Micromachined flow cell with freestanding fluidic tube

Abstract

A micromachined flow cell includes a substrate and a freestanding tube, delimiting a fluidic conduit therein and being integrally formed from material of the substrate.

Claims

1. A flow cell, comprising: a substrate; and a freestanding tube delimiting a fluidic conduit therein and being integrally formed from material of the substrate, and surrounded by a gas atmosphere, wherein the freestanding tube comprises a section comprising a first end and a second end, and the section is configured for receiving electromagnetic radiation at the first end, and for emitting at the second end electromagnetic radiation having propagated through the fluidic conduit, and wherein the electromagnetic radiation coupled into the fluidic conduit undergoes total internal reflection at a boundary between an exterior surface of the freestanding tube and the surrounding gas atmosphere.

2. The flow cell according to claim 1, wherein the substrate and the freestanding tube are composed of the same material.

3. The flow cell according to claim 1, wherein the substrate comprises fused silica.

4. The flow cell according to claim 1, wherein the fluidic conduit has an internal volume in a range selected from the group consisting of: between 1 nl and 1000 nl, and between 10 nl and 100 nl.

5. The flow cell according to claim 1, wherein the substrate comprises a trench and two surface portions, and the freestanding tube extends along the trench and is connected to the two surface portions of the substrate delimiting the trench.

6. The flow cell according claim 5, wherein the freestanding tube between the two surface portions is U-shaped.

7. The flow cell according claim 5, wherein the substrate comprises two fluidic channels formed therein, and wherein each of the fluidic channels is directly fluidically coupled to a respective one of the two surface portions.

8. The flow cell according claim 7, wherein each of the two fluidic channels ends at a respective one of two fluidic interfaces of the substrate.

9. The flow cell according claim 8, wherein at least one of the two fluidic interfaces is spatially extended compared to the respective one of the two fluidic channels.

10. The flow cell according to claim 5, comprising a feature selected from the group consisting of: a cover sheet attached to a top surface of the substrate for capping the trench; a bottom sheet attached to a bottom surface of the substrate; and both of the foregoing.

11. The flow cell according to claim 1, further comprising a further substrate and a further freestanding tube delimiting a further fluidic conduit therein and being integrally formed from material of the further substrate, wherein the substrate and the further substrate are vertically stacked.

12. The flow cell according to claim 11, wherein the fluidic conduit is fluidically coupled to the further fluidic conduit.

13. The flow cell according to claim 11, wherein the substrate and the further substrate have the same external contour.

14. The flow cell according to claim 1, comprising at least one further freestanding tube delimiting at least one further fluidic conduit therein and being integrally formed from material of the same substrate as the freestanding tube.

15. The flow cell according to claim 14, wherein the at least one further fluidic conduit is fluidically connected in series with the fluidic conduit or is fluidically connected in parallel to the fluidic conduit.

16. The flow cell according to claim 14, wherein the at least one further fluidic conduit has another length than the fluidic conduit so that an effective interaction length (L1, L2) along which electromagnetic radiation propagating through the respective fluidic conduit interacts with a fluidic sample flowing through the respective fluidic conduit differs for the different fluidic conduits.

17. The flow cell according to claim 1, wherein the exterior surface the freestanding tube has a shape selected from the group consisting of: a rectangle, a circle, a hexagon, a polygon with rounded edges, and a shape of two parallel linear sections connected by two opposing curved sections.

18. The flow cell according to claim 1, wherein the freestanding tube comprises an inner surface having a shape selected from the group consisting of: a rectangle, a rectangle having rounded edges, a circle, and an oval.

19. The flow cell according to claim 1, comprising a feature selected from the group consisting of: the flow cell comprises a first optical coupler element at least partially integrated in the substrate so as to couple electromagnetic radiation via the first optical coupler element into the fluidic conduit; the flow cell comprises a second optical coupler element at least partially integrated in the substrate so as to couple electromagnetic radiation from the fluidic conduit into the second optical coupler element; and both of the foregoing.

20. The flow cell according to claim 1, comprising an electromagnetic radiation source adapted for generating an electromagnetic radiation beam and for coupling the electromagnetic radiation beam into the fluidic conduit.

21. The flow cell according to claim 20, comprising a feature selected from the group consisting of: the electromagnetic radiation source is configured for generating an optical light beam or an ultraviolet beam; the flow cell comprises an electromagnetic radiation detector configured for detecting the electromagnetic radiation beam after propagation through the fluidic conduit; the flow cell comprises an electromagnetic radiation detector configured for detecting the electromagnetic radiation beam after propagation through the fluidic conduit wherein the electromagnetic radiation detector comprises an optical light detector or an ultraviolet radiation detector; and a combination of two or more of the foregoing.

22. The flow cell according to claim 1, a feature selected from the group consisting of: the material of the freestanding tube is optically transparent; the flow cell is configured to conduct a fluidic sample with a high pressure; the flow cell is configured to conduct a fluidic sample with a pressure of at least 50 bar; the flow cell is configured to conduct a fluidic sample with a pressure of at least 100 bar; the flow cell is configured to conduct a liquid sample; the flow cell is configured as a microfluidic flow cell; the flow cell is configured as a nanofluidic flow cell; and a combination of two or more of the foregoing.

23. A fluidic device for measuring a fluidic sample, the fluidic device comprising: a fluid separating device configured for separating the fluidic sample; and a flow cell according to claim 1 in fluid communication with the fluid separating device and configured for receiving the separated fluidic sample from the fluid separating device.

24. The fluidic device according to claim 23, wherein the fluid separating device is integrated in a chip.

25. The fluidic device according to claim 24, wherein the chip comprises a plurality of bonded sheets being patterned so as to form a fluidic conduit for conducting the fluidic sample.

26. The fluidic device according to claim 23, wherein a fluidic conduit of the fluid separating device is configured for conducting the fluidic sample, and is brought in fluid communication with the fluidic conduit of the freestanding tube via a hole-to hole coupling.

27. The fluidic device according to claim 26, wherein the fluid separating device and the flow cell are each formed as planar structures connected to one another at main surfaces of the fluid separating device and the flow cell so as to provide the hole-to-hole coupling at the connected main surfaces.

28. The fluidic device according to claim 23, comprising a feature selected from the group consisting of: the fluid separating device is configured for retaining the fluidic sample being a part of a mobile phase and for allowing other components of the mobile phase to pass the fluid separating device; the fluid separating device comprises a chromatographic column for separating components of the fluidic sample; at least a part of the fluid separating device is filled with a fluid separating material; at least a part of the fluid separating device is filled with a fluid separating material, wherein the fluid separating material comprises beads having a size in the range of 1 m to 10 m; at least a part of the fluid separating device is filled with a fluid separating material, wherein the fluid separating material comprises beads having pores having a size in the range of 50 to 300 ; the flow cell is arranged downstream of the fluid separating device; the fluid separating device comprises a microstructured body and porous material covering at least a portion of a surface of the microstructured body; the fluidic device is configured as a fluid separation system for separating compounds of the fluidic sample; the fluidic device is configured to analyze at least one physical, chemical and/or biological parameter of at least one compound of the fluidic sample; the fluidic device comprises a device selected from the group consisting of: a sensor device, a test device for testing a device under test or a substance, a device for chemical, biological and/or pharmaceutical analysis, a capillary electrophoresis device, a liquid chromatography device, and an HPLC device, a gas chromatography device, and a gel electrophoresis device.

29. A method of manufacturing a flow cell by micromachining, the method comprising: providing a substrate; integrally forming, from material of the substrate, a freestanding tube such that the freestanding tube is surrounded by a gas atmosphere; and delimiting a fluidic conduit in the freestanding tube, wherein the freestanding tube comprises a section comprising a first end and a second end, and the section is configured for receiving electromagnetic radiation at the first end, and for emitting at the second end electromagnetic radiation having propagated through the fluidic conduit, and wherein the electromagnetic radiation coupled into the fluidic conduit undergoes total internal reflection at a boundary between an exterior surface of the freestanding tube and the surrounding gas atmosphere.

30. The method according to claim 29, wherein the method further comprises: providing a first substrate body and a second substrate body; forming a groove in each of the first substrate body and the second substrate body; bonding the first substrate body to the second substrate body with correspondingly aligned grooves so as to form the fluidic conduit by the aligned grooves and so as to form the substrate by the bonded substrate bodies.

31. The method according to claim 30, wherein the method further comprises forming a trench in the substrate by removing material of the substrate in such a way that the freestanding tube is constituted by non-removed material of the substrate.

32. The method according to claim 29, wherein the method further comprises forming two fluidic channels within the substrate and each being fluidically coupled to a respective end of the freestanding tube.

33. The method according to claim 32, wherein the method further comprises forming spatially extended end sections of the two fluidic channels at positions at which the fluidic channels extend out of the substrate.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanying drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs.

(2) FIG. 1 illustrates a three-dimensional view of a micromachined flow cell according to an exemplary embodiment of the invention together with two details thereof.

(3) FIG. 2 shows a partially exploded view of the micromachined flow cell of FIG. 1.

(4) FIG. 3 illustrates a detail of the flow cell of FIG. 1 focusing on the fluidic system of the flow cell.

(5) FIG. 4A illustrates a flow cell arrangement according to an exemplary embodiment of the invention in which two fluidic channels are guided in parallel along an electromagnetic radiation path defined by a common light source and a dual light detector.

(6) FIG. 4B illustrates a flow cell according to another exemplary embodiment of the invention in which two fluidic conduits are fluidically coupled in series so as to provide a first flow cell section with an electromagnetic radiation detection path being separate from another electromagnetic radiation detection path of a second flow cell section.

(7) FIG. 5 illustrates a fluidic system of a micromachined flow cell according to an exemplary embodiment of the invention.

(8) FIG. 6 shows a three-dimensional view of a micromachined flow cell according to an exemplary embodiment of the invention.

(9) FIG. 7 illustrates two cross-sectional views of a combined arrangement of a multi-layer chip with integrated chromatographic separation column and a plate-like micromachined flow cell according to an exemplary embodiment of the invention.

(10) FIG. 8 illustrates cross-sectional views of three freestanding tubes according to exemplary embodiments of the invention which may manufactured by applying different etching procedures.

(11) FIG. 9 illustrates a calotte-shaped fluidic interface between a micromachined flow cell according to an embodiment of the invention and a fluidic environment.

(12) FIG. 10 illustrates a cylindrically-shaped fluidic interface between a micromachined flow cell according to an embodiment of the invention and a fluidic environment.

(13) FIG. 11 is a plan view of a micromachined flow cell according to an exemplary embodiment of the invention defining an axis A-A.

(14) FIG. 12 illustrates different cross-sections of fused silica wafers processed during the manufacture of a micromachined flow cell according to an exemplary embodiment of the invention.

(15) FIG. 13 is a cross-sectional view of a micromachined flow cell according to an exemplary embodiment of the invention in which the freestanding tube has a rectangular interior surface and a rectangular exterior surface.

(16) FIG. 14 is a cross-sectional view of a micromachined flow cell according to another exemplary embodiment of the invention having a rounded rectangular or basically oval interior cross-section and a rectangular exterior cross-section.

(17) FIG. 15 is an overview of a micromachined flow cell according to an exemplary embodiment of the invention showing characteristic features thereof.

(18) FIG. 16 and FIG. 17 illustrate coverage of a flow cell according to an exemplary embodiment of the invention with cover plates.

(19) FIG. 18 is a liquid chromatography device having implemented a micromachined flow cell according to an exemplary embodiment of the invention.

(20) The illustration in the drawing is schematic.

(21) FIG. 1 illustrates a micromachined flow cell 100 according to an exemplary embodiment of the invention.

(22) The micromachined flow cell 100 comprises a plate-like substrate 102 made of fused silica material. FIG. 1 shows that the plate-like substrate 102 is constituted by two parallel aligned sub-plates 152, 154 both made of fused silica material and being bonded to one another. The two stacked wafers or sub-plates 152, 154 may for instance have a total thickness of 600 m or 1050 m. A fused silica tube 104 stands free, i.e. in a bridge-like manner, along an extension direction which is parallel to the main surfaces of the plate-like substrate 102. The freestanding tube 104 is thin-walled and sealingly delimits in its interior a hollow lumen or fluidic conduit (see reference numeral 800 in FIG. 8). The freestanding tube 104 is circumferentially surrounded by an air atmosphere. The freestanding tube 104 is furthermore integrally formed from fused silica material of the substrate 102 so that the substrate 102 and the freestanding tube 104 are inseparably formed of a single common material.

(23) As can furthermore be taken from FIG. 1, the substrate 102 has a swimming pool-like trench 106, wherein the freestanding tube 104 extends along and within the trench 106 and is connected only at two surface portions 116 and 118 to a vertical wall of the substrate 102 delimiting the trench 106. The freestanding tube 104 is basically U-shaped with two parallel straight legs and a further straight connection portion connecting the two legs to one another. Accordingly, also the lumen within the freestanding tube 104 is basically U-shaped.

(24) Moreover, the fused silica substrate 102 has two integrated and buried fluidic channels 120 and 122 formed therein. Each of the fluidic channels 120 and 122 is directly and seamlessly fluidically coupled via a respective one of the two surface portions 116, 118 to the lumen of the freestanding tube 104. Each of the two fluidic channels 120 and 122 ends at a respective one of two fluidic interfaces 124, 126 at which the buried fluid conduit penetrates an upper surface of the substrate 102. Each of the two fluidic interfaces 124, 126 is a spatially extended end section of the buried fluid conduit and is for example calotte-shaped. A supply capillary (not shown) configured for supplying a fluidic sample to be analyzed by the flow cell 100 is connectable to the fluidic interface 126. This fluidic sample will flow through the fluidic channel 120, the lumen in the freestanding tube 104 and the fluidic channel 122 before leaving the flow cell 100 through the fluidic interface 124 and a drain capillary (not shown) to be connected thereto. Hence, the fluidic sample takes a basically U-shaped flow path from reference numeral 126 via 120, 104, 122 and 124.

(25) Furthermore, a waveguide 130, a ball lens 160 and a further waveguide 163 are configured for coupling primary light of an appropriate wavelength range into the central section of the lumen of the freestanding tube 104. The primary light is emitted by a light source (not shown). A part of the further waveguide 163 is guided through the substrate 102, see reference numeral 112, and leaves the latter via an interface 108. In a similar way, after the primary light has interacted with the fluidic sample flowing through the central section of the lumen of the freestanding tube 104, the correspondingly generated secondary light propagates through a waveguide 164 (partially guided through the substrate 102, see reference numeral 114), a ball lens 162 and a further waveguide 132 to a light detector (not shown). Thus, the light propagates from light pipe or waveguide 130 through ball lens 160 via interface 108 and light coupler or waveguide 163 into the fluidic channel within the freestanding tube 104, and undergoes total internal reflection at the boundary between an exterior surface of the freestanding tube 104 and the surrounding air environment. Correspondingly, the flow cell 100 comprises optical fiber piece or waveguide 164 which is also partially integrated in the fused silica substrate 102 so as to couple light from the fluidic conduit into optical coupler element or waveguide 132. The secondary light leaves the flow cell 100 via waveguide 164 partly within the substrate 102, via the optional ball lens 162 and via the further waveguide 132 connected to the ball lens 162 for subsequent detection in a detecting element such as one or more photo cells which is not shown in FIG. 1.

(26) A detail of FIG. 1 shows that a cover plate 150 made of an optically transparent material such as glass is attached to the substrate 102 to cover the trench 106 and the freestanding tube 104.

(27) Another detail of FIG. 1 shows the rectangular shape of the freestanding tube 104.

(28) FIG. 2 shows the micromachined flow cell 100 of FIG. 1 with detached upper plate 154 to expose the fluidic channels 120, 122.

(29) FIG. 3 shows a further detail of the micromachined flow cell 100 of FIG. 1 and FIG. 2 with internal fluidic volumes. Furthermore, connection plugs 300, 302 are shown as a fluidic interface.

(30) FIG. 4A shows a flow cell arrangement 450 according to another exemplary embodiment of the invention. A first fluidic path is formed by a lumen in a first freestanding tube 104 extending between a fluid inlet port or fluidic interface 126 and a fluid outlet port or fluidic interface 124. In parallel thereto, a second freestanding tube 400 extends between a further fluid inlet port or fluidic interface 406 and a further fluid outlet port or fluidic interface 408. The freestanding tubes 104, 400 extend parallel to one another and have basically parallel electromagnetic radiation detection paths. The latter are formed by an electromagnetic radiation source 402 (two separate electromagnetic radiation sources are possible as well) emitting light or UV radiation to be coupled via a respective one of two supply tubes 410 (for instance in the form of an integrated light pipe) into the freestanding tubes 104, 400. After interaction of this light with already separated fractions of a fluidic sample flowing through a respective one of the freestanding tubes 104, 400, and after total internal reflection of the light at an outer boundary of the freestanding tubes 104, 400 the secondary light is guided via a respective one of two second coupling tubes 412 (for instance in the form of an integrated light pipe) to a respective one of two electromagnetic radiation detectors 404. Although not shown in FIG. 4A, further optical elements such as a grating, deflection mirrors, etc. can be implemented in the optical path. FIG. 4A hence shows a parallel flow cell detection architecture, wherein all detection paths may have the same path length at a relatively small pitch.

(31) In contrast to the parallel fluidic arrangement of FIG. 4A, FIG. 4B illustrates a serial flow cell arrangement 480 according to another exemplary embodiment of the invention. According to FIG. 4B, a first flow cell having a path length L1 is arranged upstream of a second, shorter flow cell with a path length L2<L1. The electromagnetic radiation path lengths of the two flow cells shown in FIG. 4B are different and are defined by electromagnetic radiation source 402, coupling tube 410 (for instance in the form of an integrated light pipe), further coupling tube 412 (for instance in the form of an integrated light pipe) and detector 404 for the first flow cell and are formed by an electromagnetic radiation source 482, a coupling tube 486 (for instance in the form of an integrated light pipe), a further coupling tube 488 (for instance in the form of an integrated light pipe) and a further detector 484 for the second flow cell. By combining a first flow cell having a relatively large path length L1 with a downstream arranged second flow cell having an effective length L2<L1, the range of sensitivity of the entire flow cell arrangement 480 may be extended. The reason for this is that the linear range of accuracy depends on the fluidic path length L1, L2. FIG. 4B shows a tandem flow cell, i.e. a serial arrangement of a large flow cell path length and a short flow cell path length, for an improved linear detection range.

(32) FIG. 5 again shows a fluidic path of the micromachined flow cell 100 of FIG. 1 according to an exemplary embodiment of the invention.

(33) FIG. 6 illustrates an overview of the micromachined flow cell 100 of FIG. 1 without protection cover.

(34) FIG. 7 shows a cross-section of a multi-layer chip 700 integrating a chromatographic separation column 708 and being functionally and structurally connected to a plate-shaped micromachined flow cell 100 according to an exemplary embodiment of the invention. The multi-layer chip 700 comprises a plurality of bonded sheets 702, 704 being patterned so as to form a fluidic conduit 740 for conducting the fluidic sample. Via the fluid outlet channel of the multi-layer chip 700, the fluidic sample with the already separated fractions is supplied for detection in the flow cell 100.

(35) Still referring to FIG. 7, a planar interface between the chip 700 having the chromatographic column 708 and the flow cell 100 is provided. Advantageously, a hole to hole coupling is realized as indicated by reference numeral 706. Such a hole to hole coupling between the chip 700 and the flow cell 100 is provided both at a fluidic input and at a fluidic output of the flow cell 100.

(36) The fluidic sample is supplied via fluidic conduit 740, as sample inlet, and is then separated in chromatographic separation column 708. After separation, the separated fluidic sample is supplied via hole to hole coupling to the flow cell device 100. An interface 710 between the separation chip 700 and the micromachined flow cell 100 may be realized by a microfluidic polymer structure. The arrangement of coupled components 700, 100 may be attached to a support such as an instrument hardware 714. Pressure seal forces are indicated schematically with reference numeral 716. After detection in the flow cell 100, the fluidic sample may be drained via drain hole 718.

(37) A side view 750 of the coupled separation chip 700 and micromachined flow cell 100 is also shown in FIG. 7. Here, a direct fiber coupling without ball lenses is shown. Alternatively, one or more ball lenses may be implemented as well in FIG. 7.

(38) FIG. 8 shows three different cross-sectional views of interior and exterior shapes of freestanding tubes delimiting a lumen 800. A desired embodiment of FIG. 8 can be selected by correspondingly adjusting the used etching procedure.

(39) A first embodiment 820 shown in FIG. 8 has an outer surface 802 shaped like a rectangle or square. An inner surface 804 is shaped as a rectangle or square as well.

(40) A second embodiment 840 shown in FIG. 8 has an outer surface 802 shaped as a rectangle or square and an inner surface 804 shaped as a circle or oval.

(41) A third embodiment 860 of FIG. 8 has an outer surface consisting of two parallel linear sections 802 connected by two opposing curved sections 802, and have an inner surface 804 shaped as a circle. The sharp exterior edges may be rounded by appropriate processing (particularly by etching), as indicated in FIG. 8 with dotted lines.

(42) FIG. 9 shows an example of a shape of a fluidic interface as the one denoted with reference numeral 706 above. The shown fluidic interface 900 has a first cylindrical section 902, a directly connected calotte shaped section 904 and a further cylindrical section 906. The embodiment of FIG. 9 can be obtained by an etching procedure. The first cylindrical section 902 relates to the separation chip 700, whereas the calotte shaped section 904 and the further cylindrical section 906 relate to the micromachined flow cell 100.

(43) FIG. 10 shows another example of a shape of a fluidic interface as the one denoted with reference numeral 706 above. This fluidic interface 1000 between an integrated flow cell and a fluidic environment has a first cylindrical section 1002 and a directly connected second cylindrical section 1004 having a different, here smaller, diameter than the first cylindrical section 1002. The embodiment of FIG. 10 can be manufactured by grinding material of the substrate and has the advantage of a low dead volume and a better purged volume. The first cylindrical section 1002 relates to the separation chip 700, whereas the second cylindrical section 1004 relates to the micromachined flow cell 100.

(44) FIG. 11 shows a plan view of an integrated flow cell according to an exemplary embodiment which is very similar to the one shown in FIG. 1. A line A-A is defined in FIG. 11.

(45) The various cross-sections shown in FIG. 12 are taken along this line A-A. These cross-sections relate to semi-finished products as obtained during a manufacturing process of producing a micromachined flow cell according to an exemplary embodiment of the invention. This process will be explained in the following in further detail.

(46) FIG. 12 shows a first cross-sectional view 1200 of a fused silica substrate 1202 being covered partially with a protection mask 1204 on specific surface portions thereof. The protection mask 1204 is patterned at an upper main surface of the substrate 1202.

(47) In order to obtain cross-sectional view 1210, an etching process is applied which removes material from surface portions of the substrate 1202 which are not protected by protection mask 1204. Cross-sectional view 1210 therefore shows the structure after a hydrofluoric acid (HF) etch of the exposed area. This procedural step can be used for defining wall thickness.

(48) As can be taken from cross-sectional view 1220, a further patterning procedure may expose another surface portion of the substrate 1202, i.e. may selectively remove material of the protection mask 1204. Subsequently, an etching procedure may be performed so as to form two deep grooves 1212 and one shallow groove 1222 in between.

(49) Starting from the structure according to the cross-sectional view 1220, the remaining protection mask 1204 may be removed by selective etching.

(50) The cross-sectional view 1230 can be obtained by bonding two substrates according to cross-sectional view 1220 (after removal of protection mask 1204) to one another. This forms interior fluidic channel 1234.

(51) Cross-sectional view 1240 is obtained from cross-sectional view 1230 by covering and opening lateral surface portions of the substrate 1202 with protection mask 1242.

(52) A subsequent etching process (HF-etching) defines a freestanding tube in a center separated from other remaining portions of the substrate 1202. Cross-sectional view 1250 shows the obtained structure after removal of the protection mask. Singularization of the individual structures may be carried out as well.

(53) The geometry of the freestanding tube of FIG. 12 is obtained by wet etching.

(54) FIG. 13 shows that a freestanding tube 1302 can have another shape when other etching procedures are applied. The shape according to FIG. 13 can be obtained by applying DRIE (Deep Reactive Ion Etching) for detection tube and release area, wherein a HF-etch can be used for a final release etching.

(55) FIG. 14 shows a freestanding tube 1352 with still another shape obtained by applying still a further etching procedure. To obtain the shape according to FIG. 14, a wet etch procedure is applied for an inner contour and DRIE is applied for an outer contour of the detection tube. The final release etch is carried out by a HF-etch.

(56) FIG. 15 shows another view of the micromachined flow cell 100 of FIG. 1 in which several features are highlighted. Feature 1 shows side machining of optical windows for coupling light in and out. Feature 2 shows machining of low dead volume fluidic access holes. Feature 3 shows bonding of protection windows for improved mechanical robustness. Feature 4 shows machining of mechanical references for easy exchange of flow cell devices.

(57) FIG. 16 shows as to how a cover plate 1600 is attached and connected to an upper surface of the micromachined flow cell 100 and as to how a bottom plate 1602 is attached and connected to a lower surface of the micromachined flow cell 100. Furthermore, protection windows are formed.

(58) FIG. 17 shows that only a portion of the upper surface of the micromachined flow cell is covered with the cover plate 1600.

(59) FIG. 18 depicts a general schematic of a liquid separation system 2700. A pump 2720as a mobile phase drivedrives a mobile phase through a separating device 2730 (such as a chromatographic column) comprising a stationary phase. A sampling unit 2740 can be provided between the pump 2720 and the separating device 2730 in order to introduce a sample fluid to the mobile phase. The stationary phase of the separating device 2730 is adapted for separating compounds of the sample liquid. A flow cell 100 as part of a detector is provided for detecting separated compounds of the sample fluid. A fractionating unit 2760 can be provided for outputting separated compounds of sample fluid.

(60) It should be noted that the term comprising does not exclude other elements or features and the term a or an does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should also be noted that reference signs in the claims shall not be construed as limiting the scope of the claims.