Medical sample transportation container
12247192 ยท 2025-03-11
Assignee
Inventors
- Jonas Jarvius (Uppsala, SE)
- Anders Lind (Tarnsjo, SE)
- Henrik Soderstrom (Knivsta, SE)
- Jan Grawe (Uppsala, SE)
- Ian Fitzpatrick (Elwood, AU)
- Jurg Bartholdi (San Diego, CA, US)
Cpc classification
A01N1/144
HUMAN NECESSITIES
A01N1/148
HUMAN NECESSITIES
International classification
C12M3/00
CHEMISTRY; METALLURGY
A01N1/00
HUMAN NECESSITIES
C12M1/02
CHEMISTRY; METALLURGY
C12M3/06
CHEMISTRY; METALLURGY
Abstract
A portable apparatus and method for transport and incubation of a medical sample in a blood culture flask includes a sealable container having a thermally insulated compartment for receiving the blood culture flask and a heater for heating the medical sample to a temperature suitable for pre-culturing of the sample. An agitator is provided for agitating the sample in the blood culture flask.
Claims
1. A method for handling a medical sample in a blood culture flask, wherein the medical sample is a blood sample, and wherein the method includes simultaneous transportation and incubation of the medical sample in a portable, hand-held apparatus for transport and incubation of the medical sample, the apparatus comprising a sealable container having a thermally insulated compartment for receiving the blood culture flask; a heater; and an agitator, and comprises: placing the blood culture flask in the thermally insulated compartment of the sealable container; transporting the medical sample; pre-culturing the medical sample by, with the heater, heating the medical sample to a temperature suitable for pre-culturing to promote growth of microorganisms, wherein the thermally insulated compartment and the heating are used to keep the medical sample at the temperature suitable for pre-culturing during the transporting of the medical sample; and with the agitator, agitating the medical sample in the blood culture flask during transportation and pre-culturing of the medical sample.
2. The method as claimed in claim 1, further comprising, after pre-culturing during transport in the thermally insulated compartment, testing of the medical sample for the purpose of detecting and characterizing a microorganism in the medical sample.
3. The method as claimed in claim 1, further comprising timing the amount of time for which the sample has been pre-cultured.
4. The method as claimed in claim 3, wherein the timing is started automatically by loading the sample into the container.
5. The method as claimed in claim 3, wherein the timing is manually started by a user.
6. The method as claimed in claim 3, further comprising displaying the amount of time for which the sample has been pre-cultured.
7. The method as claimed in claim 1, wherein the heating is done by an electrical heater.
8. The method as claimed in claim 1, further comprising controlling the agitator to apply a predetermined degree of agitation.
9. The method as claimed in claim 1, further comprising agitating the sample constantly or intermittently.
10. The method as claimed in claim 1, further comprising controlling the degree of heating to maintain a pre-set temperature.
11. The method as claimed in claim 1, further comprising monitoring the temperature in the compartment and optionally controlling the degree of heating to maintain a pre-set temperature based on the monitored temperature.
12. The method as claimed in claim 1, further comprising monitoring, using an accelerometer, the agitation of the blood culture flask.
13. The method as claimed in claim 1, further comprising determining whether the sample is positive for microbial growth.
14. The method as claimed in claim 1, further comprising maintaining the sample at a temperature of 25 C. to 45 C.
15. The method as claimed in claim 1, further comprising maintaining the sample at a temperature of 30 C. to 37 C.
16. The method as claimed in claim 1, wherein the agitating includes rotating the blood culture flask about a main axis of the blood culture flask.
17. The method as claimed in claim 1, further comprising removing a test aliquot from the blood culture flask, continuing to culture the medical sample in the blood culture flask, separating DNA from the test aliquot, and performing nucleic acid tests on the DNA to identify a microorganism and to detect the presence or absence of one or more genetic antimicrobial resistance markers in the microorganism.
18. The method as claimed in claim 17, wherein the nucleic acid tests are performed using i) one or more nucleic acid probes and/or primers for microbial identification, a probe or primer thereof being capable of hybridizing specifically to, or a primer thereof being capable of selectively amplifying, a nucleotide sequence which is identificatory of a given microorganism; and ii) one or more nucleic acid probes and/or primers for antimicrobial resistance marker detection, a probe or primer thereof being capable of hybridizing specifically to, or a primer thereof being capable of selectively amplifying, a nucleotide sequence representing a genetic antimicrobial resistance marker.
19. The method as claimed in claim 17, comprising, detecting whether or not the probes and/or primers have hybridized to the DNA and/or the primers have been extended, and if a microorganism is identified in the nucleic acid tests, performing an antimicrobial susceptibility test on a cultured medical sample obtained from the blood culture flask after the continued culturing wherein microbial growth in the antimicrobial susceptibility test is monitored by assessing growth or markers for growth, and wherein the type and concentration of antimicrobial agents used in the antimicrobial susceptibility test is determined by the identity of the microorganism and antimicrobial resistance markers detected by the nucleic acid tests, and optionally continuing to culture the medical sample in the blood culture flask; or if no microorganism strain is identified in by the nucleic acid tests then the method includes further culturing the medical sample to enable further microbial identification and antimicrobial susceptibility tests to be performed to identify the microorganism and determine its antimicrobial resistance profile.
20. The method as claimed in claim 1, wherein the blood culture flask comprises a septum to be perforated for inoculating the flask and subsequently sampling from the flask.
Description
(1) Preferred embodiments of the present invention will now be described by reference to the accompanying figures, in which:
(2)
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(7)
(8)
(9) The container 1 shown in
(10) The container 1 is sealed with a lid 5 which may comprise a sealing O-ring 19 (as shown in
(11) The exterior of the container may include a label (not shown) on which can be written the time at which the sample began pre-culturing (i.e. the time at which the heater was activated).
(12) The container shown in
(13) To address this, instead of the chemical heater of
(14) The controller may also set running a timer 14 when the heater is activated. The time recorded on the timer may be displayed on an LCD display 15 mounted on an external surface of the container 1. The controller is also operable to control an agitator 16. The agitator 16 shakes the blood culture flask continuously or intermittently in order to aerate the sample. The agitator 16 device is controlled by the controller. The agitation may be recorded by an accelerometer 20 to measure the degree of agitation during transportation. The degree of agitation recorded by the accelerometer timer is displayed on the LCD display 15. Each of the resistance heater 11, controller 12, temperature sensor 13, timer 14, LCD display 15, agitator 16 and accelerometer 20 may be powered by a power supply unit (PSU) 17 (not shown on
(15)
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(17) The agitator 16 comprises a motor 16a, a rotating wheel 16b, a sleeve 16c which receives the blood culture flask 2, a off-centre coupling engagement 16d between the sleeve 16c and the rotating cam wheel 16b, and two lock rings 16e which attach the sleeve 16c to the compartment 3 approximately half way along the length of the blood culture flask 2 and at the base of the blood culture flask 2. The motor 16a is separated from the sleeve 16c and the rotating wheel 16b by a motor plate 22, which also provides a mounting point for supporting the motor 16a.
(18) As the motor 16a rotates, the rotating wheel 16b is also driven to rotate, and correspondingly rotates the blood culture flask 2 via the connection of the coupling engagement 16d to the sleeve 16c which holds the blood culture flask 2. The connection of the sleeve 16c to the rotating wheel 16b is such that the axis of symmetry of the blood culture flask 2 is misaligned with the axis of rotation of the motor 16a and cam wheel 16b, and the two axes are non-parallel, such that the blood culture flask 2 rotates in an off-axial manner, fixed in place at the lock ring 16e. In this example this axial misalignment is achieved by the use of a coupling arrangement 16d having a key that cannot be fully fitted within the corresponding recess, such that the key forces the base of the sleeve 16c at one side to be spaced apart from the surface of the rotating wheel 16b, whilst the base of the flask can be closer to or indeed touching the rotating wheel 16b on the other side. This means that the base of the sleeve 16c, and hence the base of the flask 2, is not parallel with the radial direction of the wheel 16b and therefore the axis of rotational symmetry of the flask 2 is not parallel with the axis of rotation of the wheel 16b.
(19) The agitator 16 thus agitates the blood culture flask 2 by movement of the sleeve 16c when the motor 16c rotates the wheel 16b. The sleeve 16c fits closely to the blood culture flask 2, which is a flask 2 of standardised size and hence known dimensions. The sleeve 16c has flexible tine portions at its open end that are arranged to resiliently deform during insertion and removal of the blood culture flask 2. As shown in
(20) The motor 16a is powered by a battery pack 17, which is accessed (for replacement or wired re-charging) via a bottom lid 18. The agitator 16 is controlled by a controller 12, which in this example is a PCB. The motor 16a is advantageously contained within the thermally insulated volume of the thermally insulated compartment 3 such that waste heat from the motor 16a can contribute to heating of the medical sample in the blood culture flask 2.
(21) The thermally insulated compartment 3 comprises thermally insulating material (not shown in all Figures) about the container and with a thickness sufficient to allow the heater to maintain the required temperature. The nature of the thermal insulation can be varied, provided that it provides the necessary reduction in heat loss. Silica aerogel, expanded polyurethane, expanded polystyrene or urea foam may be used, for example.
(22) Optionally the portable apparatus can include a sensor for determining if the sample is positive, as well as an indicator for showing if the sample is positive or not. The indicator may be a light or some other form of display, such as an LCD display. One possibility is to use an optical sensor such as a photodetector (as used, for example, in in EP 2828398) to identify changes in the turbidity of the sample. The optical sensor can be mounted within the sleeve around the flask in the example of
(23) The battery pack 17 can arranged to receive power for recharging the battery from a charging point via a wired connection or via wireless power transmission such as inductive power transfer. The portable apparatus can be provided with a charging point (not shown) that connects to mains electricity and is arranged to charge multiple portable apparatuses simultaneously, for example more than 10 or more than 50 devices. The charging point could hence be provided with multiple inductive charging pads and/or multiple leads allowing for connection to many portable devices. A large hospital could pre-culture up to 250 samples per day, but in batches so a charge station of up to 50 (100 at most) would suit most needs. Smaller medical institutions could manage with a smaller charging capability, for example 5-10 or 10-50 devices at once.
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(25) The sleeve 16c of this example is held by a pair of pivots 16g on the yoke 16f at a point above the centre of mass of the sleeve 16c and the blood culture flask 2.
(26) A portable apparatus as described in relation to any of the examples above can be used for transportation of a medical sample whilst pre-culturing the medical sample. Thus, the apparatus is used for samples requiring pre-culturing and in particular for samples that have been provided for testing using methods that are not harmed by pre-culturing. For certain testing methods, for example the method as described in WO2015/189390, pre-culturing is an advantage and the use of a portable apparatus for simultaneous pre-culturing and transport of the medical sample for such methods will provide significant advantages in relation to the speed of processing of the samples and the total time required before the results of the testing process are available. Thus, the portable apparatus may be provided as a part of a broader testing system for testing a medical sample. An embodiment hence provides a medical sample testing system comprising: the portable apparatus as described, for example, with reference to any of
(27) The medical sample processing system may be a microorganism detection device for detecting and characterising a microorganism in the medical sample similar to that described in WO2015/189390, and hence in one example the portable apparatus is used together with a device comprising a test aliquot extraction device for removing a portion of the contents of the blood culture flask for use as a test aliquot; a culturing device for culturing the medical sample in the blood culture vessel after extraction of the test aliquot, and optionally before extraction of the test aliquot; and a DNA testing device for separating DNA from the test aliquot, and performing nucleic acid tests on the DNA to identify the microorganism and to detect the presence or absence of one or more genetic antimicrobial resistance markers in the microorganism.
(28) The DNA testing device is arranged to perform the nucleic acid tests using: i. one or more nucleic acid probes or primers for microbial identification, the probe or primer being capable of hybridising specifically to, or a the primer being capable of selectively amplifying, a nucleotide sequence which is identificatory of a given microorganism; and ii. one or more nucleic acid probes or primers for antimicrobial resistance marker detection, a probe or primer thereof being capable of hybridising to, or a primer thereof being capable of selectively amplifying, a nucleotide sequence representing a genetic antimicrobial resistance marker; and it is detected whether or not the probe(s) or primer(s_ have hybridised to the DNA and/or whether or not the primer(s) have taken part in an amplification reaction; wherein the microorganism detection device is arranged such that: if the given microorganism is identified by the DNA testing device, then the cultured clinical sample produced by the culture vessel by culturing after extraction of the test aliquot is passed to an antimicrobial susceptibility test device for performing antimicrobial susceptibility test on the cultured clinical sample by monitoring microbial growth by assessing growth or markers for growth, and wherein the type and concentration of antimicrobial agents used in the antimicrobial susceptibility test is determined by the identity of the microorganism and antimicrobial resistance markers detected by the DNA testing device; and if the given microorganism is not identified by the DNA testing device, then the microorganism detection device further cultures the clinical sample in the culture vessel to enable further microbial identification and antimicrobial susceptibility tests to be performed after additional culturing in order to identify the microorganism and determine its antimicrobial resistance profile.
(29) An example of a method for handling a medical sample in a blood culture flask including transporting the medical sample (advantageously using the apparatus described above) as well as testing the medical sample after pre-culturing during transport. The method comprises: placing the blood culture flask in a thermally insulated compartment of a sealable container; heating the medical sample to a temperature suitable for pre-culturing of the sample, wherein the thermally insulated compartment and the heating are used to keep the medical sample at the temperature suitable for pre-culturing during transport of the sample; and mechanically agitating the blood culture flask to thereby agitate the sample during transport.
(30) The subsequent testing of the medical sample, optionally after further culturing, includes removing a test aliquot from the blood culture flask, continuing to culture the medical sample in the blood culture flask, separating DNA from the test aliquot, and performing nucleic acid tests on the DNA to identify a microorganism and to detect the presence or absence of one or more genetic antimicrobial resistance markers in the microorganism
(31) The nucleic acid tests are performed using: i) one or more nucleic acid probes and/or primers for microbial identification, a probe or primer thereof being capable of hybridising specifically to, or a primer thereof being capable of selectively amplifying, a nucleotide sequence which is identificatory of a given microorganism; and ii) one or more nucleic acid probes and/or primers for antimicrobial resistance marker detection, a probe or primer thereof being capable of hybridising specifically to, or a primer thereof being capable of selectively amplifying, a nucleotide sequence representing a genetic antimicrobial resistance marker.
(32) It is detected whether or not the probes and/or primers have hybridised to the DNA and/or the primers have been extended (e.g. an amplification reaction has taken place); and if a microorganism is identified in the nucleic acid tests then the method includes performing an antimicrobial susceptibility test on a cultured medical sample obtained from the blood culture flask after the continued culturing, wherein microbial growth in the antimicrobial susceptibility test is monitored by assessing growth or markers for growth, and wherein the type and concentration of antimicrobial agents used in the antimicrobial susceptibility test is determined by the identity of the microorganism and antimicrobial resistance markers detected by the nucleic acid tests, and optionally continuing to culture the medical sample in the blood culture flask; or if no microorganism strain is identified in by the nucleic acid tests then the method includes further culturing the medical sample to enable further microbial identification and antimicrobial susceptibility tests to be performed to identify the microorganism and determine its antimicrobial resistance profile.
(33) The proposed methods and devices described herein allow for pre-culturing of a medical sample whilst it is in transport. This provides clear advantages in relation to the total time for processing of a sample.
(34) In medical diagnostics the time to result is often communicated as the time from which a sample is put into a system to time lab result is obtained. For the patient the key issue is of course time to answer from when the clinical sample is taken from the patient to when a lab result is obtained, communicated to treating MD and action taken. The proposed methods and devices provide a way to reduce time-to-action for a microbiology in vitro diagnostic system, measured from the time that clinical sample taken until the time that action can be taken to treat the patient.
(35) As an example, for patients with suspected sepsis then blood cultures should always be taken. In the prior art these are transported to the microbiology lab, either at the hospital that the patient is admitted to or to the closest laboratory with microbiology facilities. The time to corrective treatment is very important and it has been shown that mortality increases 7% per hour if not proper treatment is administered. Identifying the causative organism by blood culture enables more focused antibiotics to be used, reducing complications and the risk of emerging antibiotic resistance. Each hour of delay in antibiotic administration increases the risk of deathdelay also leads to longer hospital stays and thus greater cost.
(36) The plots of
(37) From this data it is evident that the provision of culturing during transportation is hugely beneficial both for samples transported within a hospital as well as between hospitals (hub) for systems that normally require pre-culturing. Examples of such systems are as described in WO2015/189390 as well as other systems today relying on so called positive blood culture flasks and such as e.g. Nanosphere Verigen, (Nanosphere Inc.), Biofire BCID (Biomerieux), and AST/ID from Accelerate Diagnostics as described in e.g. US20150225762. The proposed methods and devices will also shorten time to so called positivity also in so called blood culture cabinets such as e.g. Biomerieux BacTec, Becton Dickinson BactAlert and Thermo Fisher VersaTrek (and similar) as long as the bacterial growth is detected using an absolute measurement and not delta growth after insertion in the system. On average a 5 hour reduction in the time to answer can be achieved within a hospital and a 16 hour reduction in time to answer is possible if samples are shipped between hospitals for systems relying on positive blood culture flasks.
(38) An important aspect for a solution to contribute to faster time-to-action is to streamline workflow. Therefore deposition of the sampled blood culture flasks from the patient at the site of routine transportation to the microbiology lab is crucial. To ensure pre-culturing the incubator then must be transportable and should be capable of both heating and agitating the medical sample during transport.
(39) As shown in the examples of