WO2009027935A2

WO2009027935A2 - Biochemical sensor cartridge

Info

Publication number: WO2009027935A2
Application number: PCT/IB2008/053453
Authority: WO
Inventors: Jeroen H. Nieuwenhuis; Eduard G. M. Pelssers; Jochem Reijndorp; Albert H. J. Immink; Marco Matters; Maria E. H. G. Meuffels
Original assignee: Koninklijke Philips Electronics N. V.
Priority date: 2007-08-31
Filing date: 2008-08-27
Publication date: 2009-03-05
Also published as: WO2009027935A9; WO2009027935A3; WO2009027935A8

Abstract

The invention relates to a (bio-)chemical sensor cartridge (100) for the examination of samples like blood or saliva, which comprises a sample collection element (e.g. a swab (120)), a sensor element (130) for sensing a parameter of interest, a sample transportation mechanism (110) for transferring the sample from the sample collection element (120) to the sensor element (130), and a connector (140) for linking the device to an external reader. The sample transportation mechanism (110) may particularly comprise a reservoir (111) with a buffer liquid that can be transferred via the sample collection element (120) to the sensor element (130). Moreover, the cartridge preferably consists of two parts (101, 102) that can reversibly be connected.

Description

BIOCHEMICAL SENSOR CARTRIDGE

The invention relates to a chemical sensor cartridge for the examination of a liquid or solid sample, particularly a biological fluid like saliva or blood.

The US 6 991 898 B2 discloses a self-contained diagnostic test device for use in the collection and detection of e.g. a biological specimen. The device comprises a detachable part with a swab for collecting a sample and a further part comprising reagents that contact a test strip and a sample on the swab after collection. The reaction of the test strip, for example a color change, can be observed by a user via a transparent window of the device.

Based on this situation it was an object of the present invention to provide alternative means for the examination of samples, particularly biological samples like blood or saliva, wherein it is desirable that these means can be produced at low costs, are easy-to-use, and allow for precise and flexible measurements.

This object is achieved by a chemical sensor cartridge according to claim 1. Preferred embodiments are disclosed in the dependent claims.

The chemical sensor cartridge according to the present invention serves for the examination of a liquid or solid sample, wherein said sample may for example be a biological substance (e.g. saliva, blood, urine or some other body fluid) or a material taken from the environment (e.g. from the soil, water, or food). The sensor cartridge comprises the following components: a) A sample collection element for picking up a sample to be examined from its place of origin. The sample collection element may for example comprise a swab for collecting body fluid, e.g. saliva from the mouth of a patient. b) A sensor element for sensing a parameter of interest of a sample to be examined. The sensor element may for example be an indicator strip like that disclosed in the US 6 991 898 B2. The parameter of interest may particularly be the presence and possibly also the quantity of a particular target substance in the sample, for example the presence of a drug in saliva. c) A sample transportation mechanism for transporting picked up sample from the sample collection element to the sensor element. The sample transportation mechanism will typically perform some mechanical or even chemical preprocessing with the picked up sample during its transportation, for example a thorough mixing of the sample with a solvent such that well-defined conditions are assumed at the sensor element. d) A connector for linking the sensor element to an external reader device for reading out sensed parameters of a sample. It should be noted in this context that the external reader device is not part of the chemical sensor cartridge, but usually a more or less expensive apparatus with elaborate means for evaluating and displaying the measurement results, while the chemical sensor cartridge is typically a disposable component. The linkage between the sensor cartridge and the external reader device via the connector may be established wirelessly, for example by radiofrequency (RF) or optical (e.g. infrared) signals, which requires compatible sender and receiver components on the sensor cartridge and the external reader device. Preferably, the linkage is established by wire, i.e. the connector comprises electrical terminals which can be contacted by the reader device to provide electrical access to the sensor cartridge. Besides for a communication of sensed parameters, the linkage via the connector can also be used to supply the sensor cartridge with power, for example an electrical supply voltage.

The described chemical sensor cartridge has the advantage to provide a connector by which it can be coupled to an external reader device. It is therefore possible to use elaborate sensing and data processing technologies, because expensive and bulky components can be disposed in the reusable reader device while consumables that come into contact with the sample are separately housed in the (disposable) sensor cartridge. Due to their coupling to an external reader, the sample examination means are not restricted to simple ones (e.g. color changes) that must immediately be observed by a user.

While the sensor cartridge might in principle be designed and used as a one-piece device, it preferably consist of a "first part" and a "second part" that can be connected to examine a picked up sample, wherein the second part comprises the sensor element and the connector. After picking up a sample, the two parts of the sensor cartridge can then be connected to put all things together that are needed for the intended examination. Optionally the sample transportation mechanism may automatically be activated by putting the first and second part of the cartridge together. Preferably, the connection between the first and second part is reversible, i.e. the parts can be connected and separated from each other as often as desired by a user. In this case, it is possible to deliverer a newly fabricated sensor cartridge with the first and second parts being connected, thus forming a self-contained and sheltered unit; during use, the two parts can then be separated, the sample can be picked up with one of them, and the examination can be started after connecting the two parts again.

In various embodiments of the of aforementioned design, the first part of the sensor cartridge may comprise the sample collection element or at least parts of the sample transportation mechanism (wherein the not comprised components are arranged on the second part). Alternatively, the first part may comprise both the sample collection element and at least parts of the sample transportation mechanism.

According to a preferred design of the sensor cartridge, the examination of a picked up sample is automatically started and performed after (e.g. manual) activation of the sample transportation mechanism. The collection of the sample and the activation of the sample transportation mechanism can then be the only manual steps that are required from a user, while the residual procedure runs automatically. This eases the application of the sensor cartridge. Furthermore, it improves the reliability of the examination results as user-to-user variations in the handling are avoided as much as possible. In connection with the above two-part design of the sensor cartridge, activation of the sample transportation mechanism may e.g. simply be achieved by connecting the first and the second part of the cartridge.

The sensor element may be or comprise any sensitive unit that is suited for sensing the parameter of interest from a sample to be tested. Preferably, the sensor element comprises an optical, magnetic, mechanical, acoustic, thermal and/or electrical microelectronic sensor element. A magnetic sensor element may particularly comprise a coil, Hall sensor, planar Hall sensor, flux gate sensor, SQUID (Superconducting Quantum Interference Device), magnetic resonance sensor, magneto -restrictive sensor, or magneto -resistive sensor of the kind described in the WO 2005/010543 Al or WO 2005/010542 A2, especially a GMR (Giant Magneto Resistance), a TMR (Tunnel Magneto Resistance), or an AMR (Anisotropic Magneto Resistance). An optical sensor element may particularly be adapted to detect variations in an output light beam that arise from a frustrated total internal reflection due to target particles at a sensing surface. Other optical, mechanical, acoustic, and thermal sensor concepts are described in the WO 93/22678, which is incorporated into the present text by reference.

In a preferred embodiment of the invention, the sample transportation mechanism comprises a reservoir for a transportation liquid like a buffer. The transportation liquid may optionally be considered as a part of the sensor cartridge (e.g. if it is already disposed in the reservoir during fabrication of the sensor cartridge) or not (e.g. if it has to be supplied to the reservoir by the user before application of the sensor cartridge). The transportation liquid serves as a medium that carries the sample to be examined (or at least the components of interest of such a sample), that allows for a well-defined transfer of sample to the sensor element, and/or that presents the sample under definite conditions (e.g. concentration, viscosity) to the sensor element.

According to a further development of the aforementioned embodiment, the reservoir is at least partially sealed by a cover, e.g. within a pouch, that can be broken to start the sample transportation. In the above two-part design of the sensor cartridge, the breaking of the cover may for example be caused by the connection of the first and the second part of the cartridge. Moreover, the start of the sample transportation may simultaneously be the start of the whole examination procedure, too.

In another modification of the sample transportation mechanism with a reservoir for a transportation liquid, a pumping device may be provided for inducing a flow of transportation liquid via the sample collection element to the sensor element. The pumping device may particularly comprise means for manually shifting the transportation liquid, for example by a syringe-like mechanism. The sensor cartridge may further optionally comprise a filter unit that is disposed in the transportation passage of the sample transportation mechanism, i.e. in the passage via which a picked up sample is transferred from the sample collection element to the sensor element. The filter unit may for example be realized by some porous material, and it may be used to retain certain materials (e.g. particles larger than a given threshold) from reaching the sensor element. Moreover, the flow of the sample fluid through a filter will usually induce a thorough mixing and thus increase the homogeneity of the fluid.

In a further development of the invention, the sensor cartridge comprises an indicator for detecting and indicating if sufficient sample has been collected on the sample collection element. This indicator may for example comprise a wetting detector that determines if the wetting grade of the sample collection element is above a given threshold value. Thus the user is provided with a feedback if the collected sample is adequate for the intended examinations. These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter. These embodiments will be described by way of example with the help of the accompanying drawings in which:

Figure 1 schematically shows a section through a biochemical sensor cartridge according to the present invention; Figure 2 shows a perspective view of a possible product design of the sensor cartridge; Figure 3 shows the insertion of the sensor cartridge of Figure 2 into an external reader; Figure 4 illustrates consecutive steps of the application of the sensor cartridge;

Figures 5 to 7 illustrate preferred arrangements of components on two parts of a sensor cartridge according to the present invention. Like reference numbers or numbers differing by integer multiples of 100 refer in the Figures to identical or similar components.

In the field of biochemical diagnostics, saliva is a difficult sample because its properties are not very well defined. For example, its mechanical properties (such as viscosity) may vary from person to person and may also depend on the time of day, whether the person to be tested has just eaten/drunk something etc. For this reason a saliva sample may favorably be diluted with a buffer to get consistent results. A problem with such a dilution is however that it requires the operator to take several steps. Additionally, most known tests require quite a large sample volume, which can easily take more than a minute to collect. In particular for point-of-care applications the long sample collection time and the complicated handling are not acceptable.

To address the above problems, a biosensor is proposed here with a disposable component that consists of only two parts. One of the parts contains a small swab, and a conditioning (buffer) liquid is also contained in one of the two parts of the disposable, so no extra parts are needed.

Figure 1 shows schematically the main components of a biochemical sensor cartridge 100 according to a first embodiment of the aforementioned approach. The sensor cartridge 100 is composed of two parts 101 and 102 that can reversibly be connected via a snap-in or "click" -mechanism (wherein the connected state is shown in Figure 1). In this embodiment, the first part 101 comprises two components:

A reservoir 111 with a buffer liquid, which establish a main component of a sample transportation mechanism 110.

A swab 120 serving as a sample collection element. The swab may consist of any natural or manmade material that is suited or known for medical swabs, particularly woven or nonwoven materials, for example cellulosic materials, synthetic polymeric nonwoven materials, polymeric foams or a combination of such. It will typically only contain a few μl of liquid, so it fills very rapidly. Just touching the tongue of a person to be tested suffices to almost instantaneously saturate the swab. This makes the sample taking as quick and comfortable as possible.

The second part 102 of the sensor cartridge 100 comprises the following components within a common housing: A sensor element 130, which may particularly be realized by a biosensor chip.

A connector 140 comprising electrical contact pads on the outside of the housing that are electrically connected to the sensor element 130. This allows transferring the results from the biosensor chip 130 to read-out electronics inside a reader 1.

A sample transportation passage through which the above buffer liquid of the reservoir 111 can flow via the swab 120 to the sensor chip 130, wherein said passage comprises a larger cavity 112 in which a capillary channel 114 leading to the sensor chip 130 ends with a capillary pick-up 113. Via the capillary channel 114, sample liquid can be transferred to the sensor chip 130 in a well-defined way. Furthermore, a venting hole 115 (Figure 1) is provided through which air can be vented when the buffer liquid enters the cavity 112.

A filter unit 150 disposed in the aforementioned sample transportation passage between the swab 120 and the cavity 112 such that the buffer liquid with the sample must flow through it before it reaches the sensor element 130. The filter 150 typically has a volume that is a few times larger than that of the swab 120. The filter has the two main functions to (i) filter out any debris that is present in the sample and (ii) additionally mix the sample and the buffer.

Figure 2 shows a possible product design of the sensor cartridge 100, wherein the two parts 101 and 102 are disconnected. Additionally to Figure 1, a press button 116 can be seen that is disposed adjacent to the buffer reservoir 111. Pressing this button will exert a pressure on the buffer liquid in the reservoir 111 and thus initiate the transfer of this liquid via the swab 120 to the sensor element 130. The form-factor of the shown device makes it easy to handle.

Figure 3 shows in a perspective view the sensor cartridge 100 in its connected state immediately before insertion into the connection slot of an external reader 1. An entire measurement procedure with the sensor cartridge 100 could be such as depicted in Figure 4:

In Figure 4 a), the disposable sensor cartridge 100 is provided in a sealed package 2 that allows for controlled storage conditions.

In Figure 4 b), the sensor cartridge 100 is inserted with the connector 140 in the reader 1.

In Figure 4 c), the first part 101 of the sensor cartridge 100 is pulled from the reader 1 and thus separated from the second part 102 which remains in the reader 1. This could be implemented by using two orthogonal mechanical movements, e.g. rotation (screw) for one interface and translation (insert and click) for the other interface.

In Figure 4 d), the first part 101 is used to collect a sample (e.g. saliva) with the exposed swab 120.

In Figure 4 e), the first part 101 with the swab is reconnected to the second part 102 in the reader 1, for example by a 'clicking' mechanism. The second part then releases the buffer from the integrated reservoir, which then flows through the swab 120 picking-up the sample. Finally the filtered and conditioned liquid reaches a stage where the sample is drawn into the capillary channel 114 (Figure 1), which transports the liquid to the biosensor chip 130 for analysis, thus starting the measurement. In this way the sample is automatically taken from the swab, conditioned and transported to the integrated biosensor chip after reconnecting the first and second parts 101 and 102. Starting the measurements could instead be achieved by another action, such as for example pressing a release button on a part of the disposable sensor cartridge. The release of buffer liquid may be implemented by piercing a pouch of buffer liquid. Furthermore, the buffer liquid can be forced out of the reservoir by decreasing the reservoir volume (via the press button 116), or it may flow due to capillary forces. In the embodiments discussed above the disposable sensor cartridge 100 consisted of two parts 101 and 102, where the buffer 111 was stored with the swab 120 in a first part 101 of the disposable and the chip 130 was stored with the electrical connector 140 in the other part. This embodiment is schematically depicted in Figure 5 (top: disconnected state; bottom: connected state). A potential drawback of this embodiment is that the buffer is contained in the same part 101 as the swab 120. By an uncontrolled release of the buffer, the person tested may get into contact with the buffer. Figure 6 shows an alternative embodiment with a mechanism to prevent the aforementioned problems from happening (top: disconnected state; bottom: connected state). In this second embodiment, a first part 201 of the disposable sensor cartridge 200 only contains the swab 220. This has the advantage that the tested person can never be exposed to the buffer liquid. However, the flow of liquid through the device is somewhat more complicated, where the buffer has to flow via a first channel 212 from the reservoir 211 to the swab 220 and then via a second channel 213 back to the second part 202 of the sensor cartridge 200.

Figure 7 shows a third embodiment of a sensor cartridge 300 (top: disconnected state; bottom: connected state), where the buffer reservoir 311 is isolated in a first part 301 of the sensor cartridge 300 (e.g. in the form of a cap that can be clicked on in a last operator step), and where all other elements are located in the second part 302. With this embodiment the tested person cannot get exposed to the buffer liquid, and the flow of buffer liquid is straightforward via channels 312 and 313 to the swab 320 and the sensor chip 330, respectively. For this embodiment it might be advantageous to first collect the sample and then to insert the disposable sensor cartridge 300 in the reader. In an alternative embodiment the disposable sensor cartridge may be inserted into the reader first and sample taking must be done with the combined device.

As an option, a sample adequacy indicator/wetting detector may be integrated in the cartridge, e.g. behind a porous medium adjacent to the swab, to assure that sufficient sample is collected and to prevent fraud.

In summary, a disposable sensor cartridge for biosensing applications has been described that consists of only two parts, comprising a reservoir with buffer liquid, a sample collection element, a sensing element, and an interface to connect the cartridge to a reader that allows for automatic read-out of the sensor, wherein only a single operator step is required (which releases the buffer) to start the measurement. The advantages of the disposable cartridge comprise: fast sample collection, almost instantaneous; few, very simple operator steps; - just two parts; well conditioned sample due to integrated buffer; robust fluidics due to integrated buffer; hygienic sealing of saliva inside the disposable. While the invention was described above with reference to particular embodiments, various modifications and extensions are possible, for example:

The sensor element can comprise any suitable sensor to detect the presence of target particles, based on any property of the particles and/or labels attached to them, e.g. it can detect via magnetic methods, optical methods (e.g. imaging, fluorescence, chemiluminescence, absorption, scattering, surface plasmon resonance, Raman, etc.), sonic detection (e.g. surface acoustic wave, bulk acoustic wave, cantilever, quartz crystal etc.), electrical detection (e.g. conduction, impedance, amperometric, redox cycling), etc.

A magnetic sensor can be any suitable sensor based on the detection of the magnetic properties of a target particle on or near to a sensor surface, e.g. a coil, magneto -resistive sensor, magneto -restrictive sensor, Hall sensor, planar Hall sensor, flux gate sensor, SQUID, magnetic resonance sensor, etc.

In addition to molecular assays, also larger moieties can be detected with sensor devices according to the invention, e.g. cells, viruses, or fractions of cells or viruses, tissue extract, etc. Other liquids than saliva can be used as well, such as blood or urine. - Measurement data can be derived as an end-point measurement, as well as by recording signals kinetically or intermittently.

The device and method can be used with several biochemical assay types, e.g. binding/unbinding assay, sandwich assay, competition assay, displacement assay, enzymatic assay, etc. It is especially suitable for DNA detection because large scale multiplexing is easily possible and different oligos can be spotted via ink-jet printing on a substrate.

The device and method can be used as rapid, robust, and easy to use point-of-care biosensors for small sample volumes.

Finally it is pointed out that in the present application the term "comprising" does not exclude other elements or steps, that "a" or "an" does not exclude a plurality, and that a single processor or other unit may fulfill the functions of several means. The invention resides in each and every novel characteristic feature and each and every combination of characteristic features. Moreover, reference signs in the claims shall not be construed as limiting their scope.

Claims

CLAIMS:

1. A chemical sensor cartridge (100-300) for the examination of a liquid or solid sample, comprising a) a sample collection element (120-320) for picking up a sample from its place of origin; b) a sensor element (130-330) for sensing a parameter of the sample; c) a sample transportation mechanism ( 110-310) for transporting sample from the sample collection element to the sensor element; d) a connector (140-340) for linking the sensor element to an external reader device (1) for reading out the sensed parameter.

2. The sensor cartridge (100-300) according to claim 1, characterized in that it comprises a first part (101-301) and a second part (102-302) that can be connected, wherein the second part comprises the sensor element (130-330) and the connector (140-340).

3. The sensor cartridge (100-300) according to claim 2, characterized in that the first part (101-301) comprises the sample collection element (120-320) and/or at least a part of the sample transportation mechanism (110- 310).

4. The sensor cartridge (100-300) according to claim 1, characterized in that the examination is automatically performed after activation of the sample transportation mechanism (110-310).

5. The sensor cartridge (100-300) according to claim 1, characterized in that the sensor element comprises a sensor element (130- 330) an optical, magnetic, mechanical, acoustic, thermal or electrical sensor element.

6. The sensor cartridge (100-300) according to claim 1, characterized in that the sample transportation mechanism (110-310) comprises a reservoir (111-311) for a transportation liquid, particularly a buffer liquid.

7. The sensor cartridge (100-300) according to claim 6, characterized in that the reservoir (111-311) is at least partially sealed by a cover that can be broken to start the sample transportation.

8. The sensor cartridge (100) according to claim 1, characterized in that the sample transportation mechanism (110) comprises a pumping device (116) for inducing a flow of transportation liquid via the sample collection element (120) to the sensor element (130).

9. The sensor cartridge (100-300) according to claim 1, characterized in that it comprises a filter unit (150) disposed in the transportation passage of the sample transportation mechanism (110).

10. The sensor cartridge (100-300) according to claim 1, characterized in that it comprises an indicator for detecting and indicating if sufficient sample has been collected.

11. A first part (101-301) according to claim 3.

12. Use of a first part (101-301) according to claim 3.