Platelet concentrate control

Abstract

An apparatus (1) for determining the quality of concentrated platelets (15) in a concentrated platelet (PC) bag (10) includes a movable bag holder (2) for carrying the PC bag (10), an optical system (20) having light sources (21, 24) for directing light (22) into the concentrated platelets (15) in the PC bag (10) during a measurement interval, and a detector system (30) having light detectors (31, 32) configured to detect light (23) from the concentrated platelets 15 during the measurement interval and generate a real-time detection signal. The apparatus (1) also includes a controller (40) configured to determine platelet swirl based on the real-time detection signal and to determine a quality parameter of the concentrated platelets (15) in the PC bag (10) based on the platelet swirl.

Description

Technical Field

[0001] The present invention relates generally to platelet concentrate control, and in particular to an apparatus and method for determining the quality of platelet concentrates. Background Art

[0002] Platelet concentrates (PC), also known in the art as concentrated thrombocytes, are used for platelet transfusions to prevent or treat bleeding in patients with thrombocytopenia and / or platelet dysfunction. Typical patients who receive such platelet transfusions are those being treated with chemotherapy.

[0003] Platelet concentrates can be produced from whole blood or by apheresis and have a shelf life of five to seven days. Platelet storage conditions differ significantly from those of other blood components, such as red blood cells and plasma, in terms of temperature. Currently, platelet concentrates are stored in oxygen-permeable bags at a temperature of 20 to 22°C in dedicated cabinets with temperature control and removable shelves for agitating the platelets. This agitation serves to prevent platelet aggregation and optimizes oxygenation of the platelets in the bag.

[0004] The production of blood components places stringent demands on quality control and grading. Currently, the quality of platelet concentrates is determined through subjective visual inspection of so-called platelet swirl. Platelet swirl is the term for an optical phenomenon that occurs when viable platelets in a bag reflect light in a characteristic manner. Platelets are flat, round, and colorless, yet possess a unique ability to reflect light. As platelets age and eventually die, they become rounder and their light-reflecting properties diminish. Consequently, the swirl effect decreases as aged platelets die.

[0005] Currently, there is no objective way to measure platelet swirl in absolute terms. For clarity of comparison, platelet swirl test results are recorded as positive swirl or extensive swirl, moderate swirl or intermediate swirl, and absent swirl or negative swirl. Therefore, quality control of platelet concentrates remains a subjective assessment by blood bank staff who manufacture and supply platelet concentrate products.

[0006] WO 90 / 14588 discloses an apparatus for continuous quality control of platelet concentrates. A light source is arranged to transilluminate a bag containing the platelet concentrate, and a photodiode is arranged to detect light that has passed through the bag containing the platelet concentrate. The detection signal is used to monitor any changes in turbidity or transparency, which is said to reflect the quantity and quality of the platelets in the bag.

[0007] US Pat. No. 6,288,778 discloses an apparatus for processing blood in a bag. The apparatus includes a plurality of circular discs arranged one above the other and rotatable about a common central axis. Each disc is inclined at an angle to the central axis. A light source is disposed below each of the discs, and a photosensitive member is disposed above each of the discs. Light emitted by the light source passes through an aperture in the disc and through a bag to be detected by the photosensitive member. The detected light can be used to measure the glare of thrombocytes in the blood in the bag retained on the discs.

[0008] There remains a need for a technique for determining the quality of platelet concentrates, and particularly for such a technique that can detect contaminants in platelet concentrates. Summary of the Invention

[0009] The overall goal is to determine the quality of platelet concentrates.

[0010] This object and others are met by the embodiments as disclosed herein.

[0011] The invention is defined in the independent claims. Further embodiments of the invention are defined in the dependent claims.

[0012] Embodiments of the present invention relate to an apparatus for determining the quality of platelet concentrate in a platelet concentrate (PC) bag. The apparatus includes a movable bag holder configured to carry the PC bag and agitate the platelets in the PC bag. The apparatus also includes an optical system comprising at least one light source configured to direct light into the platelet concentrate in the PC bag carried by the movable bag holder during a measurement interval. The apparatus also includes a detector system comprising at least one light detector configured to detect light from the platelet concentrate in the PC bag during the measurement interval and generate a real-time detection signal. The apparatus further includes a controller connected to the detector system and configured to determine platelet swirl of the platelet concentrate in the PC bag based on the real-time detection signal and to determine a quality parameter of the platelet concentrate in the PC bag based on the platelet swirl.

[0013] Another embodiment of the present invention relates to a method for determining the quality of platelet concentrate in a PC bag. The method includes directing light into the platelet concentrate in the PC bag carried by a removable bag holder during a measurement interval. The removable bag holder is configured to carry the PC bag and agitate the platelets in the PC bag. The method also includes detecting light from the platelet concentrate in the PC bag during the measurement interval. The method also includes generating a real-time detection signal based on the detected light and determining a platelet swirl of the platelet concentrate in the PC bag based on the real-time detection signal. The method further includes determining a quality parameter of the platelet concentrate in the PC bag based on the platelet swirl.

[0014] The present invention enables accurate monitoring of the quality of platelet concentrates even in the presence of contaminants in the PC bag.In addition to monitoring the quality of platelets, embodiments of the present invention can also be used to detect any contaminants in the platelet concentrates. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The embodiments, together with further objects and advantages thereof, may best be understood by referring to the following description taken in conjunction with the accompanying drawings, in which:

[0016] Figure 1A and Figure 1B An apparatus for determining the quality of a platelet concentrate according to one embodiment is presented;

[0017] Figure 2A and Figure 2B An apparatus for determining the quality of a platelet concentrate according to another embodiment is presented;

[0018] Figure 3 An apparatus for determining the quality of a platelet concentrate according to yet another embodiment is presented;

[0019] Figure 4 An apparatus for determining the quality of a platelet concentrate according to yet another embodiment is presented;

[0020] Figure 5 An apparatus for determining the quality of a platelet concentrate according to yet another embodiment is presented;

[0021] Figure 6A and Figure 6B An apparatus for determining the quality of a platelet concentrate according to another embodiment is presented;

[0022] 7A to 7C An apparatus for determining the quality of a platelet concentrate according to another embodiment is presented;

[0023] Implementation Method Figure 8 An apparatus for determining the quality of a platelet concentrate according to yet another embodiment is presented;

[0024] Figure 9 is a graph showing real-time reflectance signals of spun platelets determined for platelet concentrates 2 and 12 days from production. Amplitudes and averages are shown;

[0025] Figure 10A and Figure 10B Figure 2 shows the reflectance signals determined for platelet concentrates lacking microbial contaminants expressed as mean values (RM, TM) and amplitudes (RS, TS) over time (approximately 8 days). Figure 10A ) and transmission signal ( Figure 10B )

[0026] Figure 11A and Figure 11B Figure 2 shows the reflectance signals determined for platelet concentrates with Staphylococcus epidermidis contamination expressed as mean values (RM, TM) over time (approximately 8 days) and amplitudes (RS, TS) over time. Figure 11A ) and transmission signal ( Figure 11B )

[0027] Figure 12 is a graph showing the reflectance signal (Swirl) and the average value of the transmission signal (Transmission Mean) of uncontaminated platelet concentrate (unspiked) and contaminated platelet concentrate (spiked);

[0028] Figure 13A and Figure 13B is demonstrated for uncontaminated platelet concentration ( Figure 13A ) and the concentration of contaminated platelets ( Figure 13B ) a graph of the determined reflection signal (RS) and the transmission signal average (TM);

[0029] Figure 14A and Figure 14B The concentration of uncontaminated platelets ( Figure 14A ) and the concentration of contaminated platelets ( Figure 14B ) compared with visual assessment of the reflected signal (RS) and swirl flow (SW) and aggregation at 16 μM collagen (F1), at 8 μM collagen (F2), at 0.5 mg / ml arachidonic acid (ARA) (F5), and at 20 μM thrombin receptor activating peptide (TRAP) (F6);

[0030] Implementation Method Figure 15 An apparatus for determining the quality of a platelet concentrate according to one embodiment is presented;

[0031] Figure 16 An apparatus for determining the quality of a platelet concentrate according to another embodiment is presented;

[0032] Figure 17 is a flow chart illustrating a method for determining the quality of platelet concentrates in PC bags,

[0033] Figure 18 is a diagram showing a method according to an embodiment of the present invention. Figure 17 A flowchart of additional optional steps of the method shown; and

[0034] Implementation Method Figure 19 It shows that according to another embodiment Figure 17 A flow chart of additional optional steps of the method shown. DETAILED DESCRIPTION

[0035] Throughout the drawings, the same reference numerals are used for similar or corresponding elements.

[0036] The present invention relates generally to platelet concentrate control, and in particular to an apparatus and method for determining the quality of platelet concentrates.

[0037] Prior art devices proposed for continuous quality control of platelet concentrates use average transmitted light, i.e., light that has passed through the platelet concentrate (PC), to monitor any changes in turbidity or transparency, and use this turbidity or transparency to monitor the quantity and quality of platelets in the PC bag.

[0038] However, experimental data presented herein indicate that this average transmission signal can be problematic in the presence of contaminants in the platelet concentration, such as contamination by bacteria or other microorganisms. Such bacterial contamination is relatively more common in platelets than in other blood components because they are stored at warmer temperatures.

[0039] When measuring average light transmission, any degradation in the quality of the platelets in the PC bag will be masked by contamination because microbial growth causes a change in transmission that is opposite to the change in average transmission caused by platelet degradation. Therefore, if there is microbial contamination in the monitored PC bag, an operator or user monitoring the average transmission signal over time can assume that the quality of the platelet concentration is good, even though a large portion of the platelets have actually degraded and died.

[0040] The present invention is based on the discovery that platelet swirl, as determined based on a real-time detection signal, is a more suitable tool for monitoring the quality of a platelet concentrate than an average transmission signal and other signals indicative of turbidity or transparency. Any change in the platelet quality of the platelet concentrate is accurately represented by the platelet swirl, as determined based on the real-time detection signal, even if the platelet concentrate is contaminated with microorganisms.

[0041] Embodiments of the present invention relate to an apparatus for determining the quality of platelet concentrate in a platelet concentrate (PC) bag. The apparatus includes a movable bag holder configured to carry the PC bag and agitate the platelets in the PC bag. The apparatus also includes an optical system comprising at least one light source configured to direct light into the platelet concentrate in the PC bag carried by the movable bag holder during a measurement interval. The apparatus also includes a detector system comprising at least one light detector configured to detect light from the platelet concentrate in the PC bag during the measurement interval and generate a real-time detection signal. The apparatus further includes a controller connected to the detector system and configured to determine platelet swirl of the platelet concentrate in the PC bag based on the real-time detection signal and to determine a quality parameter of the platelet concentrate in the PC bag based on the platelet swirl.

[0042] The present information uses a real-time detection signal reflecting the detection light during a time period corresponding to the measurement interval to determine platelet swirl. This real-time detection signal accurately reflects the swirl effect caused by the platelets in the platelet concentrate in the PC bag. Figure 9 The real-time reflectivity signal is shown as measured for platelet concentrate 2 days after filling the PC bag with the platelet concentrate and again 12 days later. After 2 days, most platelets are viable, causing a significant swirl effect, as can be seen as a large variability or difference in the real-time reflectivity signal, sometimes also referred to as the time-dependent signal intensity of the real-time reflectivity signal. However, after 12 days, the viability of the platelets is much lower, thus not producing any significant swirl effect. Therefore, the variability of the real-time reflectivity signal is significantly lower.

[0043] Therefore, in an embodiment, the controller of the device is configured to determine the platelet swirl of the concentrated platelets in the PC bag based on the variability or difference in the real-time detection signal and determine the quality parameter of the concentrated platelets in the PC bag based on the platelet swirl.

[0044] The variability or variance of the real-time detection signal may be defined according to various embodiments. In an embodiment, the real-time detection signal comprises a plurality of signal samples. The number of such signal samples depends on the sampling frequency of the at least one light detector and the duration of the measurement interval. Each signal sample has a corresponding value, also denoted herein as sample value. In an example, the variability or variance may be defined as a preferably time-dependent variation of the difference or distance between the signal value of a signal sample and the average value of the real-time detection signal (i.e., the average value of the signal samples). As in Figure 9 As shown in the upper part of , there is a large variation in the sample values relative to the mean, that is, there is a large difference or distance between the signal values and the mean of the signal values, while Figure 9In the lower part of , there is a correspondingly much lower variation in the signal value relative to the mean.

[0045] Thus, in an embodiment, the real-time detection signal comprises a plurality of signal samples having corresponding sample values. The controller is then configured to calculate an average of the sample values of the signal samples and determine the platelet swirl based on the calculated average and the sample values of the signal samples.

[0046] For example, assume that the real-time detection signal includes N signal samples in the measurement interval and s i represents the sample value at sample number i (i=1…N), then the sample value and thus the average value of the real-time detection signal can be calculated by the controller as

[0047] In this embodiment, the controller is therefore configured to calculate the value of the sample based on the average of the sample values and the sample values of the signal samples (ie based on a certain function f( ) ) to determine platelet vortex.

[0048] In an embodiment, the controller is configured to calculate a difference between a sample value of the signal sample and a calculated average value for each signal sample of the real-time detection signal. In this embodiment, the controller is further configured to determine the platelet swirl based on the calculated difference.

[0049] In this embodiment, the controller calculates the sample value s of the signal sample i With the calculated average The difference or distance Δs between i , and then based on these differences (such as g(Δs i )) to determine the platelet swirl. Such a difference or distance can be calculated, for example, as (For those sample values ) and is calculated as (For those sample values ), or the controller can calculate the absolute or squared difference, e.g. or

[0050] In an embodiment, the controller is configured to determine the platelet swirl based on the sum of the calculated differences. Therefore, the currently preferred examples of determining platelet swirl include and

[0051] and Figure 9 The real-time detection signal in the lower part is compared to Figure 9The real-time detection signal in the upper part will result in a relatively larger value of the calculated sum of the differences.

[0052] The controller may alternatively calculate other parameters representing the variability of the real-time detection signal, preferably relative to the average value of the real-time detection signal. For example, the controller may calculate the area under the curve, such as relative to the average value of the real-time detection signal. Other parameters include the difference or distance Δs for those signal samples whose sample values are greater than the average value of the real-time detection signal. i The sum is performed to obtain a first sum, and the difference or distance Δs for those signal samples whose sample values are less than the average value of the real-time detection signal i The controller may then calculate the sum of the two sums, calculate the difference between the absolute value of the first sum and the absolute value of the second sum, calculate the sum of the absolute value of the first sum and the absolute value of the second sum, or calculate the quotient of the first sum and the second sum as a parameter representing platelet swirl.

[0053] In a preferred embodiment, the real-time detection signal is a real-time reflectivity signal, i.e., a signal representing light reflected from the platelet concentrate during a measurement interval. In this embodiment, the detector system includes a light detector configured to detect reflected light from the platelet concentrate in the PC bag during the measurement interval and to generate a real-time reflectivity signal representing light reflected from the platelet concentrate during the measurement interval. In this embodiment, the controller is configured to determine platelet swirl based on the real-time reflectivity signal.

[0054] The apparatus of the present invention will now be described with reference to various embodiments shown in the accompanying drawings.

[0055] Figure 1A and Figure 1B An embodiment of an apparatus 1 for determining the quality of platelet concentrate 15 in a PC bag 10 is shown. In this embodiment, an optical system 20 includes a light source 21 arranged to direct light 22 into the platelet concentrate 15 in the PC bag 10 at an incident angle α selected within a range of 5° to 85° during a measurement interval. In this embodiment, a detector system 30 includes a light detector 31 configured to detect reflected light 23 from the platelet concentrate 15 in the PC bag 10 during the measurement interval. The light detector 31 is further configured to generate a real-time reflectivity signal representing the light reflected from the platelet concentrate 15 during the measurement interval. This reflectivity signal is processed by a controller 40 connected to the detector system 30. Thus, the controller 40 determines the platelet swirl of the platelet concentrate 15 in the PC bag 10 based on the real-time reflectivity signal and determines a quality parameter of the platelet concentrate 15 in the PC bag 10 based on the platelet swirl.

[0056] exist Figure 1A and Figure 1B In the illustrated embodiment, the optical system 20 and the detector system 30 each include a light source 21 and a light detector 31. Light source 21 and light detector 31 are arranged on the same side relative to the PC bag 10 and the removable bag holder. Furthermore, light source 21 is arranged on this side to direct light 22 at an angle of incidence α onto the platelet concentrates 15 in the PC bag 10. This angle of incidence is selected so that light detector 31 can detect reflected light 23 from the platelet concentrates 15 in the PC bag 10. Thus, this angle of incidence α is selected within the range of 5° to 85°. In a preferred embodiment, the angle of incidence α is selected within the range of 15° to 85°, and more preferably within the range of 25° to 85°. In a specific embodiment, the angle of incidence α is at least 25°, preferably at least 30°, more preferably at least 35°, such as at least 40° or at least 45°, but does not exceed 85°, preferably does not exceed 80°, and more preferably does not exceed 75°. Therefore, the preferred range of the incident angle α is from 45° to 75°.

[0057] Experimental data as provided herein indicate that the real-time reflectivity signal is a good representation of platelet swirl caused by light diffraction due to the alignment of normally flat, round platelets. These flat rounds will be aligned by the diffracted light, resulting in a cloud-like or swirl-like appearance that is well captured by monitoring the real-time reflectivity signal, and in particular the reflectivity signal amplitude. Figure 9 The real-time reflectivity signal measured 2 days and 12 days after the platelet concentrate in the PC bag was produced is shown. As shown, after 2 days, when the quality of the platelets in the platelet concentrate was good, the reflectivity signal variability or difference was significantly higher, while after 12 days, when many platelets had died, the reflectivity signal variability or difference was much smaller. Therefore, the reflectivity signal variability can be advantageously used to determine the quality parameter. Compared with the degenerated platelets (low quality or poor quality), as shown after 12 days, this reflectivity signal variability is higher for the viable platelets (high quality or good quality), as shown after 2 days.

[0058] In an embodiment, at least one light source 21 is configured to direct light 22 at an incident angle α into the platelet concentrate 15 in the PC bag 10 over a measurement interval of at least 0.5 seconds, preferably at least 1 second. In an embodiment, the measurement interval is no longer than 40 seconds, preferably no longer than 30 seconds, and more preferably no longer than 20 seconds. Therefore, in an embodiment, the measurement interval is selected within a range of from 0.5 seconds to 40 seconds, preferably within a range of from 1 second to 30 seconds, and more preferably within a range of from 1 second to 20 seconds, such as 1 second, 2 seconds, 3 seconds, 4 seconds, 5 seconds, 6 seconds, 7 seconds, 8 seconds, 9 seconds, 10 seconds, 11 seconds, 12 seconds, 13 seconds, 14 seconds, 15 seconds, 16 seconds, 17 seconds, 18 seconds, 19 seconds, or 20 seconds, preferably from 1 second to 10 seconds or from 1 second to 5 seconds. In this embodiment, at least one detector 31 is configured to detect reflected light 23 from the platelet concentrate 15 in the PC bag 10 during a measurement interval and generate a real-time reflectivity signal representing the light reflected from the platelet concentrate 15 during the measurement interval. The controller 40 is then configured to determine the platelet swirl of the platelet concentrate 15 in the PC bag 10 based on the real-time reflectivity signal.

[0059] As mentioned above, in an embodiment, the controller 40 may determine an average reflectivity signal based on the real-time reflectivity signal. In such an embodiment, the controller 40 is configured to determine a quality parameter based on the average reflectivity signal and the real-time reflectivity signal. For example, the controller 40 may be configured to determine, for each signal sample of the real-time reflectivity signal, a difference between the sample value and the average reflectivity signal, and then determine platelet swirl based on the calculated difference.

[0060] In an embodiment, a controller 40 is connected to the optical system 20 and the detector system 20 and is configured to control the light source 21 of the optical system 20 to direct light 22 at an incident angle α onto the platelet concentrates 15 in the PC bag 10 carried by the bag holder 2. The controller 40 is also configured to control the light detector 31 of the detector system 30 to detect reflected light 31 from the platelet concentrates 15 in the PC bag 10 and generate a real-time reflectance signal. Thus, in this embodiment, light measurements are performed at preferably scheduled measurement intervals. At these measurement intervals, the controller 40 activates the light source 21 to direct light 22 into the platelet concentrates 15 and preferably activates the light detector 31 to detect reflected light 31 from the platelet concentrates 15. Therefore, the light source 21 and light detector 31 need only be active during measurement intervals and can be in an inactive or low-power mode at other times. Switching between the inactive or low-power mode and the active or high-power mode is then performed by the controller 40.

[0061] In an embodiment, for a selected value of X (such as 1 to 7, preferably 1 to 5 and more preferably 1 to 3), at least one measurement is performed every X days. Thus, in an embodiment, multiple measurements are performed a week, such as at least twice a week, preferably at least three times a week. In an embodiment, the measurements are performed at least once a day or at least multiple times a day. In this case, for a selected value of Y (such as 1 to 24, for example 1 to 12 or 1 to 4), a measurement may be performed every Y hours. Manual visual inspection of concentrated platelets is typically performed once a day. Thus, in an embodiment, the measurements performed with the apparatus 1 of the present invention are also performed once a day. However, it may be advantageous to perform more than one measurement a day, such as to filter out noise or artifacts. According to the present invention, more or fewer continuous measurements may actually be performed, in particular for providing, for example, Figure 15 An apparatus 1 for the horizontal movement of a PC bag 10 is shown and is generally referred to as a Helmer style.

[0062] Figure 1A and Figure 1B The device 1 shown is particularly suitable for real-time reflectivity or reflection signal measurement. Figure 2A and Figure 2B Another embodiment of the device 1 is shown that is also suitable for real-time reflectivity signal measurement. In this embodiment, the optical system 20 further includes a light source 21, and the detector system 30 includes a light detector 31. However, in this embodiment, the light source 21 is arranged at a first side relative to the movable bag holder, while the light detector 31 is arranged at a second, opposite side relative to the movable bag holder.

[0063] As schematically shown in the figure, the light detector 31 is preferably arranged relative to the light source 21 and the movable bag holder so as to be able to detect the reflected light 23 from the concentrated platelet 15 in the PC bag 10 during the measurement interval. This means that the light detector 31 is preferably displaced relative to the light path corresponding to the incident light 22 and the transmitted light (reflected by the light source 21) that passes directly through the concentrated platelet 15 in the PC bag 10. Figure 2B ). Thus, the light detector 31 is preferably configured to detect light 23 that leaves the PC bag 10 at a non-zero angle relative to the light path described above.

[0064] and Figure 1A and Figure 1B Compared to the embodiment shown, Figure 2A and Figure 2B The illustrated embodiment detects reflected light in another direction relative to the platelet concentrate 15 and PC bag 10 .

[0065] Figure 3Yet another embodiment of an apparatus 1 configured to generate a real-time reflectance signal is shown. In this embodiment, the optical system 20 includes a light source 21, but the detector system 30 includes a first light detector 31 and a second light detector 32. The light source 21 and light detector 31 are arranged on a first side relative to the movable bag holder, while the second light detector 32 is arranged on a second, opposite side relative to the movable bag holder. The first light detector 31 and the second light detector 32 are then configured to detect reflected light from the platelet concentrate 15 in the PC bag 10 during a measurement interval and generate corresponding real-time reflectance signals representing the light reflected from the platelet concentrate 10 during the measurement interval. The two light detectors 31, 32 are thus arranged to detect reflected light from different angles or directions relative to the platelet concentrate 15 in the PC bag 10.

[0066] In this embodiment, the controller 40 is configured to determine platelet swirl based on a first real-time reflectivity signal from the first light detector 31 and a second real-time reflectivity signal from the second light detector 32. For example, the controller 40 can process each of the first real-time reflectivity signal and the second reflectivity signal separately, as discussed above, to calculate, for example, a first sum of calculated differences between sample values in the first real-time reflectivity signal and an average value of the first real-time reflectivity signal and a second sum of calculated differences between sample values in the second real-time reflectivity signal and an average value of the second real-time reflectivity signal. The controller 40 can then determine platelet swirl based on the first sum and the second sum. For example, the controller 40 can determine platelet swirl based on the average of the first sum and the second sum, or the sum of the first sum and the second sum.

[0067] In another embodiment, the controller 40 may instead determine an average real-time reflectivity signal based on the first real-time reflectivity signal and the second real-time reflectivity signal, and then determine platelet swirl based on the average real-time reflectivity signal, such as discussed above.

[0068] Figure 4 1 is a diagram of an apparatus 1 capable of performing real-time reflectance measurement according to another embodiment. In this embodiment, an optical system 20 includes a light source 21 arranged at a first side relative to the removable bag holder and the PC bag 10, and a detector system 30 includes a first light detector 31 arranged at the first side relative to the removable bag holder and the PC bag 10 and a second detector 32 arranged at a second, opposite side relative to the removable bag holder and the PC bag 10.

[0069] In such Figure 4 In the embodiment shown, the PC bag 10 is preferably arranged in a removable bag holder ( Figure 41 (not shown) so as to be angled at an angle α relative to the horizontal axis. This also means that some light will pass directly through the platelet concentrates 15 in the angled PC bag 10, and some light will be reflected from the platelet concentrates 15 in the angled PC bag 10 and detected by the first light detector 31 and by the second light detector 32. The tilt of the PC bag 10 means that the light from the light source 21 is directed into the platelet concentrates 15 at an incident angle α.

[0070] Figure 5 A further embodiment of the device 1 is shown, which is essentially Figure 1A and Figure 1B The embodiment shown is similar to Figure 2A and Figure 2B In this embodiment, the apparatus 1 includes an optical system 20 comprising a first light source 21 and a second light source 24 configured to direct light into the platelet concentrates 15 in the PC bag carried by the removable bag holder 2 during a measurement interval. The detector system 30 of the apparatus 1 includes a first light detector 31 and a second light detector 32 configured to detect reflected light from the platelet concentrates 15 in the PC bag 10 during the measurement interval.

[0071] In this embodiment, the first light source 21 and the first and second light detectors 31 and 32 are arranged at a first side relative to the movable bag holder, while the second light source 24 is arranged at a second, opposite side relative to the movable bag holder.

[0072] The first light detector 31 is then arranged to detect reflected light originating from the first light source 21 , whereas the second light detector 32 is arranged to detect reflected light originating from the second light source 24 .

[0073] The controller 40 may be configured to activate both the first light source 21 and the second light source 24 simultaneously so that the first light detector 31 and the second light detector 32 detect reflected light during the same measurement interval. Alternatively, the controller 40 may activate the first light source 21 and the second light source 24 and the first light detector 31 and the second light detector 32 in sequence to alternate between detecting reflected light by the first light detector 31 during the first measurement interval and detecting reflected light by the second light detector 32 during the second measurement interval. The first measurement interval and the second measurement interval are preferably of the same duration, but may alternatively have different durations. As in Figure 3 and Figure 4 In the illustrated embodiment, a first real-time reflectivity signal and a second real-time reflectivity signal are generated by a first light detector 31 and a second light detector 32 , respectively.

[0074] In another embodiment, the real-time detection signal is a real-time transmittance signal, i.e., a signal representing light transmitted through the platelet concentrate in the PC bag during a measurement interval. In this embodiment, the detector system includes a light detector configured to detect light transmitted through the platelet concentrate in the PC bag during the measurement interval and to generate a real-time transmittance signal representing light transmitted through the platelet concentrate during the measurement interval. In this embodiment, the controller is configured to determine platelet swirl based on the real-time transmittance signal.

[0075] Figure 6A and Figure 6B An embodiment of an apparatus 1 suitable for real-time transmittance signal measurement is shown. In this embodiment, an optical system 20 of the apparatus 1 includes a light source 24 configured to direct light 25 through platelet concentrates 15 in a PC bag 10 carried by a removable bag holder during a measurement interval. In this embodiment, a detector system 30 of the apparatus 1 includes a light detector 31 configured to detect light 26 that passes through the platelet concentrates 15 in the PC bag 10 during the measurement interval and to generate a real-time transmittance signal representative of the light transmitted through the platelet concentrates 15 during the measurement interval.

[0076] In this embodiment, the controller 40 is configured to determine the platelet swirl of the concentrated platelets 15 in the PC bag 10 based on the real-time transmittance signal and determine a quality parameter of the concentrated platelets 15 in the PC bag 10 based on the platelet swirl.

[0077] exist Figure 6A and Figure 6B In the embodiment shown, the light system 20 and the detector system 30 thus each comprise a light source 24 and a light detector 31. The light detector 31 is arranged at a first side relative to the movable bag holder and the light source 24 is arranged at a second, opposite side relative to the movable bag holder.

[0078] 7A to 7C Another embodiment of the apparatus 1 is shown, comprising a light system 20 having a first light source 21 disposed at a first side relative to the removable bag holder and PC bag 10 and a second light source 24 disposed at a second, opposite side relative to the removable bag holder and PC bag 10. In this embodiment, the detector system 30 comprises a light detector 31 disposed at the first side relative to the removable bag holder and PC bag 10. The first light source 21 is then configured to direct light 22 at an incident angle α into the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder, see FIG. Figure 7B Correspondingly, the second light source 24 is configured to direct light 25 through the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder, see Figure 7C .

[0079] Therefore, in this embodiment, if 7A to 7C As shown, the device 1 has an optical system 20 including at least one light source 21 for real-time reflectivity measurement and at least one light source 24 for real-time transmittance measurement. The respective light sources 21, 24 are then arranged on either side of the PC bag 10, wherein the at least one light source 21 for real-time reflectivity measurement is on the same side relative to the PC bag 10 as the detector 31.

[0080] In an embodiment, a controller 40 is connected to the optical system 20 and the detector system 30. The controller 40 is configured to control the light source 24 of the optical system 20 to direct light 25 through the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder during a first measurement interval, and to control the light detector 31 of the detector system 30 to detect light 26 that has passed through the platelet concentrates 15 in the PC bag 10 during the first measurement interval and to generate a real-time transmittance signal. The controller 40 is also configured to control the light source 21 of the optical system 20 to direct light 22 at an incident angle α into the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder during a second measurement interval, and to control the light detector 31 of the detector system 30 to detect reflected light 23 from the platelet concentrates 15 in the PC bag 10 during the second measurement interval and to generate a real-time reflectance signal.

[0081] According to various embodiments, real-time reflectivity measurement and real-time transmittance measurement can be arranged. For example, 7A to 7C The device 1 in the embodiment may alternatively measure reflectivity and transmittance, or one of the reflectivity and transmittance may be measured more frequently than the other. In the above, real-time transmittance measurements are made during the first measurement interval, and real-time reflectivity measurements are made during the second measurement interval. The first measurement interval may precede the second measurement interval, or may follow the second measurement interval. Thus, in 7A to 7C In the illustrated embodiment, the real-time transmittance measurement may be performed before or after the real-time reflectance measurement.

[0082] In an embodiment, the controller 40 controls the light sources 21, 24 and preferably the detector 31 to perform real-time reflectance and / or transmittance measurements at scheduled measurement intervals (i.e., a first measurement interval and a second measurement interval). Thus, in an embodiment, the controller 40 is configured to control the first light source 21 to direct light 22 at an incident angle α into the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder ( Figure 7B ), and controlling the second light source 24 to direct light 25 through the concentrated platelets 15 in the PC bag 10 carried by the movable bag holder ( Figure 7CIn this embodiment, the optical system 20 includes a first light source 21 disposed at a first side relative to the movable bag holder and the PC bag 10, and a second light source 24 disposed at a second, opposite side relative to the movable bag holder and the PC bag 10. The detector system 30 includes a light detector 31 disposed at the first side relative to the movable bag holder and the PC bag 10. In this case, the controller 40 is preferably further configured to control the light detector 31 to detect reflected light 23 from the platelet concentrates in the PC bag 10 and generate a real-time reflectivity signal, and to control the light detector 31 to detect light 26 passing through the platelet concentrates 15 in the PC bag 10 and generate a real-time transmittance signal.

[0083] In an embodiment, the controller 40 is configured to alternately control the first light source 21 to direct light 22 at an incident angle α into the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder and control the second light source 24 to direct light 25 through the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder. Thus, in this particular embodiment, the apparatus 1 alternates between making real-time emissivity measurements and real-time transmittance measurements.

[0084] In an embodiment, the controller 40 is configured to determine a transmittance signal average based on the real-time transmittance signal and to determine the quality parameter based on the platelet swirl and the transmittance signal average.

[0085] As presented herein, experimental data indicate that the real-time detection signal (i.e., the real-time reflectance or transmittance signal) is a better indicator of platelet quality than the average transmittance signal. However, the average transmittance signal can be used in conjunction with the real-time detection signal to detect contaminants in platelet concentrates, such as by comparing Figure 10B and Figure 11B See also Figure 12 as well as Figure 13A and Figure 13B Therefore, the real-time detection signal accurately represents platelet swirl as well as platelet quality and changes as platelets degenerate and die. Furthermore, the real-time detection signal accurately reflects platelet quality independently of any microbial contaminants, as measured by comparing Figure 10A and Figure 11A See also Figure 12 as well as Figure 13A and Figure 13B If the real-time detection signal changes (see Figure 12 and Figure 13A ) along with the change in the average value of the transmittance signal (see Figure 12 and Figure 13A), then this indicates a decrease in platelet quality in the absence of any contaminants. However, if the change in the real-time detection signal is accompanied by essentially no change in the average transmittance signal, then this is an indication of degradation of platelet quality and contamination of the platelet concentrate 15, see Figure 12 and Figure 13B .

[0086] Thus, in an embodiment, the controller 40 is configured to determine platelet viability based on the real-time detection signal and to determine any cellular contaminants based on the transmittance signal average.

[0087] Figure 8 is a diagram of an apparatus 1 capable of performing both real-time reflectance and transmittance measurements according to another embodiment. In this embodiment, an optical system 20 includes a first light source 21 disposed at a first side relative to the removable bag holder and the PC bag 10 and a second light source 24 disposed at a second, opposite side relative to the removable bag holder and the PC bag 10, as described above in conjunction with 7A to 7C The detector system 30 includes a first detector 31 and a second detector 32 disposed on a first side relative to the removable bag holder and the PC bag 10. In this embodiment, the first light source 21 is configured to direct light 22 at an incident angle α onto the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder. The first light detector 31 is then configured to detect reflected light 23 from the platelet concentrates 15 in the PC bag 10 and generate a real-time reflectivity signal. The second light source 24 is configured to direct light 25 through the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder, and the second light detector 32 is configured to detect light 26 that has passed through the platelet concentrates 15 in the PC bag 10 and generate a real-time transmittance signal.

[0088] Therefore, if Figure 8 The embodiment shown has at least one pair of light source 21 and light detector 31 for real-time reflectivity measurement and at least one pair of light source 24 and light detector 32 for real-time transmittance measurement. Figure 8 The illustrated embodiment may be configured to perform real-time transmittance and reflectance measurements sequentially, as described above for 7A to 7C The embodiments shown are discussed or performed at least partially in parallel, ie at least partially simultaneously.

[0089] In one aspect of the present invention, the apparatus may be capable of performing real-time transmittance measurements, either alone or in combination with real-time reflectance measurements. In this aspect, an apparatus 1 for determining the quality of platelet concentrate 15 in a PC bag 10 includes a removable bag holder configured to carry the PC bag 10. The apparatus 1 also includes an optical system 20 comprising at least one light source 24 configured to direct light 25 through the platelet concentrate 15 in the PC bag 10 carried by the removable bag holder during a measurement interval. The apparatus 1 also includes a detector system 30 comprising at least one light detector 31, 32 configured to detect light 26 that passes through the platelet concentrate 15 in the PC bag 10 during a measurement interval and generate a real-time transmittance signal representative of the light transmitted through the platelet concentrate 15, preferably in real time. The apparatus 1 further includes a controller 40 connected to the detector system 30 and configured to determine the platelet swirl of the concentrated platelets 15 in the PC bag 10 based on the real-time transmittance signal and to determine a quality parameter of the concentrated platelets 15 in the PC bag 10 based on the platelet swirl.

[0090] In this regard, the real-time transmittance signal represents the real-time time light is transmitted through the platelet concentrate 15 during the measurement signal. Thus, the real-time transmittance signal represents the platelet swirl of the platelet concentrate 15 in the PC bag 10.

[0091] The real-time transmittance signal may be processed by the controller as discussed previously, such as calculating an average of the sample values and calculating the difference between each sample value and the calculated average.

[0092] The measurement interval is at least 0.5 s, preferably at least 1 s. In an embodiment, the measurement interval is no longer than 40 s, preferably no longer than 30 s, and more preferably no longer than 20 s. Therefore, in an embodiment, the measurement interval is selected in the range from 1 s to 20 s, such as 1 s, 2 s, 3 s, 4 s, 5 s, 6 s, 7 s, 8 s, 9 s, 10 s, 11 s, 12 s, 13 s, 14 s, 15 s, 16 s, 17 s, 18 s, 19 s or 20 s, preferably from 1 s to 10 s or from 1 s to 5 s.

[0093] In an embodiment, the device 1 comprises a motor 3 (see Figure 15 and Figure 16 ), the motor is configured to move the movable bag holder 2, such as horizontally back and forth ( Figure 15 ), or rotates around the axis of rotation 8 ( Figure 16In this embodiment, the controller 40 is preferably configured to control the motor 3 to temporarily stop the movement of the movable bag holder 2 at the beginning of the measurement interval or at least just before the beginning of the measurement interval. The controller 40 is also configured to activate the at least one light source 24 and control the at least one light source 24 to direct light 25 through the platelet concentrates 15 in the PC bag 10. In an embodiment, the controller 40 may also be configured to activate the at least one light detector 31, 32 and control the at least one light detector 31, 32 to detect light 26 that passes through the platelet concentrates 15 in the PC bag 10 during the measurement interval.

[0094] The temporary cessation of movement of the movable bag holder 2, and therefore of the platelet concentrate 15 in the PC bag 10 carried by the movable bag holder 2, causes movement of the platelets in the platelet concentrate 15, which is detected as a swirling effect by detecting light 26 passing through the platelet concentrate 10. This movement of the platelets in the platelet concentrate 15 typically takes the form of non-laminar flow or movement of the platelets within the PC bag 10. This (non-laminar) movement and thus the swirling effect after movement ceases depends on the mass of the platelets, caused by the change in the platelet form from the flat, rounded shape of viable platelets to the rounded shape of dead platelets. This means that the real-time detection signal generated by the at least one detector 31, 32 depends on the swirling effect of the platelets in the platelet concentrate 15.

[0095] A real-time reflectance or transmittance signal representing reflected light 23 or light 26 passing through platelet concentrate 15 detected over an extended period (i.e., during a measurement interval) more accurately reflects platelet swirl than a single instantaneous measurement or detection of transmitted light 26. Furthermore, detecting reflected light 23 or transmitted light 26 reflected from or passing through platelet concentrate 15 immediately after stopping movement of platelet concentrate 15 and PC bag 10, or at least in conjunction with stopping movement of the platelet concentrate 15 and PC bag 10, provides a more accurate representation of the swirl effect than a single detection of light 23, 26 as the platelet concentrate 15 passes by at least one light source 24 and at least one detector 31, 32 (i.e., without stopping movement of movable bag holder 2).

[0096] Figure 15 and Figure 16 Two different embodiments of an apparatus 1 for determining the quality of a platelet concentrate are shown. In both embodiments, 7A to 7C The optical system 20 and detector system 30 shown have been used as illustrative examples. In other embodiments, a detector system such as Figure 1A and Figure 1B 、 Figure 2A and Figure 2B 、 Figure 3 、 Figure 4 、 Figure 5 、 Figure 6A and Figure 6B or Figure 8 An optical system 20 and a detector system 30 are shown.

[0097] The apparatus 1 includes a cabinet or cupboard 6 that encloses one or more (i.e., at least two) removable bag holders 2, each of which carries one or more PC bags 10. The cabinet 6 preferably has a door (not shown) that can be opened to allow the PC bags 10 to be placed on and retrieved from the removable bag holders 2. The door is normally closed to maintain a controlled internal environment within the cabinet 6. This environmental control is preferably achieved using equipment 4 configured to maintain a controlled internal environment. Such equipment 4 may include temperature control equipment (such as a heater and / or a cooler) to maintain the temperature inside the cabinet 6 within a preferred range, such as approximately 20 to 22°C. The equipment 4 may also include equipment for controlling the oxygen concentration (oxygen partial pressure), carbon dioxide concentration (carbon dioxide partial pressure), and / or water vapor content inside the cabinet 6.

[0098] Figure 15 The apparatus 1 shown comprises a movable bag holder 2 which is movable horizontally, as indicated by the double-headed arrow. The apparatus 1 then comprises a motor 3 for moving the movable bag holder 2 horizontally back and forth. The motor 3 and the movable bag holder 2 thereby provide agitation of the platelet concentrate 15 in the PC bag 10. Thus, in an embodiment, the apparatus 1 is used, for example, The rollers provide continuous lateral motion and slides to allow the PC bag 10 to move and agitate on the movable bag holder 2. This agitation serves to prevent platelet aggregation and optimize the oxygenation of the platelets in the PC bag 10.

[0099] Figure 16 Another embodiment of the apparatus 1 is shown. In this embodiment, at least one movable bag holder 2 is rotatable about an axis of rotation 8 and forms an oblique angle with the vertical axis. The apparatus 1 further comprises a motor 3 for rotating the movable bag holder 2 about the axis of rotation 8 as indicated by the arrow. For example, the apparatus 1 may contain a rotor 7 which is aligned with the axis of rotation 8 and supports one or more parallel planes or discs as the movable bag holder 2. In an embodiment, the rotor 7 and the axis of rotation 8 are inclined so that each PC bag 10 on the movable bag holder 2 moves between different vertical positions within the cabinet 6 during one complete rotation, i.e., through a higher point and a lowest point. In this embodiment, at least one light source 21, 24 and at least one light detector 31 are preferably arranged near the lowest point of the bag holder 2, as Figure 16 shown.

[0100] The desired agitation of the platelet concentrates in the PC bag 10 is achieved by moving the bag holder 2 around the Figure 16 This is achieved by rotating the axis of rotation 8 in the embodiment.

[0101] The removable bag holder 2 may optionally include an opening or aperture 5 that aligns with the PC bag 10, such as Figure 15 and Figure 16 This aperture 5 then enables light from the light source 24 to pass through the platelet concentrates in the PC bag 10 and the removable bag holder 2 to reach the detector 31 .

[0102] like Figure 15 The device 1 shown is superior to the Figure 16 An advantage of the device shown is that light measurements can be performed without stopping the movement of the movable bag holder 2. Figure 16 In the device 1, the rotation of the rotor 7 and the bag holder 2 must generally be stopped in order to be able to provide a sufficient light measurement interval. However, if the rotation of the movable bag holder 2 is kept sufficiently slow and the detection response of the at least one light detector 31 is sufficiently fast, then even in the case of continuous rotation of the movable bag holder 2, it is possible to use Figure 16 Device 1 in performs light measurement.

[0103] The at least one light source 21, 24 of the light system 20 can be any light source capable of providing light into and optionally through the platelet concentrate. In an embodiment, the at least one light source is at least one broadband light source 21, 24 configured to emit light in the visible spectrum, such as white light. In other embodiments, the light source can emit light within a selected range of the visible spectrum or indeed outside the visible spectrum, such as in the infrared (IR) or near infrared (NIR) spectrum. One or more light sources configured to emit light in multiple ranges of the visible spectrum can also be used. Non-limiting examples of the light sources 21, 24 of the device 1 include light emitting diodes (LEDs), such as white LEDs, any color LEDs, IR LEDs, or NIR LEDs, and halogen bulbs.

[0104] The at least one light detector 31, 32 can be any detector capable of detecting reflected light and / or transmitted light from the platelet concentrate 15. Non-limiting examples of the light detectors 31, 32 of the apparatus 1 are photodiodes. Other examples of the light detectors 31, 32 include avalanche photodiodes (APDs) and silicon photomultipliers (SiPMs).

[0105] Another aspect of the embodiment relates to a method of determining the quality of the platelet concentrate 15 in the PC bag 10, see Figure 17The method includes, in step S1, directing light 22, 25 into platelet concentrate 15 in a PC bag 10 carried by a removable bag holder 2 configured to carry the PC bag 10 and agitate the platelets in the PC bag 10 during or within a measurement interval. The method also includes, in step S2, detecting light 23, 36 from the platelet concentrate 15 in the PC bag 10, and, in step S3, generating a real-time detection signal based on the detected light 23, 26. The method also includes, in step S4, determining a platelet swirl of the platelet concentrate 15 in the PC bag 10 based on the real-time detection signal, and, in step S5, determining a quality parameter of the platelet concentrate 15 in the PC bag 10 based on the platelet swirl.

[0106] Method steps S1 to S5 are preferably performed multiple times, as indicated by line L1 , to determine and monitor quality parameters of the platelet concentrate over time.

[0107] In an embodiment, the real-time detection signal includes a plurality of signal samples having corresponding sample values. In this embodiment, the method includes calculating an average of the sample values of the signal samples. In this embodiment, step S4 includes determining the platelet swirl based on the calculated points and data points of the sample values of the signal samples.

[0108] In a particular embodiment, the method comprises calculating, for each signal sample of the real-time detection signal, a difference between a sample value of the signal sample and a calculated average value. In this particular embodiment, step S4 comprises determining the platelet swirl based on the calculated difference, preferably based on the sum of the calculated differences.

[0109] In an embodiment, step S2 includes detecting reflected light 23 from the platelet concentrate 15 in the PC bag 10 during the measurement interval, and step S3 includes generating a real-time reflectance signal representative of the light reflected from the platelet concentrate 10 during the measurement interval.

[0110] In an embodiment, step S1 includes directing light 22 into the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder 2 at an incident angle α selected within the interval from 5° to 85° during a measurement interval. In this embodiment, step S2 includes detecting reflected light 23 from the platelet concentrates 15 in the PC bag 10 during the measurement interval, and step S3 includes generating a real-time reflectance signal representative of the light reflected from the platelet concentrates 10 during the measurement interval.

[0111] In another embodiment, Figure 17In this embodiment, step S1 includes directing light 25 through the platelet concentrate 15 in the PC bag 10 carried by the removable bag holder 2 during a measurement interval. In this embodiment, step S2 includes detecting light 26 that has passed through the platelet concentrate 15 in the PC bag 10 during the measurement interval. In this embodiment, step S3 includes generating a real-time transmittance signal representative of the light transmitted through the platelet concentrate 15 during the measurement interval.

[0112] In an embodiment, step S1 includes directing light 25 through the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder 2 during a first measurement interval, and directing light 22 into the platelet concentrates 15 in the PC bag 10 carried by the removable bag holder 2 at an angle of incidence α selected from a range of 5° to 85° during either the first or second measurement interval. In this embodiment, step S2 includes detecting light 26 that passes through the platelet concentrates 15 in the PC bag 10 during the first measurement interval, and detecting light 23 reflected from the platelet concentrates 15 in the PC bag 10 during either the first or second measurement interval. Step S3 includes generating a real-time transmittance signal representing light transmitted through the platelet concentrates 15 during the first measurement interval, and generating a real-time reflectance signal representing light reflected from the platelet concentrates 10 during either the first or second measurement interval. In this embodiment, step S4 includes determining platelet swirl of the platelet concentrates 15 in the PC bag 10 based on the real-time reflectance signal and / or the real-time transmittance signal.

[0113] In this embodiment, a single, identical measurement interval (i.e., the first measurement interval) can be used for both the reflectance measurement and the transmittance measurement. Alternatively, the measurement interval for the transmittance measurement can be considered the first measurement interval, which can be different from the measurement interval for the reflectance measurement (which can be considered the second measurement interval), for example having a different duration and / or occurring at a different point in time.

[0114] In an embodiment, the method comprises an additional step S10, such as Figure 18 The method continues from step S3 or S4. Step S10 includes determining the transmittance signal average value based on the real-time transmittance signal. The method then continues to Figure 17 In this embodiment, step S5 comprises determining a quality parameter based on the platelet swirl and the average value of the transmittance signal.

[0115] In an embodiment, step S5 comprises determining platelet viability based on platelet swirl and determining any cellular contaminants based on the transmittance signal average.

[0116] Figure 19 It shows Figure 17Flowchart of additional optional steps of the method shown. In an embodiment, the method comprises, in step S20, temporarily stopping the movement of the movable bag holder 2 at the beginning of the measurement interval or at least just before the beginning of the measurement interval. In another embodiment, this step S20 comprises temporarily changing the movement of the movable bag holder 2 at the beginning of the measurement interval or at least just before the beginning of the measurement interval. In either case, the method then continues to Figure 17 Step S1 in .

[0117] Example

[0118] Materials and methods

[0119] Sample preparation

[0120] PC samples were prepared by combining sufficient quantities of compatible PC samples to yield a volume of approximately 500 mL. This volume was divided into two aliquots of approximately 250 mL each, one of which was subsequently contaminated ("spiked") with Staphylococcus epidermidis (i.e., a common skin bacterium). Both aliquots were filled into standard PC storage bags.

[0121] Measuring equipment

[0122] like Figure 15 The device of the present invention (referred to herein as PlateGuard TM ) equipped with Figure 7A The measurement setup is capable of measuring transmission and reflection alternately. Real-time transmission and reflection data are recorded and used to calculate the average value (mean) of the signal to obtain the transmission mean (TM) ("turbidity") and the reflection mean (RM), as well as the time-dependent detection signal (signal intensity of the signal). It represents a quantitative determination of the swirl, ie the transmitted swirl (TS) and the reflected swirl (RS) are obtained.

[0123] Measurement process

[0124] Immediately after preparation, TM The device was loaded with two prepared PC bags. Immediately after preparation and at the same time in the morning of each following weekday, a small sample (about 10 mL) was taken from each bag for laboratory analysis. In general, laboratory analysis was performed 1 day, 2 days, 3 days, 4 days, and 8 days after expiration.

[0125] Store PC bags in PlateGuard TM The device was placed in the chamber for 8 days. During this time, the four parameters RM, RS, TM and TS were collected from both bags in rapid sequence (approximately one parameter per minute). The collected data were stored for analysis until after the 8-day run time.

[0126] result

[0127] Figure 13A and Figure 13B The time evolution of the parameters TM and RS for the unspiked and spiked samples is shown, respectively. Figure 12 This variation is shown as a combined curve.

[0128] Figure 13A It was shown that the TM signal ("turbidity") changes almost linearly with time, which was interpreted as platelet degradation in WO 90 / 14588 and US 6,288,778. However, when the turbidity of the platelet concentrate is changed due to bacterial growth in the platelet concentrate, the TM signal behaves significantly differently ( Figure 13B ). However, the RS signal ("swirl") was not affected by the change in turbidity and was almost identical in spiked and unspiked platelet concentrates and thus represents true platelet swirl.

[0129] Figure 14A and Figure 14B Graphs were compared for various methods of interpreting platelet viability, including visual inspection of the swirl effect by an experienced operator (range 0 to 3) (SW), PlateGuard TM Quantitative determination of swirl by the device (RS); and various laboratory methods for determining platelet viability (F1 to F6): aggregation at 16 μM collagen (F1), at 8 μM collagen (F2), at 0.5 mg / ml arachidonic acid (ARA) (F5), and at 20 μM thrombin receptor activating peptide (TRAP) (F6).

[0130] The RS signal showed an almost linear trend in the swirl effect, while an experienced operator's eye could not detect any changes until after 4 days. Laboratory data showed that platelets had already degenerated dramatically by day 3, while the swirl effect was still good. However, the RS according to the present invention showed that the quantitative determination of the swirl was reduced to 60% of the initial value.

[0131] in conclusion

[0132] The present invention provides a quantitative determination of swirl, which in turn is a good indicator of platelet viability. Monitoring of platelet quality according to the present invention can even be performed in the presence of bacterial growth, which would otherwise contaminate the average transmission signal, i.e., turbidity, and thus the quality would not be indicative of platelet viability in the presence of microbial contaminants.

[0133] The above embodiments should be understood as some illustrative examples of the present invention. Those skilled in the art will understand that various modifications, combinations, and changes may be made to the embodiments without departing from the scope of the present invention. In particular, different partial solutions in different embodiments may be combined into other configurations where technically feasible. However, the scope of the present invention is defined by the appended claims.

Claims

1. An apparatus (1) for determining the quality of concentrated platelets (15) in a platelet concentrate (PC) bag (10), the apparatus (1) comprising: a movable bag holder (2) configured to carry the PC bag (10) and agitate the platelets in the PC bag (10); a light system (20) comprising at least one light source (21, 24) configured to direct light (22) into the concentrated platelets (15) in the PC bag (10) carried by the removable bag holder (2) and to direct light (25) through the concentrated platelets (15) during a measurement interval; a detector system (30) comprising at least one light detector (31, 32) configured to detect reflected light (23) from the concentrated platelets (15) in the PC bag (10) during the measurement interval and generate a real-time reflectivity signal representative of light reflected from the concentrated platelets (15) during the measurement interval, and to detect light (26) passing through the concentrated platelets (15) during the measurement interval and generate a real-time transmittance signal representative of light transmitted through the concentrated platelets (15) during the measurement interval; and a controller (40) connected to the detector system (30) and configured to: determining a platelet swirl of the concentrated platelets (15) in the PC bag (10) based on the real-time reflectivity signal; determining a transmittance signal average based on the real-time transmittance signal; determining platelet viability of the concentrated platelets (15) in the PC bag (10) based on the platelet swirl; and The presence or absence of any cellular contaminants is determined based on the transmittance signal average.

2. The device according to claim 1, wherein The real-time reflectivity signal comprises a plurality of signal samples having corresponding sample values; and The controller (40) is configured to calculating an average of the sample values of the signal samples; and The platelet swirl is determined based on the calculated average of the signal samples and the sample value.

3. The apparatus according to claim 2, wherein the controller (40) is configured to calculating, for each signal sample of the real-time reflectivity signal, a difference between the sample value of the signal sample and the calculated average value; and The platelet swirl is determined based on the calculated difference.

4. The apparatus of claim 3, wherein the controller (40) is configured to determine the platelet swirl based on a sum of the calculated differences.

5. The apparatus according to claim 4, wherein the controller (40) is configured to or to determine the platelet swirl, wherein the real-time reflectivity signal comprises N signal samples within the measurement interval, s i represents the sample value at sample number i, i = 1...N, and represents the average value of the calculation.

6. The device according to any one of claims 1 to 5, wherein the optical system (20) comprises: a first light source (21) configured to direct light (22) into the concentrated platelets (15) in the PC bag (10) carried by the movable bag holder (2) at an incident angle (α) selected within the interval from 5° to 85° during the measurement interval; as well as A second light source (24) is configured to direct light (25) through the platelet concentrate (15) in the PC bag (10) carried by the removable bag holder (2) during the measurement interval.

7. The apparatus according to claim 6, wherein The first light source (21) is arranged at a first side relative to the movable bag holder (2); The second light source (24) is arranged at a second opposite side relative to the movable bag holder (2); and A first light detector (31) in the detector system (30) is arranged at the first side relative to the movable bag holder (2).

8. The apparatus according to claim 6, wherein the first light source (21) is configured to direct light (22) into the concentrated platelets (15) in the PC bag (10) carried by the movable bag holder (2) at an incident angle (α) selected in the interval from 15° to 85° during the measurement interval.

9. The device according to claim 8, wherein the angle of incidence (α) is selected from the interval 25° to 85°.

10. The device according to claim 9, wherein the angle of incidence (α) is selected from the interval 45° to 75°.

11. The apparatus according to claim 7, wherein The detector system (30) includes the first light detector (31) and the second light detector (32) arranged at the first side relative to the movable bag holder (2); The first light detector (31) is configured to detect reflected light (23) from the concentrated platelets (15) in the PC bag (10) during the measurement interval and generate the real-time reflectivity signal; and The second light detector (32) is configured to detect light (26) passing through the concentrated platelets (15) in the PC bag (10) during the measurement interval and generate the real-time transmittance signal.

12. The apparatus according to any one of claims 1 to 5, wherein the measurement interval has a duration selected in the range from 0.5 s up to 40 s.

13. The apparatus according to claim 12, wherein the measurement interval has a duration selected in the range from 1 s up to 30 s.

14. The apparatus according to claim 13, wherein the measurement interval has a duration selected in the range from 1 s up to 20 s.

15. The apparatus according to any one of claims 1 to 5, wherein The movable bag holder (2) is movable horizontally; and The device (1) also includes a motor (3) for moving the movable bag holder (2) back and forth horizontally.

16. The apparatus according to any one of claims 1 to 5, wherein The movable bag holder (2) is rotatable about an axis of rotation (8); and The device (1) further comprises a motor (3) for rotating the movable bag holder (2) about the rotation axis (8).

17. Apparatus according to any one of claims 1 to 5, wherein the controller (40) is configured to temporarily stop the movement of the movable bag holder (2) at the start of the measurement interval or at least just before the start of the measurement interval.

18. Apparatus according to any one of claims 1 to 5, wherein the controller (40) is configured to temporarily change the movement of the movable bag holder (2) at the start of the measurement interval or at least just before the start of the measurement interval.

19. Apparatus according to any one of claims 1 to 5, wherein the at least one light source (21, 24) is configured to emit light (22, 25) within the visible spectrum or within at least one selected range of the visible spectrum.

20. A method of determining the quality of platelet concentrates (15) in a platelet concentrate (PC) bag (10), the method comprising: directing (S1) light (22, 25) into and through the concentrated platelets (15) in the PC bag (10) carried by a removable bag holder (2), the removable bag holder being configured to carry the PC bag (10) and agitate the platelets in the PC bag (10), during a measurement interval; detecting (S2) reflected light (23) from the concentrated platelets (15) in the PC bag (10) during the measurement interval and detecting (S2) light (26) passing through the concentrated platelets (15) in the PC bag (10) during the measurement interval; generating (S3) a real-time reflectivity signal based on the reflected light (23) and generating (S3) a real-time transmittance signal representative of light transmitted through the concentrated platelet (15) during the measurement interval; determining (S4) a platelet swirl of the concentrated platelets (15) in the PC bag (10) based on the real-time reflectivity signal; determining a transmittance signal average based on the real-time transmittance signal; determining (S5) platelet viability of the concentrated platelets (15) in the PC bag (10) based on the platelet swirl; as well as The presence or absence of any cellular contaminants is determined based on the transmittance signal average.

21. A method according to claim 20, wherein the real-time reflectivity signal includes multiple signal samples having corresponding sample values, and the method further includes calculating an average of the sample values of the signal samples, wherein determining (S4) the platelet swirl includes determining (S4) the platelet swirl based on the calculated points and data points of the sample values of the signal samples.

22. The method according to claim 21 further includes calculating, for each signal sample of the real-time reflectivity signal, a difference between the sample value of the signal sample and the calculated average value, and wherein determining (S4) the platelet swirl includes determining (S4) the platelet swirl based on the calculated difference.

23. The method of claim 22, wherein determining (S4) the platelet swirl comprises determining (S4) the platelet swirl based on a sum of the calculated differences.

24. The method of claim 23, wherein determining (S4) the platelet swirl comprises determining the platelet swirl based on or to determine (S4) the platelet swirl, wherein the real-time reflectivity signal comprises N signal samples within the measurement interval, s i represents the sample value at sample number i, i = 1...N, and represents the average value of the calculation.

25. The method according to any one of claims 20 to 24, wherein directing (S1) the light (22) comprises: Light (22) is directed (S1) into the concentrated platelets (15) in the PC bag (10) carried by the movable bag holder (2) at an incident angle (α) selected in the interval from 5° to 85° during the measurement interval, and light (25) is directed through the concentrated platelets (15) in the PC bag (10) carried by the movable bag holder (2).

26. The method according to any one of claims 20 to 24, further comprising temporarily stopping (S20) the movement of the movable bag holder (2) at the beginning of the measuring interval or at least just before the beginning of the measuring interval.

27. The method according to any one of claims 20 to 24, further comprising temporarily changing (S20) the movement of the movable bag holder (2) at the beginning of the measuring interval or at least just before the beginning of the measuring interval.

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