experiment to the theoretical formula using the fitting parameter as the molecular diffusion coefficient. The values are summarized in FIG. 31 and used to calculate the concentration distribution width.

The theoretical formula HETP is a function of eluent average flow velocity u _m. In this device, when the eluent goes from the center to the outer periphery, u _m is not constant and is a function of the radius r. In view of this, a slight change in the equation (4.6.2.c) was considered and integrated to calculate W _out at each L _eff . The calculation of the integral formula is as follows.

[Calculation method of concentration distribution width from HETP theoretical formula]
Here, only the peak spread due to the Poiseuille flow is considered, and a method for calculating the concentration distribution width in the Poiseuille flow field is described. Within the new device microspace, the eluent flow rate is a function of radius r. Therefore, when calculating the concentration distribution width, it is necessary to consider and integrate the slight change in the equation (4.6.2.c).

  Equation (4.6.2.c) can be modified as follows.

Consider slight changes in HETP (hereinafter referred to as H), W _out (hereinafter referred to as W), u _m (hereinafter referred to as u), and t. The squared term is expanded by Taylor, and the following equation is obtained by assuming that the square of a minute amount is zero.

  If (small amount) → 0, the following integration formula is obtained.

  Since the Poiseuille flow field is taken into account, the following equation is obtained from the mass conservation of the eluent in the mobile phase.

r ₀ represents the sample inlet radius, and Q represents the total flow rate. The HETP theoretical formula can be regarded as a function of only the mobile phase average flow velocity u, and the following formula is obtained by simplifying using the constant E.

  Substituting the above fourth and fifth equations into the third equation, setting the integration range from the sample inlet position to an arbitrary position, and integrating, the following material conservation equation is obtained.

Win _{in the} above equation represents the concentration distribution width at the sample inlet. From the above equation, the concentration distribution width W when the concentration distribution peak position is on the radius r can be calculated.

  When considering the broadening of the peak due to Couette flow, that is, the concentration distribution width in the Couette flow field, it can be obtained by the same procedure as described above if the substance conservation equation and the constant E are changed.

  In FIG. 32, the sample trajectory calculated from the equations (4.6.2.b) and (4.6.2.c) is shown together with the adsorbent surface photograph after the continuous separation experiment. In the figure, the range of dotted line A-dotted line A 'indicates the locus of the blue component, and the range of dotted line B-dotted line B' indicates the locus of the red component. The calculated sample trajectory expresses the experimental result well, and it can be seen that the sample trajectory can be roughly estimated by the method described here.

[4.6.3 Estimation of dimensionless concentration distribution]
When the peak broadening due to the Couette flow and the peak broadening due to the Poiseuille flow are considered separately, the Couette flow produces a concentration distribution in the θ direction, and the Poiseuille flow produces a concentration distribution in the r direction, and the concentration distribution can be regarded as following a Gaussian function. Therefore, the concentration distribution width in the θ direction due to the Couette flow and the concentration distribution width in the r direction due to the Poiseuille flow can be calculated by the method shown in 4.6.2. Since the Gaussian function can be uniquely determined by giving the peak width, when the Couette and Poiseuille flows are considered independently, the concentration distributions in the θ direction and the r direction can be calculated, respectively. On an arbitrary circumference, the concentration distribution calculated only considering the peak spread due to the Couette flow and the concentration distribution only considering the peak spread due to the Poiseuille flow are overlapped, and the arithmetic average is taken to obtain the Couette and Poiseuille. Considered the concentration distribution on its circumference in the composite flow field.

  The concentration distribution calculated by the above method is compared with the result of the continuous separation experiment. FIG. 33 shows experimental values and estimated values for the concentration distribution on an arc having a radius of 45 mm on the adsorbent surface image after the continuous separation experiment. The filled circles and unfilled circles are the experimental values of the blue dye and the red dye, respectively, and the solid lines indicated by A and B in the figure are the concentration distribution estimation values for the blue dye and the red dye, respectively. The figure shows that the experimental value is broader than the estimated value. This is considered to be mainly due to contributions to the theoretical plate height outside the column, such as the presence of minute bubbles in the column and bleeding when the upper plate is removed after the experiment.

  In addition, FIG. 34 shows a dimensionless concentration distribution for the result of another example. The eluent flow rate was set to 0.8 ml / h, the sample flow rate was set to 0.1 ml / h, and the upper plate rotation speed was set to 0.01 rpm. The figure shows the result at a position of 45 mm in the radial direction.

  Another example is shown. Using this device, an eluent and a dye mixed solution were continuously supplied, and continuous separation was attempted. 35 and 36 show the results of this separation experiment. FIG. 35 is a diagram showing a sample trajectory. FIG. 36 is a diagram illustrating a result of plotting the color intensity on the line. The image of the adsorbent surface was analyzed. Each dye traced its own trajectory and found that it was separated, and it was found that continuous separation was possible using this device.

[4.6.4 Reproducibility of continuous separation]
Continuous separation experiments were performed under the same conditions, and the adsorbent surface images after the experiments are shown in FIGS. In the figure, the estimated sample trajectory described in 4.6.2 is also shown. In the figure, the range of dotted line A-dotted line A ′ indicates the locus of the blue component, and the range of dotted line B-dotted line B ′ indicates the locus of the red component. Both figures show the reproducibility of continuous separation.

  Both experimental results are in good agreement with the estimated sample trajectories, and the same sample trajectories are drawn. It is considered that continuous separation can be performed with good reproducibility, and it can be said that separation can be continuously performed from a certain outlet.

[4.7 Simple design method for new devices]
[4.7.1 Design equation]
As a summary, we propose a simple proposal method for devices developed. The design equations in the simple design method are formulas (4.4.a), (4.4.b), (4.6.2.b), and (4.6.2.c).

[4.7.2 Simple design method]
The procedure for determining the device design and operating conditions is shown.

(1) Selection of adsorbent and eluent Select an adsorbent and eluent that give an appropriate capacity coefficient k ′ for the component to be separated. Here, the mobile phase molecular diffusion coefficient D _m and the stationary phase molecular diffusion coefficient D _s are determined.

(2) Determination of device size As shown in the results of batch separation experiment (4.5.3), the chromatographic performance was determined using the HETP theoretical formula (formulas (4.4.a) (4.4.b)). Can be predicted. Therefore, the channel thickness d and the adsorbent film thickness _df are reduced and determined to the extent that separation is sufficiently achieved.

(3) Determination of operating conditions As shown in the results of the continuous separation experiment (4.6.2), the orbit of the concentration distribution peak position is expressed by equation (4.6.2.a), and the concentration distribution width is expressed by equation (4. Since the sample trajectory can be estimated obtained from 6.2.b), the eluent flow rate F _E and the rotational speed ω are determined so that each component can be obtained at a desired outlet position. Since the sample flow rate cannot be changed significantly, if the eluent flow rate is determined, the total flow rate (total flow rate of the sample and the eluent) _FT is determined. The apparatus upper plate radius (adsorbent film radius) r _out is arbitrary, but when r _out is changed, the appropriate eluent flow rate F _E and rotation speed ω are changed.

  Device design and operating conditions can be determined by the above procedure.

[4.8 Possibility as multipurpose device]
The characteristics of the developed device include the following two points.
・ Uses a thin-layered adsorbent film instead of a particle-packed type.
-Flat plate device, utilizing the features in micro space to ensure the interface area.

  The particle packing process is very difficult, and it is difficult to produce a column with good reproducibility. In that respect, it is advantageous to use a thin-layered adsorbent film. However, a flat column like this device has lower chromatographic performance than the particle packed type. In order to improve the chromatographic performance in a flat plate type device, it is necessary to make it thinner. The developed device consists of a removable disk-type flat plate, and its device structure is relatively simple compared to CAC.

  Since this device can arrange many kinds of thin films in parallel, it is considered as a mixed separation mode device in which different kinds of adsorbent films are arranged, and a reaction separation device in which catalyst films and adsorbent films are arranged. 39 and 40 show the arrangement of the thin films of the mixed separation mode device and the reaction separation device, respectively.

  Further, since the eluent and sample supply port can be arranged freely, it is conceivable that eluents having different physical properties such as polarity can be supplied into the microchannel from a desired position. FIG. 41 shows the arrangement of the device sample and the eluent supply port. It is considered that there is a possibility of a multi-purpose device using efficient two-phase mass transfer in a micro space rather than a simple chromatographic separation apparatus.

  That is, although the above-mentioned explanation uses this device for the separation of the mixture, it can also be used as a chemical reaction apparatus. That is, as shown in FIG. 40, the catalyst is adsorbed only in a certain diameter range, and the reaction raw material (or one) is allowed to flow from the sample supply port at a predetermined position in the radial direction. When the raw material contacts the catalyst and undergoes a chemical change, the affinity with the adsorbent changes and the speed of advance changes, causing a difference in the speed of advance between the reaction product and the unreacted raw material. Therefore, the reaction product and the unreacted raw material can be separated.

  Another example will be described. FIG. 42 is a sectional view of the device, and FIG. 43 is a view of the upper flat plate as viewed from below. The upper side of FIG. 42 is an example described so far, and the lower side of FIG. 42 is an example in which it is modified. The latter is a substitute for a spacer by finely processing the lower flat plate (glass) to form a protrusion.

  In the example of FIG. 43, porous fibers are spread on the lower flat plate where the dye has oozed out, with a slight gap in the radial direction. When the dye oozes out, it is adsorbed on each fiber. After that, if it extracts from the fiber, the target dye can be obtained.

  In this study, SDC technology was expanded, CAC continuation technology was incorporated, and a new continuous chromatographic separation device using shear force for eluent flow in the micro space was developed. For SDC technology, a thin layer column was used and the eluent was driven by shearing force, and for CAC technology, continuous separation was considered due to the difference in the outlet position.

  Paying attention to the flow of the developed device in the micro space, we conducted batch separation experiments using dye mixed solution in each flow field of Couette and Poiseuille. The chromatographic performance of this device was evaluated by analyzing the color intensity of the dye and calculating the theoretical plate height. In addition, the influence of the mobile phase solution velocity profile on the chromatographic performance in the flat column was compared with the theoretical value calculated from the HETP theoretical formula.

  Using the developed device, continuous separation was performed using a dye mixture solution. By observing how the components to be separated reach the outer periphery (outlet) while drawing different trajectories due to the difference in adsorptivity, the possibility of a continuous separation device was demonstrated. In addition, the sample trajectory was estimated using the HETP theoretical formula, and a simple design method for the developed device was proposed.

  Thus, the microchemical device (scientific device) of the present invention has a plurality of parallel plates, and one of the parallel plates (referred to as plate A) is in a plane parallel to the other parallel plates. At least one sample inlet is provided. This sample insertion port is used to input a sample from the plate A between the plate A and the plate B. Another one of the parallel plates (referred to as plate B) has an active substance on the surface of a plane parallel to the other parallel plates. Both plates A and B are arranged so that the surface of the plate B having the active substance faces the surface of the plate A having the sample inlet. Further, at least one of the plates A and B has a function of rotating without changing the distance between the plates A and B. This rotation is a rotation around an axis that penetrates both flat plates perpendicularly to their parallel flat surfaces. Further, a product outlet may be provided on the outer peripheral portion of the plate A or the plate B. In addition, one plate A having sample inlets on both sides is prepared, and the two plates B are arranged so that each surface having the active substance faces each surface of the plate A having the sample inlets. A configuration in which one plate A is sandwiched by B can also be adopted.

  The microchemical apparatus (scientific apparatus) of the present invention creates a space for moving a sample by a gap between parallel plates, and an active substance such as an adsorbing substance on the surface of at least one of the parallel plates facing the space. The sample can be arranged at a predetermined arrangement position in the space. At this time, the parallel flat plates are relatively rotated without changing the interval. This rotation is a rotation around an axis that penetrates both flat plates perpendicularly to their parallel flat surfaces. Then, with the diffusion rate determined based on the strength of the molecular affinity between the sample and the agent, the sample is rotated from the arrangement position in the space to the parallel plate. It is also possible to make the sample proceed in the direction of rotation of the parallel plate by driving the shear force by the shear flow by generating a shear flow by the rotation of the parallel plate while traveling in the radial direction.

  The present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims. That is, embodiments obtained by combining technical means appropriately modified within the scope of the claims are also included in the technical scope of the present invention.

  The present invention can also be applied to applications that perform microchemical processes using micromachining technology.

It is a figure which shows the structural example of the microchemical apparatus which concerns on this invention. It is a perspective view which shows the structure of a microchemical apparatus. It is sectional drawing which shows the structure of a microchemical apparatus. It is a perspective view which shows the structure of a microchemical apparatus. It is a figure which shows the structure of a microchemical apparatus. It is a figure which shows the mode of the sample from the time of the sample supply start in the adsorbent surface. It is a perspective view which shows the structure and coordinate axis of a microchemical apparatus. FIG. 8A shows the state of the dye on the adsorbent surface before separation and FIG. 8B shows the state after separation. It is a perspective view which shows the structure of a flat type device. It is a perspective view which shows the structure of a flat type device. FIG. 11A is a diagram showing the state of the dye on the adsorbent surface before separation and FIG. 11B is the diagram after separation. It is a figure which shows a Yxy color system. It is a figure which shows the result and the reference line which plotted x and y. It is a figure which shows the color intensity division | segmentation of a mixed color. It is a figure which shows the adsorbent surface image after the batch separation experiment in a Couette flow field. It is a figure which shows a mode that color intensity was plotted. It is a figure which shows the adsorbent surface image after the batch separation experiment in a Couette flow field. It is a figure which shows a mode that color intensity was plotted. It is a figure which shows the assumed column shape and speed profile. It is a figure which shows a capacity | capacitance coefficient. It is a figure which shows the calculation method of the capacity | capacitance coefficient of a blue dye. It is a figure which shows the calculation method of the capacity | capacitance coefficient of red dye. It is a figure which shows theoretical plate height as a batch separation experiment result in a Couette flow field. It is a figure which shows the theoretical plate height in the isolation | separation of a shear drive type chromatography. It is a figure which shows theoretical plate height as a batch-separation experiment result in a Poiseuille flow field. It is a figure which shows theoretical plate height about a blue dye as a batch separation experiment result. It is a figure which shows theoretical plate height as a batch separation experiment result about a red dye. It is a figure which shows the dependence to the channel thickness and adsorbent film thickness of theoretical height. It is a figure which shows the adsorbent surface image after a continuous separation experiment. It is a figure which shows a dimensionless density distribution. It is a figure which shows a molecular diffusion coefficient. It is a figure which shows the estimation result of a sample locus | trajectory. It is a figure which shows the estimation result of a dimensionless density distribution. It is a figure which shows a dimensionless density distribution. It is a figure which shows a sample locus | trajectory. It is a figure which shows the result of having plotted the color intensity on a line. It is a figure which shows the adsorbent surface image after a continuous separation experiment. It is a figure which shows the adsorbent surface image after a continuous separation experiment. It is a top view which shows arrangement | positioning of the thin film of a mixing separation mode device. It is a top view which shows arrangement | positioning of the thin film of a reaction separation device. 41 (a) and 41 (b) show the arrangement of the device sample and the eluent supply port, and FIG. 41 (a) is a plan view showing the adsorbent film on the surface of the rotating plate. FIG. 41B is a perspective view showing the configuration of the fixing plate. It is sectional drawing which shows the structure of a microchemical apparatus. It is a top view which shows the structure of a microchemical apparatus. 44 (a) and 44 (b) show a schematic configuration of a conventional SDC apparatus, FIG. 44 (a) is a cross-sectional view showing a channel, and FIG. 44 (b) is an elution. It is sectional drawing which shows the structure of the flow direction of an agent. It is a perspective view which shows the schematic structure of the conventional CAC apparatus. It is a perspective view which shows the mode of isolation | separation in a mobile phase type | mold chromatographic separation apparatus. It is a perspective view which shows the mode of isolation | separation in a CAC apparatus.

Claims (2)

  A plate A having a plurality of parallel plates and having at least one sample inlet of the parallel plates and a plate B having an active substance on the surface thereof, the surface of the plate B having an active substance faces the plate A. A scientific apparatus having a function of being arranged together and capable of rotating at least one of the plates A or B, and having a product outlet on the outer periphery of the plate A or B. Separated using scientific apparatus according to claim 1, is present in the phase opposite the parallel plate of the sample, one or the products resulting from the sample by shear stress generated by rotating both of the parallel plates to each other A separation method characterized by:

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