Abstract
Please add the following Abstract on a separate sheet after the claims section of the subject application.
An in-vitro diagnostic (IVD) analyzer 200 comprising at least one sensor 212 located in a flow-through sensor path 211 of detecting unit and requiring at least one oxygenated calibration fluid 221, 222 for calibration is herein disclosed. The IVD analyzer 200 further comprises a fluid-supply unit 220 comprising at least one deoxygenated calibration fluid 221, 222, a fluid-selection valve 230 and at least one oxygenation tubing 215, 216 having two ends connected to the fluid-selection valve 230 as a loop, wherein the oxygenation tubing 215, 216 comprises oxygen-permeable walls, and wherein the IVD analyzer 200 further comprises a pump 240 and a controller 250 configured to control the pump 240 and the fluid-selection valve 230 for transporting deoxygenated calibration fluid 221, 222 into the oxygenation tubing 215, 216, to wait a predetermined time required for oxygenation of the deoxygenated calibration fluid 221, 222 via oxygen uptake from ambient air through the tubing walls, and to transport the thereby obtained oxygenated calibration fluid 221, 222 into the sensor path 211 for calibration of the at least one sensor 212. A respective automatic method of calibrating at least one sensor 212 is herein also disclosed.
Claims
1. An in-vitro diagnostic (IVD) analyzer comprising at least one sensor located in a flow-through sensor path of a detecting unit involving a reaction with oxygen in a sample in order to determine a sample parameter and requiring at least one oxygenated calibration fluid with a certain level of oxygenation for calibration, the IVD analyzer further comprising a fluid-supply unit comprising at least one deoxygenated calibration fluid, a fluid-selection valve comprising one or more fluid input ports for selecting at least one fluid at a time, a common outlet port fluidically connected or connectable via a fluidic line to the sensor path, wherein the IVD analyzer further comprises at least one oxygenation tubing having two ends connected to the fluid-selection valve as a loop, wherein the oxygenation tubing comprises oxygen-permeable walls, and wherein the IVD analyzer further comprises a pump and a controller configured to control the pump and the fluid-selection valve for transporting deoxygenated calibration fluid from the fluid-supply unit into the oxygenation tubing, to wait a predetermined time required for oxygenation of the deoxygenated calibration fluid via oxygen uptake from ambient air through the tubing walls until the required level of oxygenation is obtained, and to transport the thereby obtained oxygenated calibration fluid into the sensor path for calibration of the at least one sensor.
2. The IVD analyzer according to claim 1, wherein the at least one sensor is a metabolite sensor including at least one of a glucose sensor and a lactate sensor.
3. The IVD analyzer according to claim 1, further comprising an oxygenation tubing for each different deoxygenated calibration fluid to be oxygenated.
4. The IVD analyzer according to claim 1, wherein the controller is further configured to control the pump and the fluid-selection valve to transport any other fluid from the fluid-supply unit into the sensor path while the at least one oxygenation tubing is fluidically isolated and the deoxygenated calibration fluid is being oxygenated.
5. The IVD analyzer according to claim 1, wherein the controller is further configured to control the pump and the fluid-selection valve to transport the oxygenated calibration fluid out of the oxygenation tubing into the sensor path while introducing fresh deoxygenated fluid into the oxygenation tubing to be oxygenated.
6. An automatic method of calibrating a sensor located in a flow-through sensor path of a detecting unit of an in-vitro diagnostic (IVD) analyzer involving a reaction with oxygen in a sample in order to determine a sample parameter and requiring at least one oxygenated calibration fluid with a certain level of oxygenation for calibration, the method comprising controlling by a controller a pump and a fluid-selection valve, including transporting deoxygenated calibration fluid from a fluid-supply unit into an oxygenation tubing having two ends fluidically connected to the fluid-selection valve as a loop, the oxygenation tubing comprising oxygen-permeable walls, the fluid-selection valve comprising one or more fluid input ports for selecting at least one fluid at a time, and a common outlet port fluidically connected or connectable via a fluidic line to the sensor path, waiting a predetermined time required for oxygenation of the deoxygenated calibration fluid via oxygen uptake from ambient air through the tubing walls until the required level of oxygenation is obtained, thereby obtaining an oxygenated calibration fluid, and transporting the thereby obtained oxygenated calibration fluid into the sensor path and calibrating the at least one sensor.
7. The method according to claim 6, wherein the at least one sensor is a metabolite sensor including at least one of a glucose sensor and a lactate sensor.
8. The method according to claim 6, further comprising transporting different deoxygenated calibration fluids to be oxygenated into respective oxygenation tubings
9. The method according to claim 6, further comprising controlling the pump and the fluid-selection valve to transport any other fluid from the fluid-supply unit into the sensor path while the at least one oxygenation tubing is fluidically isolated and the deoxygenated calibration fluid is being oxygenated.
10. The method according to claim 6, further comprising controlling the pump and the fluid-selection valve to transport the oxygenated calibration fluid out of the oxygenation tubing into the sensor path while introducing fresh deoxygenated fluid into the oxygenation tubing to be oxygenated.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0038] FIG. 1A shows schematically an in-vitro diagnostic analyzer comprising a flow-through sensor path and a first step of an automated method of calibrating a sensor located in the flow-through sensor path.
[0039] FIG. 1B shows schematically the same in-vitro diagnostic analyzer of FIG. 1A and a second step of the same automated method.
[0040] FIG. 1C shows schematically the same in-vitro diagnostic analyzer of FIG. 1A-1B and a third step of the same automated method.
[0041] FIG. 1D shows schematically the same in-vitro diagnostic analyzer of FIG. 1A-1C and a fourth step of the same automated method.
[0042] FIG. 1E shows schematically the same in-vitro diagnostic analyzer of FIG. 1A-1D and a fifth step of the same automated method.
[0043] FIG. 2 shows schematically the same in-vitro diagnostic analyzer of FIG. 1A-1E and a step of transporting a sample for analysis after sensor calibration.
[0044] FIG. 3 shows schematically the same in-vitro diagnostic analyzer of FIG. 1A-1E and a variant of the step shown in FIG. 1E.
[0045] FIG. 4 shows more in detail and in cross section parts of a fluid-selection valve integrated into a manifold and an oxygenation tubing, during the step shown in FIG. 1A.
[0046] FIG. 5 shows similar details as in FIG. 4 during the step shown in FIG. 3.
[0047] FIG. 6 looks like FIG. 4 but is in connection to the step shown in FIG. 1D.
[0048] FIG. 7 shows the progressive level of oxygenation achieved with different predetermined times for oxygen uptake in the oxygenation tubing.
[0049] Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements whereas other elements may have been left out or represented in a reduced number in order to enhance clarity and improve understanding of the aspects of the present disclosure.
DETAILED DESCRIPTION
[0050] FIG. 1A to FIG. 1E taken together show schematically an example of in-vitro diagnostic analyzer 200 comprising a flow-through sensor path 211 according to the present disclosure as well as an automated method of calibrating a sensor 212 located in the flow-through sensor path 211. In particular, the in-vitro diagnostic analyzer 200 comprises a detecting unit 210 comprising a flow-through sensor path 211, the flow-through sensor path 211 comprising at least one sensor 212 involving a reaction with oxygen in a sample in order to determine a sample parameter and requiring at least one oxygenated calibration fluid with a certain level of oxygenation for calibration. According to an embodiment, the at least one sensor 212 is a metabolite sensor including at least one of a glucose sensor and a lactate sensor.
[0051] The IVD analyzer 200 further comprises a fluid-supply unit 220 comprising at least one deoxygenated calibration fluid 221, 222 among other fluids 223, a fluid-selection valve 230 for selecting at least one fluid 221, 222, 223 at a time, and a fluidic line 213 comprised between the valve 230 and the sensor path 211. The IVD analyzer 200 further comprises a sample input interface 100, comprising a sample input port 10 comprising an outer input-port side 11 configured for plugging-in an open end of a sample container 1 and an inner input-port side 12. The sample container 1 is in this example is a capillary-like sample container. The sample input interface 100 further comprises an aspiration needle 30 comprising an upstream end 31 and a downstream end 32. The downstream end 32 of the aspiration needle 30 is fluidically connected to the sensor path 211 via the fluidic line 213 whereas the upstream end 31 is configured to alternately couple to the inner input-port side 12 in order to aspirate a sample from a sample container 1 plugged in the outer input-port side 11 and to a fluid supply unit port 10 fluidically connected to a common outlet port 231 of the fluid-selection valve 230 via a further conduit 214. The fluidic line 213 may be however directly connected to the outlet port 231 of the fluid-selection valve 230, whereas samples may be introduced via a different fluidic line separately connected to the fluid-selection valve 230, for example. The fluid-selection valve comprises also an air port 232. The IVD analyzer 200 further comprises in this example two oxygenation tubings 215, 216 each having two ends connected to the fluid-selection valve 230 as a loop, the oxygenation tubings comprising oxygen-permeable walls.
[0052] The IVD analyzer 200 further comprises a pump 240, such as a peristaltic pump, located downstream of the sensor path 211 and also a waste container 224, located in the fluid-supply unit 220, where fluids circulated through the fluidic line 213 and sensor path 211 may be disposed of.
[0053] The IVD analyzer 200 further comprises a controller 250 configured to automatically execute any of the herein disclosed method steps.
[0054] In particular, FIG. 1A shows schematically, the position of the fluid being indicated by bold lines, a first step of the automated method of calibrating the at least one sensor 212 located in the flow-through sensor path 211 of a detecting unit 210 of an in-vitro diagnostic (IVD) analyzer 200 involving a reaction with oxygen in a sample in order to determine a sample parameter and requiring at least one oxygenated calibration fluid with a certain level of oxygenation for calibration. The method comprises controlling by the controller 250 the pump 240 and the fluid-selection valve 230, including transporting a first deoxygenated calibration fluid 221 from the fluid-supply unit 220 into a first oxygenation tubing 215.
[0055] The method continues, as shown in FIG. 1B, by waiting a predetermined time required for oxygenation of the deoxygenated calibration fluid 221via oxygen uptake from ambient air through the walls of the oxygenation tubing 215 until the required level of oxygenation is obtained, thereby obtaining a first oxygenated calibration fluid. The method further comprises transporting a second deoxygenated calibration fluid 222 to be oxygenated into a second respective oxygenation tubing 216, while the first oxygenation tubing 215 is fluidically isolated and the first deoxygenated calibration fluid 221 is being oxygenated.
[0056] As shown in FIG. 1C, the method further comprises controlling the pump 240 and the fluid-selection valve 230 to transport any other fluid 223 from the fluid-supply unit 220 into the sensor path 211 while the oxygenation tubings 215, 216 are fluidically isolated and the calibration fluids are being oxygenated.
[0057] As shown in FIG. 1D and FIG. 1E, the method further comprises transporting the obtained first oxygenated calibration fluid 221 from the oxygenation tubing 215 into the sensor path 211 and calibrating the at least one sensor 212, while the second deoxygenated calibration fluid 222 continues the oxygenation step. Once the oxygenation step for the second deoxygenated calibration fluid 222 is completed, the method comprises transporting also the second obtained second oxygenated calibration fluid 222 from the second oxygenation tubing 216 into the sensor path 211 and calibrating the at least one sensor 212 (not shown).
[0058] FIG. 2 shows schematically the same in-vitro diagnostic analyzer 200 of FIG. 1A-1E and a step of transporting a sample 2 from the sample container 1 plugged in the outer input-port side 11 of the sample input port 10, while the upstream end 31 of the aspiration needle 30 is coupled to the inner input-port side 12 of the sample input port 10, for analysis of the sample 2 by the sensor 212 after calibration according to the method of FIG. 1A-1E. After calibration and before transporting a sample, an intermediate cleaning step with another fluid may take place (not shown). The controller 250 is in this case also configured to control the aspiration needle 30 to alternately couple to the inner input-port side 12 in order to aspirate a sample from a sample container 1 plugged in the outer input-port side 11 and to the fluid-supply unit port 40 for performing the other steps. The step of transporting a sample and analyzing the sample may also be executed while the calibration fluid is in the oxygenation tubing and the oxygenation step is ongoing.
[0059] In general, the method of FIG. 1A-1E enables tonometry of deoxygenated calibration fluids without unnecessarily extending the calibration time and/or enables parallel steps in the meantime, by preventing blocking the use of the fluidic system and of the pump while waiting for oxygenation.
[0060] FIG. 3 shows schematically the same in-vitro diagnostic analyzer of FIG. 1A-1E and a variant of the step shown in FIG. 1E. This variant of the method comprises controlling the pump 240 and the fluid-selection valve 230 to transport the oxygenated calibration fluid 221 out of the oxygenation tubing 215 into the sensor path 211 while introducing fresh deoxygenated fluid 221 into the oxygenation tubing 215 to be oxygenated.
[0061] FIG. 4 shows more in detail, a perspective and cross-sectional view of parts of an embodiment comprising a fluid selection valve 230 integrated into a manifold 260, of an oxygenation tubing 215 connected to the manifold 260 as a loop and of a fluid reservoir 225 with an on/off valve 226 also connected to the manifold 260. In particular, the manifold 260 comprises a channel 261 and a respective input port 262, 263 for each fluid reservoir 225 (only one fluid reservoir shown for simplicity). The input ports 262, 263 all lead to the same and common channel 261 and to a common fluid input port 233 of the fluid-selection valve 230. Each fluid reservoir 225 comprises an individual on/off valve 226 by which the fluid reservoir 225 is connected to the respective input port 262 of the manifold 260, in order to allow selected fluids 221 from selected fluid reservoirs 225 to flow into the common channel 261 and to the fluid-selection valve 230. FIG. 4 shows schematically, by means of arrows, the same step shown also in FIG. 1A comprising transporting a deoxygenated calibration fluid 221 from a fluid reservoir 225 into an oxygenation tubing 215 (only one oxygenation tubing shown for simplicity). In particular, the fluid-selection valve 230 is in a switch position, obtained by rotation of an actuation member 234, that enables the calibration fluid to flow via the fluid input port 233 into the fluid selection valve 230 and via the fluid-selection valve 230 through the oxygenation tubing 215 and again via the fluid-selection valve 230 out via the outlet port 231. The on/off valve 226 is in the on status while all other on/off valves (not shown) of the other fluid reservoirs (not shown) are in the off status.
[0062] FIG. 5 shows a front and partly cross-sectional view with details and parts similar to that shown in FIG. 4. In particular, FIG. 5 additionally shows a second fluid reservoir 227 containing fluid 223, in this example different from a calibration fluid, connected to the input port 263 of the manifold 260 via the on/off valve 228. The on/off valve 228 is in the on status while the on/off valve 226 and all other on/off valves (not shown) of other fluid reservoirs (not shown) are in the off status. The fluid-selection valve 230 is in a switch position, obtained by rotation of the actuation member 234, that enables the different fluid 223 to flow via the manifold channel 261 and the fluid input port 233 into the fluid selection valve 230 and via the fluid-selection valve 230 to the outlet port 231 leading to the sensor path (not shown in FIG. 5), while the oxygenation tubing 215, with the calibration fluid inside being oxygenated, is fluidically isolated. The oxygenation tubing 215 is made of a material permeable to oxygen from ambient air, e.g. made of silicone. Thus, FIG. 5 also shows, schematically by means of arrows, the same step shown also in FIG. 1C of transporting any other fluid 223 from the fluid-supply unit into the sensor path while the oxygenation tubing 215 is fluidically isolated and the deoxygenated calibration fluid is being oxygenated.
[0063] FIG. 6 is nearly identical to FIG. 1 but schematically showing, also by means of arrows, the same step shown in FIG. 3, comprising transporting the oxygenated calibration fluid 221 out of the oxygenation tubing 215 into the sensor path (not shown in FIG. 6) via the outlet port 231 while introducing fresh deoxygenated fluid 221 into the oxygenation tubing 215 to be oxygenated.
[0064] With continued reference to FIG. 4-6 the controller (not shown) is configured to control also the on/off valves 226, 228 besides the fluid-selection valve 230 and the pump 240 such as to select a fluid at a time.
[0065] FIG. 7 is a diagram showing the progressive level of oxygenation of a calibration fluid achieved over time in an oxygenation tubing as used in the above examples, by measuring the partial pressure of oxygen pO.sub.2 in mmHg at different time points, e.g. by repeating the process with progressively longer waiting times and measuring the respective pO.sub.2 of the partially oxygenated calibration fluid in the sensor path. It can be seen that in order to obtain a sufficient level oxygenation, that is typically about 80-90% of the partial pressure of oxygen in ambient air, that is about 110-170 mmHg, depending e.g. on altitude of it may be required to wait several minutes, beyond the time shown in the diagram. Although not explicitly illustrated in the above examples, it is clear that several other steps may be executed during this time, thanks to the fact that fluidic system and the pump remain available for use during this time.
[0066] Modifications and variations of the disclosed aspects are also certainly possible in light of the above description. It is therefore to be understood, that within the scope of the appended claims, the invention may be practiced otherwise than as specifically devised in the above examples.
[0067] Particularly, it is to be understood that at least some of the drawings or parts are only schematic and provided as way of example only. Also the relationship between elements may be other than the one shown, whereas parts not relevant for the purpose of this disclosure have been omitted.
[0068] Also, reference throughout the preceding specification to one example or an example, means that a particular feature, structure or characteristic described in connection with the aspect or example is included in at least one aspect. Thus, appearances of the phrases one example or an example, in various places throughout this specification are not necessarily all referring to the same example.
[0069] Furthermore, the particular features, structures, or characteristics may be combined in any suitable combinations and/or sub-combinations in one or more aspects or examples.
