Patent Description:
For example, Japanese Patent Application Laid-Open (<CIT> describes a high-speed liquid chromatography filter in which a coupling member is fitted over a column body so as to house a column filter in a space in the coupling member. The column filter is configured including an outer filter layer with a large pore size, and an inner filter layer with a small pore size.

Filter devices that include plural filters with different pore sizes to each other are employed in order to prevent filter clogging over a long period of time. However, even in cases in which plural filters with different pore sizes are employed, filter clogging may still occur in a short period of time, requiring filter replacement.

<CIT> discloses a chromatography column.

<CIT> discloses a prefilter element for a continuous flow system such as a liquid chromatography cartridge.

<CIT> discloses a filter device for a liquid chromatograph, wherein the downstream filter has a smaller pore size than the upstream filter.

<CIT> discloses a column for liquid chromatography having a sealing member formed between a first frit and a second frit, the frits having filters comprising different pore sizes.

An object of the present invention is to suppress filter clogging in a configuration including plural filters.

The present invention provides a column as claimed in claim <NUM>. The column includes: a filter device comprising: a first filter; a first retaining member that has a hollow shape, the first filter being fitted inside the first retaining member; a second filter; a second retaining member that is disposed downstream of the first filter and that has a hollow shape, the second filter being fitted inside the second retaining member; and a spacer that has a hollow shape, that is disposed between the first retaining member and the second retaining member, and that maintains a non-contact state between the first filter and the second filter, and that includes a first contact portion contacting the first filter; wherein the column further comprises a column body that is filled with a filler to separate a component contained in a sample that is filtered by the filter device; characterized in that: the second filter has a smaller pore size than the first filter; and a thickness T of the spacer is, with respect to a pore size D of the first filter, within a range satisfying a relationship D × <NUM> ≤ T ≤ <NUM>.

In this column, the second filter that is fitted inside the second retaining member has a smaller pore size than the first filter that is fitted inside the first retaining member. The second retaining member is disposed downstream of the first filter, and so the second filter is also disposed downstream of the first filter. When a filtration subject flows from the first filter to the second filter, of foreign material contained in the filtration subject, foreign material that has a relatively large particle size can be removed by the first filter, and then foreign material that has a relatively small particle size can be removed by the second filter.

The spacer is disposed between the first retaining member and the second retaining member. The spacer maintains the non-contact state between the first filter and the second filter. Since the first filter and the second filter do not contact each other, a contact portion with holes that are smaller than the pore size of the first filter and the pore size of the second filter is not formed. Thus, foreign material that is smaller than the pore sizes of these filters is suppressed from becoming trapped at the portion between the first filter and the second filter, such that clogging is suppressed.

The spacer includes the first contact portion that contacts the first filter. Thus, movement of the first filter toward the second filter is suppressed by the first contact portion. This enables the non-contact state between the first filter and the second filter to be maintained, enabling the advantageous effect of suppressing clogging between the first filter and the second filter to be maintained.

The first contact portion may be provided around the entire circumference of an inner ring of the spacer.

When contact tabs are provided to the entire circumference of the inner ring of the spacer, movement of the first filter toward the second filter can be suppressed around the entire inner circumference of the spacer.

The first contact portion may be provided in a ring shape by setting an internal diameter of the spacer smaller an internal diameter of the first retaining member.

The ring shaped first contact portion can be provided simply by setting the internal diameter of the spacer smaller than the internal diameter of the first retaining member, such that there is no need to form the spacer in a complex shape.

The first contact portion may protrude from a portion of an inner ring circumference of the spacer toward the radial direction inside.

When the first contact portion protrudes from a portion of the inner ring circumference of the spacer toward the radial direction inside, the spacer is not provided around the entire inner circumference of the spacer. This enables a greater flow path area at the radial direction inside of the spacer, namely a greater area allowing a filtration subject to pass through, to be secured.

A thickness T of the spacer is set with respect to a pore size D of the first filter within a range satisfying the relationship D × <NUM> ≤ T ≤ <NUM>.

Setting the thickness T of the spacer with respect to the pore size D of the first filter so as to satisfy the relationship D × <NUM> ≤ T achieves a sufficient spacing between the first filter and the second filter, enabling a space in which the filtration subject that has passed through the first filter can flow to be secured.

Moreover, setting the thickness T of the spacer so as to satisfy the relationship T ≤ <NUM> enables the spacer to be suppressed from becoming excessively thick. Moreover, for example, in cases in which the spacer is employed as a column including a column body that separates a component in a sample being filtered as the filtration subject filtered by the filter device passes through, a decrease in separation precision of the component in the sample in the column body can be suppressed.

The first filter and the first retaining member may both be made from resin.

When the first filter and the first retaining member are both made from resin, the first filter can easily be fitted into and retained by the first retaining member.

A third filter that is disposed upstream of the first retaining member and that has a larger pore size than the pore size of the first filter may be included.

The third filter that has a larger pore size than that of the first filter enables foreign material with a large particle size to be removed from the filtration subject.

The third filter is preferably thinner than the first filter.

If the third filter were to have a larger pore size but the first filter and the third filter were to have the same thickness, the third filter would have a larger space formed at the inside of the filter. Thus, by setting the third filter with the thinner thickness, spreading out that occurs as eluent and sample flow through the space inside the third filter can be kept to a minimum.

The third filter is preferably a depth filter.

A depth filter traps foreign material not only at the surface but also inside the filter, such that clogging is less liable to occur.

The third filter preferably contacts a filtration face of the first filter.

The third filter is supported by the first filter, thereby enabling slipping and deformation of the third filter to be suppressed.

By including any one of the above-described filter devices in the column, the filter device suppresses filter clogging. Moreover, a component in the sample from which the foreign material has been removed by the filter device can be separated by the column body. Viewed from a second aspect of the present invention there is provided a liquid chromatography device as claimed in claim <NUM>. The liquid chromatography device is configured including the above-described column, an eluent supply device configured to supply an eluent to the column to separate the component, and a detection device configured to detect the component of the sample separated in the column.

The above-described column provided with any one of the above-described filter devices is included. Filter clogging is thereby suppressed by the filter device. A component in the sample in the column can be separated by supplying the eluent to the column using the eluent supply device. The separated sample component can be detected by the detection device.

The present invention enables filter clogging in a configuration including plural filters to be suppressed.

Explanation follows regarding a filter device, a column, and a liquid chromatography device of a first exemplary embodiment, with reference to the drawings. In this explanation, as an example the liquid chromatography device provided with the filter device is employed to measure the concentration of glycated hemoglobin (HbA1c) in whole blood. However, the measurement subject is not limited thereto, and moreover the filter device may be applied to devices other than the liquid chromatography device.

As illustrated in <FIG>, a blood collection tube <NUM> is set in a device body <NUM> of a liquid chromatography device <NUM>. The liquid chromatography device <NUM> is capable of automatically measuring the concentration of glycated hemoglobin (HbA1c) in whole blood.

The device body <NUM> of the liquid chromatography device <NUM> includes plural (five in the example illustrated in <FIG>) eluent bottles 18A, 18B, 18C, 18D, 18E. The eluent bottles 18A to 18E hold eluents A to E to be supplied to an analysis column <NUM>, described later. Each of the eluents has a different composition, component ratio, acidity level, osmotic pressure, or the like, according to the purpose.

The device body <NUM> further includes a sample preparation unit <NUM>, an analysis unit <NUM>, and a light measuring unit <NUM>.

The blood collection tube <NUM> is retained by the device body <NUM>. The blood collection tube <NUM> is moved to a position from which a sample can be taken using a nozzle <NUM> of the sample preparation unit <NUM>.

The sample preparation unit <NUM> includes the nozzle <NUM>, and a dilution tank <NUM>. The sample preparation unit <NUM> takes a sample of the blood in the blood collection tube <NUM> and introduces this blood to the dilution tank <NUM>. The blood diluted in the dilution tank <NUM> is then introduced to the analysis column <NUM>.

The nozzle <NUM> is capable of sucking in and expelling liquid, and may be applied to various liquids, in particular a blood sample from the blood collection tube <NUM>. The nozzle <NUM> can use suction to take a sample of the liquid, and can then expel the liquid.

The analysis unit <NUM> includes the analysis column <NUM>, a manifold <NUM>, a liquid feeding pump <NUM>, and an injection valve <NUM>.

As illustrated in <FIG> and <FIG>, the analysis column <NUM> includes a substantially circular cylinder shaped column body <NUM>, and an upstream filter structure <NUM> and a downstream filter structure <NUM>, respectively provided at the two axial direction (length direction, arrow L1 direction) ends of the column body <NUM>. The upstream filter structure <NUM> is an example of a "filter device". A sample flows through the inside of the analysis column <NUM> in the arrow F1 direction. "Upstream" and "downstream" refer to upstream and whole blood downstream in this flow direction.

A filler is retained inside the column body <NUM> in order to cause selective adsorption of hemoglobin in the sample. For example, a methacrylic acid/methacrylic acid ester copolymer may be employed as the filler.

The analysis unit <NUM> controls adsorption and desorption of biogenic components by the filler in the analysis column <NUM>, and supplies various biogenic components separated in the analysis column <NUM> to the light measuring unit <NUM>. As an example, the analysis unit <NUM> is set to a temperature in the region of <NUM>.

The manifold <NUM> is connected to the eluent bottles 18A, 18B, 18C, 18D, 18E via respective tubes 80A to 80E, and is connected to the injection valve <NUM> by a tube <NUM> with the liquid feeding pump <NUM> interposed between the manifold <NUM> and the injection valve <NUM>. The manifold <NUM> switches internal valves so as to selectively supply eluent to the analysis column <NUM> from a specific eluent bottle out of the plural eluent bottles 18A to 18E.

The liquid feeding pump <NUM> is provided partway along the tube <NUM>, and imparts a motive force in order to move the eluent to the injection valve <NUM>.

The injection valve <NUM> includes plural entry ports and exit ports (not illustrated in the drawings), and is capable of taking an introduction sample of a fixed quantity, and of introducing such an introduction sample into the analysis column <NUM>.

An injection loop <NUM> is connected to the injection valve <NUM>. The injection loop <NUM> is capable of retaining a fixed quantity (for example several µL) of liquid. Switching the injection valve <NUM> as appropriate enables selection of either a state in which the injection loop <NUM> is in communication with the dilution tank <NUM> and the introduction sample is supplied from the dilution tank <NUM> to the injection loop <NUM>, or a state in which the injection loop <NUM> is in communication with the analysis column <NUM> via a tube <NUM> and the introduction sample is introduced to the analysis column <NUM> from the injection loop <NUM>. For example, a six-way valve may be employed as the injection valve <NUM>.

The light measuring unit <NUM> is connected to a waste liquid tank <NUM> via a tube <NUM>. Liquid discharged from the analysis column <NUM> is discarded in the waste liquid tank <NUM>. The light measuring unit <NUM> optically detects the hemoglobin contained in the eluent that has passed through the analysis column <NUM>.

The upstream filter structure <NUM> of the analysis column <NUM> includes a first retaining member <NUM> and a second retaining member <NUM>, as illustrated in <FIG> and <FIG>. The first retaining member <NUM> is a hollow ring-shaped member, and a first filter <NUM> is retained in a hollow portion at the radial direction inside of the first retaining member <NUM>. The second retaining member <NUM> is a hollow ring-shaped member that has substantially the same external diameter, internal diameter, and thickness (liquid feed direction length) as the first retaining member <NUM>. A second filter <NUM> is retained in a hollow portion at the radial direction inside of the second retaining member <NUM>. The first filter <NUM> is disposed upstream of the second filter <NUM>. Namely, the first filter <NUM> is disposed closer to the inlet of the analysis column <NUM>. As an example, the first filter <NUM> and the second filter <NUM> are configured by membrane filters or sintered filters configured to trap particles on their filter surfaces. Note that the first retaining member <NUM> and the second retaining member <NUM> do not necessarily have the same thickness as each other.

As described above, in the present exemplary embodiment, the first retaining member <NUM> and the second retaining member <NUM> have substantially the same external diameter R1, and substantially the same internal diameter R2 and thickness. The first retaining member <NUM> and the second retaining member <NUM> are housed snugly in internal spaces of caps <NUM>, <NUM>, described later. Moreover, in the present exemplary embodiment, the first retaining member <NUM> and the second retaining member <NUM> are both made from resin.

As illustrated in <FIG>, the first filter <NUM> is formed with numerous percolation holes <NUM>, each having a specific pore size D. The second filter <NUM> is formed with numerous percolation holes <NUM>, each having a pore size E that is smaller than that of the percolation holes <NUM> in the first filter <NUM>. Note that although the pore size D and the pore size E are respectively illustrated as uniform diameters in <FIG>, in reality variation within a specific range may be present in the pore size D and the pore size E of the first filter <NUM> and the second filter <NUM>. However, the pore size E of the percolation holes <NUM> in the second filter <NUM> is smaller than the particle size of the filler in the column body <NUM>. Liquid introduced to the analysis column <NUM> by the pump passes through the first filter <NUM>, and then passes through the second filter <NUM>. As will be described later, in the present exemplary embodiment, a filtration subject flows from the first filter <NUM> that has the larger pore size to the second filter <NUM> that has the smaller pore size. Namely, the second filter <NUM> that has the smaller pore size is a filter disposed downstream of the first filter <NUM> that has the larger pore size.

In the present exemplary embodiment, the first filter <NUM> is configured by a porous resin (sintered resin product), and more specifically, is made of polyethylene. The resin first filter <NUM> is thus fitted inside and retained by friction in the hollow portion at the radial direction inside of the first retaining member <NUM> that is also made of resin. The outer side of the first filter <NUM> is surrounded by the first retaining member <NUM>. The thickness of the first filter <NUM> is the same as the thickness of the first retaining member <NUM>.

In the present exemplary embodiment, the second filter <NUM> is also configured by a porous resin (sintered resin product), and more specifically, is made of polyether ether ketone. The resin second filter <NUM> is thus fitted inside and retained by friction in the hollow portion at the radial direction inside of the second retaining member <NUM> that is also made of resin. The thickness of the second filter <NUM> is the same as the thickness of the second retaining member <NUM>.

A spacer <NUM> is disposed between the first retaining member <NUM> and the second retaining member <NUM>. The spacer <NUM> is a hollow ring-shaped member that has a specific thickness T (described in detail later). The spacer <NUM> contacts both the first retaining member <NUM> and the second retaining member <NUM>. In the present exemplary embodiment, the spacer <NUM> is made of resin.

An external diameter R3 of the spacer <NUM> is substantially the same as the external diameter R1 of the first retaining member <NUM> and the external diameter R1 of the second retaining member <NUM>. However, an internal diameter R4 of the spacer <NUM> is smaller than the internal diameter R2 of the first retaining member <NUM>. A radial direction inside portion of the spacer <NUM>, more specifically a portion of the spacer <NUM> that is positioned further toward the radial direction inside than the internal diameter R2 of the first retaining member <NUM>, is positioned further toward the inside than an inner ring edge (a radial direction inside edge of the ring shaped portion) of the first retaining member <NUM>, and is in contact with a downstream end face of the first filter <NUM>.

As is also illustrated in <FIG>, in the first exemplary embodiment, the spacer <NUM> includes a first contact portion <NUM> that contacts the first filter <NUM> around the entire inner circumference of the spacer <NUM>. In other words, the internal diameter R4 of the spacer <NUM> is smaller than the internal diameter R2 of the first retaining member <NUM>, and thus the first contact portion <NUM> is a ring shaped portion including the inner ring edge of the spacer <NUM> (radial direction inside edge of the ring shaped portion) and serves as an example of a contact tab. In the present exemplary embodiment, the first contact portion <NUM> also contacts an upstream end face of the second filter <NUM>.

As illustrated in <FIG>, the downstream filter structure <NUM> includes a ring shaped downstream retaining member <NUM>, and a downstream filter <NUM> is retained clamped between the column body <NUM> and the downstream retaining member <NUM>. Numerous percolation holes formed in the downstream filter <NUM> with a specific pore size have a pore size smaller than the particle size of the filler, such that the downstream filter <NUM> prevents the filler inside the column body <NUM> from being discharged to the exterior.

A third filter <NUM> is disposed further upstream than the upstream filter structure <NUM>. The third filter <NUM> is a depth filter in which a fibrous material is interwoven so as to form a filter structure, and traps foreign material in the filtration subject not only at the filter surface but also in tortuous internal passages. This discourages clogging even if the filtration precision has dropped. The pore size (mesh size) of the third filter <NUM> is larger than the pore size of the first filter <NUM>, and the thickness (liquid feed direction length) of the third filter <NUM> is thinner than that of the first filter <NUM> and the second filter <NUM>. As an example, the first filter <NUM> and the second filter <NUM> each have a thickness of from <NUM> to <NUM>, and the third filter <NUM> has a thickness of from <NUM> to <NUM>. Since the third filter <NUM> is thinner than the first filter <NUM>, spreading out that occurs as the eluent and sample flows through a space inside the third filter <NUM> can be kept to a minimum.

As illustrated in <FIG>, the third filter <NUM> is attached to the first retaining member <NUM>, and contacts the first filter <NUM> on the upstream side of the first filter <NUM>. In other words, the first filter <NUM> configures a structure downstream of the third filter <NUM> that supports the third filter <NUM> by contacting the entire downstream face of the third filter <NUM>. Namely, a filtration face of the third filter <NUM> is in contact with the first filter <NUM>. In the present exemplary embodiment, the third filter <NUM> is a filter configured by a resin nonwoven fabric. Although it is difficult to fix the filter edge of a thin filter using a retaining member or the like without causing a reduction in the effective filtration surface area, in the present exemplary embodiment, the downstream face of the third filter <NUM> and the first filter <NUM> are in contact with one another, such that the third filter <NUM> is pressed against the first filter <NUM> by the flow of liquid, thus fixing the third filter <NUM>. Since the third filter <NUM> is a depth filter with large pores, the likelihood of blocked pores arising in the first filter <NUM> at a contact location between the third filter <NUM> and the first filter <NUM> is low, and clogging therefore does not occur.

The caps <NUM>, <NUM> are respectively mounted to the upstream side and downstream side of the column body <NUM> by being screwed into place. The upstream filter structure <NUM> is retained gripped between the column body <NUM> and the cap <NUM>, and the downstream filter structure <NUM> is retained gripped between the column body <NUM> and the cap <NUM>. The downstream face of the second filter <NUM> is in contact with the filler retained in the column body <NUM>. Each of the caps <NUM>, <NUM> is formed with a flow path <NUM> through which the sample flows. The column body <NUM> and the respective filters are integrated together in order to form the analysis column <NUM>. This enables effort required when replacing the column body <NUM> and the respective filters to be alleviated.

Explanation follows regarding operation of the present exemplary embodiment.

In the liquid chromatography device <NUM> illustrated in <FIG>, the nozzle <NUM> is used to take a blood sample from the blood collection tube <NUM>, and this blood sample is supplied to the dilution tank <NUM>. A diluent solution is also supplied to the dilution tank <NUM> from a preparation liquid tank (not illustrated in the drawings) in order to prepare an introduction sample in the dilution tank <NUM>.

The introduction sample prepared in the dilution tank <NUM> is supplied into and retained in the injection loop <NUM>. The injection valve <NUM> is then switched so as to introduce the sample retained in the injection loop <NUM> into the analysis column <NUM>. When the sample is introduced into the analysis column <NUM>, components including sA1c, HbA0, and mutant Hb are adsorbed by the filler. The injection valve <NUM> is then switched as appropriate so as to sequentially supply the eluents A to E into the analysis column <NUM> according to a predetermined control sequence.

The eluent containing the various types of separated hemoglobin is then discharged from the analysis column <NUM>. The eluent is supplied via a tube <NUM> to a light measuring cell of the light measuring unit <NUM>, and is then guided via the tube <NUM> to the waste liquid tank <NUM>.

In the light measuring unit <NUM>, light from a light source is shone consecutively on the eluent. Transmitted light that has passed through the eluent is split using a beam splitter and picked up by light receiving elements. A chromatogram is computed and obtained by a control section of the light measuring unit <NUM> based on the light reception results of the light receiving elements.

The upstream filter structure <NUM> of the analysis column <NUM> of the present exemplary embodiment includes the third filter <NUM>, the first filter <NUM>, and the second filter <NUM> in sequence from the liquid feed direction upstream side. The filter pore size of these filters decreases on in sequence from the upstream side toward the downstream side. Accordingly, larger sized foreign material is removed in sequence from the upstream side.

The upstream side of the column body <NUM> is contacted by the second filter <NUM>, thus suppressing the filler in the column body <NUM> from escaping (leaking) upstream.

The spacer <NUM> is disposed between the first retaining member <NUM> that retains the first filter <NUM> and the second retaining member <NUM> that retains the second filter <NUM>. The spacer <NUM> creates a non-contact state between the first filter <NUM> and the second filter <NUM>, such that a space is created between the first filter <NUM> and the second filter <NUM>.

Note that <FIG> schematically illustrates the percolation holes <NUM> of the first filter <NUM>. Similarly, <FIG> schematically illustrates the percolation holes <NUM> of the second filter <NUM>. Note that although the shapes of the percolation holes <NUM>, <NUM> are approximated to true circles in <FIG>, <FIG>, and <FIG>, described later, in reality elliptical holes or polygonal holes may also be present.

At a boundary location between the first filter <NUM> and the second filter <NUM>, the percolation holes <NUM> of the first filter <NUM> illustrated in <FIG> and the percolation holes <NUM> of the second filter <NUM> illustrated in <FIG> would overlap each other. As illustrated in <FIG>, such overlapping of the percolation holes <NUM> and the percolation holes <NUM> would form fine holes <NUM> each having a smaller pore size than the pore size of the percolation holes <NUM>. Since foreign material would pass through the fine holes <NUM> less readily than through the percolation holes <NUM> due to the smaller opening area, clogging would be liable to occur at the boundary location between the first filter <NUM> and the second filter <NUM>. Such clogging would reduce the effective filtration surface area of the filters, which would for example lead to a drop in flow speed and an increase in the pressure of the sample being filtered.

To address this, in the present exemplary embodiment, the spacer <NUM> is used to create the non-contact state between the first filter <NUM> and the second filter <NUM>. Since there is no boundary location between the first filter <NUM> and the second filter <NUM>, locations (the fine holes <NUM> illustrated in <FIG>) having a smaller opening area than the percolation holes <NUM> do not arise. Accordingly, the present exemplary embodiment is capable of suppressing clogging of the first filter <NUM> and the second filter <NUM>. Suppressing such clogging enables a drop in the filtration performance of the filter device to be suppressed, and moreover enables increases in the lifespans of the first filter <NUM> and the second filter <NUM>.

Moreover, in the upstream filter structure <NUM> of the present exemplary embodiment, the spacer <NUM> is provided with the first contact portion <NUM>. The first contact portion <NUM> contacts the downstream face of the first filter <NUM>. Accordingly, even if the first filter <NUM> is pushed toward the downstream side by the flow of the sample being filtered in the arrow F1 direction (see <FIG>), the first filter <NUM> is suppressed from slipping or detaching from the first retaining member <NUM>, enabling the spacing between the first filter <NUM> and the second filter <NUM> to be maintained. For example, the first filter <NUM> can be suppressed from moving downstream and contacting the second filter <NUM>. Maintaining the spacing between the first filter <NUM> and the second filter <NUM> achieves such effects as suppressing a reduction in the filtration performance of the filter device, and increasing the lifespans of the first filter <NUM> and the second filter <NUM>. Moreover, a second contact portion (not illustrated in the drawings) is provided on the opposite face to the first contact portion <NUM>, and the second contact portion contacts the upstream face of the second filter <NUM>. Although the second contact portion may be omitted since the spacer <NUM> is upstream of the second filter <NUM>, such a second contact portion is capable of preventing the second filter <NUM> from slipping or detaching from the second retaining member <NUM>.

As illustrated in <FIG>, the upstream filter structure <NUM> of the present exemplary embodiment includes the third filter <NUM> that is provided further upstream than the first filter <NUM>. The third filter <NUM> covers the first filter <NUM>, and the pore size (mesh size) of the third filter <NUM> is larger than the pore size D of the percolation holes <NUM> of the first filter <NUM>. This enables foreign material with a relatively large particle size to be removed from the sample being filtered first, by the third filter <NUM>. Foreign material with a smaller particle size can then removed by the first filter <NUM>, and foreign material with an even smaller particle size can then removed by the second filter <NUM>.

The third filter <NUM> is further upstream than the first filter <NUM>, and contacts the first filter <NUM>. The first filter <NUM> therefore supports the third filter <NUM>, enabling the third filter <NUM> to be suppressed from slipping toward the downstream side or deforming due to the flow of the sample being filtered in the arrow F1 direction. For example, since the third filter <NUM> is configured from nonwoven fabric, the third filter <NUM> flexes easily. However, since the third filter <NUM> contacts and is supported by the filtration face of the first filter <NUM>, flexing of the third filter <NUM> is suppressed.

Note that the thickness T of the spacer <NUM> is not limited, as long as the thickness T is sufficient to place the first filter <NUM> and the second filter <NUM> in the non-contact state as described above. However, a lower limit for the thickness T of the spacer <NUM> is set with respect to the pore size D (mm) of the percolation holes <NUM> of the first filter <NUM> so as to satisfy the relationship D × <NUM> ≤ T. So doing achieves a sufficient spacing between the first filter <NUM> and the second filter <NUM>. The resulting gap enables, for example, a space in which the filtration subject that has passed through the first filter <NUM> can flow to be secured. This configuration is preferable since any obstruction to the flow of eluent can be suppressed even if foreign material contained in the filtration subject is trapped at the surface of the second filter <NUM>.

Moreover, an upper limit of the thickness T of the spacer <NUM> is set so as to satisfy the relationship T ≤ <NUM>. With increasing flow path length to the column body <NUM>, the sample spreads out more before reaching the column body <NUM>, resulting in decreased separation precision. However, setting the thickness T of the spacer <NUM> within the above range enables good separation precision to be maintained. Moreover, in the present exemplary embodiment, since the upstream filter structure <NUM> is employed to remove foreign material from the sample flowing into the column body <NUM>, an increase in pressure in the column body <NUM> can be prevented, enabling a decrease in separation precision to be suppressed.

The foregoing explanation describes the first contact portion <NUM>, formed in a ring shape at a radial direction inside portion of the spacer <NUM> by setting the internal diameter R4 of the spacer <NUM> smaller than the internal diameter R2 of the first retaining member <NUM>, as an example of the first contact portion provided to the spacer <NUM>. However, since it is sufficient that the first contact portion <NUM> contact the first filter <NUM>, the first contact portion <NUM> is not limited to the shape and placement described above. For example, the first contact portion <NUM> may be configured by protruding tabs as illustrated in <FIG>.

In a first modified example illustrated in <FIG>, protruding tabs <NUM> are formed protruding from the inner circumference of the spacer <NUM> toward the radial direction inside at two opposing locations. In the first modified example, the internal diameter R4 of the spacer <NUM> is equal to the internal diameter R2 of the first retaining member <NUM>. Accordingly, the first contact portion can be formed with a simple structure by the protruding tabs <NUM> protruding from the inner circumference of the spacer <NUM> in this manner.

In a second modified example illustrated in <FIG>, the protruding tabs <NUM> of the first modified example illustrated in <FIG> protrude from the inner circumference of the spacer <NUM> toward the radial direction inside at four locations. In the second modified example illustrated in <FIG>, since the number of the protruding tabs <NUM> is greater, the effect of suppressing slipping and detachment of the first filter <NUM> is greater than that of the first modified example illustrated in <FIG>. On the other hand, in the first modified example illustrated in <FIG>, since the number of the protruding tabs <NUM> is fewer than in the second modified example illustrated in <FIG>, a smaller overall area of the percolation holes of the first filter <NUM> is blocked by the protruding tabs <NUM>, thus enabling a greater flow path area to be secured in practice. Even the second modified example illustrated in <FIG> in which four of the protruding tabs <NUM> are formed is capable of securing a greater flow path area than the first contact portion <NUM> having the shape illustrated in <FIG>.

In a third modified example illustrated in <FIG>, a bridging tab <NUM> is provided spanning across the diameter of the inner circumference of the spacer <NUM>. In other words, the bridging tab <NUM> has a shape achieved by extending the two protruding tabs <NUM> of the first modified example illustrated in <FIG> in their protruding directions until they join up. The flow speed of the filtration subject flowing through the radial direction inside of the first retaining member <NUM> is faster the closer it is to a radial direction central portion thereof. The bridging tab <NUM> of the third modified example illustrated in <FIG> also contacts the first filter <NUM> at this central portion, and is thus highly effective in suppressing slipping and detachment of the first filter <NUM>.

By contrast, in the first contact portion <NUM> in the example illustrated in <FIG>, the first contact portion <NUM> contacts the first filter <NUM> around its entire circumference, and is thus capable of suppressing slipping and detachment of the first filter <NUM> around its entire circumference. Since the first contact portion <NUM> can be formed simply by reducing the internal diameter R4 of the spacer <NUM>, there is no need to form the protruding tabs <NUM> or the bridging tab <NUM> and the shape remains simple. Note that the modified examples of the first contact portion may similarly be adopted for the second contact portion. The first contact portion and the second contact portion do not have to have the same shape as each other. For example, the first contact portion <NUM> may have the shape described in the exemplary embodiment illustrated in <FIG>, whereas the second contact portion may have the shape of the first modified example illustrated in <FIG>.

The materials employed for the first retaining member <NUM>, the second retaining member <NUM>, the first filter <NUM>, and the second filter <NUM> are not limited to the resins described above, and for example some or all of these components may be configured from metal. When fitting the resin first filter <NUM> into the resin first retaining member <NUM>, the press fitting may incur some slight deformation (tightening) in order to achieve retention. In such cases, the first retaining member <NUM> and the first filter <NUM> responds to the deformation of the other thereof, enabling a seal to be formed at a tight fitting portion between the first retaining member <NUM> and the first filter <NUM>. Due to being made of resin, the second retaining member <NUM> and the second filter <NUM> have a similar relationship, such that the second retaining member <NUM> and the second filter <NUM> responds to the deformation of the other thereof, enabling a seal to be formed at a tight fitting portion between the two.

Claim 1:
A column (<NUM>) comprising:
a filter device (<NUM>) comprising:
a first filter (<NUM>);
a first retaining member (<NUM>) that has a hollow shape, the first filter (<NUM>) fitted inside the first retaining member (<NUM>); and
a second filter (<NUM>) that has a smaller pore size than the first filter (<NUM>);
wherein the column further comprises a column body (<NUM>) filled with a filler to separate a component contained in a sample that is filtered by the filter device (<NUM>);
characterized in that the filter device (<NUM>) comprises:
a second retaining member (<NUM>) that is disposed downstream of the first filter (<NUM>) and that has a hollow shape, the second filter (<NUM>) fitted inside the second retaining member (<NUM>); and
a spacer (<NUM>) that has a hollow shape, that is disposed between the first retaining member (<NUM>) and the second retaining member (<NUM>), that maintains a non-contact state between the first filter (<NUM>) and the second filter (<NUM>), and that includes a first contact portion (<NUM>) contacting the first filter (<NUM>);
wherein a thickness, T, of the spacer (<NUM>) is, with respect to a pore size, D, of the first filter (<NUM>), within a range satisfying a relationship D × <NUM> ≤ T ≤ <NUM>.