Microfluidic detection system and a microfluidic cartridge

Abstract

A microfluidic cartridge includes first and second sides and at least one flow channel and an inlet to the flow channel(s) for feeding a liquid sample, the flow channel(s) include a plurality of first optical detection sites. A detector assembly includes a slot for inserting the microfluidic cartridge and a first fixed light source with a beam path and an optical reader for reading out optical signals from at least one of the first optical detection site(s). When the microfluidic cartridge is inserted to a first predetermined position into the slot, one of the first optical detection sites of the microfluidic cartridge is positioned in the beam path of the first light source, and when the cartridge is inserted to a second predetermined position into the slot, another one of the first optical detection sites of the microfluidic cartridge is positioned in the beam path of the first light source.

Claims

1. A microfluidic detection system comprising a microfluidic cartridge and a detector assembly, the microfluidic cartridge comprises a first and a second side and at least one flow channel and an inlet to the at least one flow channel for feeding a liquid sample, the at least one flow channel comprises a plurality of first optical detection sites, and the detector assembly comprises a slot for inserting the microfluidic cartridge and a first fixed light source with a beam path and an optical reader for reading out optical signals from at least one of said first optical detection sites, said detector assembly and the microfluidic cartridge are constructed such that when the microfluidic cartridge is inserted to a first predetermined position into said slot, one of said first optical detection sites of the microfluidic cartridge is positioned in the beam path of the first light source, and when the cartridge is inserted to a second predetermined position into said slot, another one of the first optical detection sites of the microfluidic cartridge is positioned in the beam path of the first light source, wherein each of said first and said second predetermined positions of said microfluidic cartridge into said slot are determined by projecting flanges arranged on the microfluidic cartridge and cavities arranged on the detector assembly at selected positions or projecting flanges arranged on the detector assembly and cavities arranged on the microfluidic cartridge at the selected positions, which engage or snap into place to temporarily position the microfluidic cartridge in the detector assembly at one of the first and the second predetermined positions, said projecting flanges and cavities comprises a first set of projecting flanges and cavities which correspond to the first predetermined position and said projecting flanges and cavities comprises a second set of projecting flanges and cavities which correspond to the second predetermined position.

2. The microfluidic detection system of claim 1, wherein said first light source comprises a multicolor light emitting diode (LED) configured for emitting a plurality of different light beams having different wavelengths and a circuitry for switching said plurality of different light beams on and off.

3. The microfluidic detection system of claim 1, wherein the slot of the detector assembly and the microfluidic cartridge are constructed such that when said microfluidic cartridge is inserted to a predetermined position into said slot, one of the first optical detection sites of the microfluidic cartridge is positioned in the beam path of the first light source, the predetermined position of said microfluidic cartridge into said slot is determined by a click arrangement holding the microfluidic cartridge in a temporally fixed position.

4. The microfluidic detection system of claim 1, wherein the optical reader is arranged for reading out at least one of an absorption property, a reflection property or an emitting property from a liquid sample in at least one of said first detection sites when said cartridge is inserted into said slot of said detector assembly.

5. The microfluidic detection system of claim 1, wherein the optical reader is a digital imaging reader.

6. The microfluidic detection system of claim 1, wherein the optical reader comprises a charge-coupled device (CCD) reader.

7. The microfluidic detection system of claim 1, wherein the circuitry of said first light source is configured for switching said plurality of different light beams on and off independently of each other.

8. The microfluidic detection system of claim 1, wherein the detector assembly is programmed to switch the plurality of different light beams on and off such that only one of the different light beams is switched on at a time.

9. The microfluidic detection system of claim 1, wherein the plurality of different light beams comprise from 2 to 5 different light beams.

10. The microfluidic detection system of claim 1, wherein each of the plurality of different light beams independently of each other have a spectral width of up to about 50 nm.

11. The microfluidic detection system of claim 1, wherein said plurality of different light beams of said multicolor-LED are monochromatic light beams.

12. The microfluidic detection system of claim 1, wherein said plurality of different light beams of said multicolor-LED comprise at least one of a light beam having a center wavelength of about 575 nm to about 625 nm or a light beam having a center wavelength of about 425 nm to about 475 nm.

13. The microfluidic detection system of claim 1, wherein said plurality of different light beams of said multicolor-LED comprise at least three monochromatic light beams selected from red, orange, yellow, green or blue light beams.

14. The microfluidic detection system of claim 1, wherein said at least one flow channel of said microfluidic cartridge comprises a plurality of additional optical detection sites, and the detector assembly comprises at a plurality of additional fixed light source with respective beam paths, the slot of the detector is shaped such that when said microfluidic cartridge is inserted into said slot, the plurality of additional optical detection sites of the microfluidic cartridge are positioned in respective beam paths of the plurality of additional light sources, each of said plurality of additional light sources comprises a multicolor light emitting diode (LED) configured for emitting a plurality of different light beams having different wavelengths and a circuitry for switching said plurality of different light beams on and off, said optical reader is configured for reading out optical signals from said additional optical detection sites and said detector assembly comprises at least one additional optical reader configured for reading out optical signals from said additional optical detection sites.

15. The microfluidic detection system of claim 1, wherein said detector assembly comprises a light tunnel for one or more of the fixed light sources to prevent the beams from the respective fixed light sources to transmit light to two or more detection sites simultaneously.

16. The microfluidic detection system of claim 1, wherein said at least one flow channel of said microfluidic cartridge comprises a plurality of detection cites for performing a plurality of different assays.

17. The microfluidic detection system of claim 16, wherein the plurality of detection sites comprise at least one electrical detection site, said electrical detection site comprises electrodes arranged for performing an electrochemical detection at the electrical detection site, said electrodes comprise electrical wires connected to microfluidic cartridge connection pads, the detector assembly comprises at least one electrical reader for reading out electrical signals out from the electrical detection sites.

18. The microfluidic detection system of claim 17, wherein the electrical reader comprises a voltmeter electrically connected to voltmeter connection pads arranged in the slit such that the microfluidic cartridge connection pads are in electrical connection with said voltmeter connection pads when said microfluidic cartridge is inserted into said slot.

19. The microfluidic detection system of claim 1, wherein said detector assembly comprises at least one output interface and a processor, said microfluidic cartridge comprises a machine readable code comprising instructions about assays to be performed using the cartridge and said detector assembly comprises a code reader for reading the machine readable code and feeding the instructions about the assays to be performed to the processor, wherein the processor is programmed to control at least one of the readers and the output interface at least partly based on instructions obtained from the machine readable code, preferably said at least one reader is at least one of the optical reader and the electrical reader.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) The invention will be explained more fully below in connection with a preferred embodiment and with reference to the drawings in which:

(2) FIG. 1 shows a detector assembly according to the invention,

(3) FIG. 2 shows a microfluidic cartridge according to the invention,

(4) FIG. 3 shows the microfluidic cartridge in a side view,

(5) FIG. 4 shows an alternative embodiment of the microfluidic cartridge,

(6) FIG. 5 shows yet another embodiment of the microfluidic cartridge,

(7) FIG. 6 shows detection with LED and CCD,

(8) FIG. 7 shows alternative detection with LED and CCD,

(9) FIG. 8 shows detection with spectrometer,

(10) FIG. 9 shows electrical detection,

(11) FIG. 10 shows a light tunnel, and

(12) FIG. 11 shows a microfluidic cartridge adapted for electrical detection.

(13) The figures are schematic and only intended to show the principles of the invention and may be simplified for clarity. Throughout, the same reference numerals are used for identical or corresponding parts.

(14) Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

(15) The invention is defined by the features of the independent claim(s). Preferred embodiments are defined in the dependent claims. Any reference numerals in the claims are intended to be non-limiting for their scope.

(16) Some preferred embodiments have been shown in the foregoing, but it should be stressed that the invention is not limited to these, but may be embodied in other ways within the subject-matter defined in the following claims.

(17) FIG. 1 shows a detector assembly 1 according to the invention. The detector assembly comprises a screen 2, which is used for visually setting the detector assembly and visually display the result of measurements performed on the detector assembly 1.

(18) The detector assembly 1 comprises control buttons 3 which are used for setting and operating the detector assembly. The detector assembly also comprises means for connection with other hardware, such as a computer or printer.

(19) The detector assembly 1 also comprises a slot 4 in which a microfluidic cartridge may be inserted. The microfluidic cartridges are described in further details below. The interior of the detector assembly comprises means for keeping the microfluidic cartridge in a fixed position when the cartridge is inserted into the slot.

(20) Thus, when a microfluidic cartridge comprising a sample of interest is inserted into the slot 4 of the detector assembly 1, the detector assembly may perform measurements on the sample. The measurements may e.g. be optical measurements such photometric or colorometric measurement. It may also be measurements based on a charge-coupled device or magnetic measurements.

(21) FIG. 2 shows a microfluidic cartridge 10 suitable for use in the invention. In this embodiment, the microfluidic cartridge 10 comprises a substrate 12 with five cavities in the form of channels 11. Each channel 11 comprises an inlet 13 and a sink 14 with a not shown flexible wall section.

(22) The microfluidic cartridge 10 also comprises an indent which provides a read out section 16 for the channels 11, where the channels comprise a transparent window and where magnetic particles may be temporally immobilized using a not shown magnet.

(23) In this embodiment each channel 11 comprises temporally immobilized magnetic particles and temporally immobilized fluorophores. The microfluidic device is divided into zones comprising zone 0 which is the inlet zone, zone 1 and zone 2 which comprise temporally immobilized fluorophores and magnetic particles 17 arranged such that they do not react until they are in contact with the liquid sample, zone 3 which is the read out zone and zone 4 which is the sink zone.

(24) In an embodiment zone 1 comprises temporally immobilized fluorophores and zone 2 comprises temporally immobilized magnetic particles.

(25) In an embodiment zone 1 comprises temporally immobilized magnetic particles and zone 2 comprises temporally immobilized fluorophores.

(26) The microfluidic cartridge 10 may comprise several subzones of zone 1 and zone 2, if desired.

(27) In use a liquid sample is fed to the inlet 13, the sample is sucked into zone 1 of the channels using the flexible wall section, which will later be described in more details. Optionally the liquid sample is pulsated in zone 1 to dissolve or re-suspend the immobilized elements 17 in zone 1. Thereafter the liquid sample is drawn further into the channels 11 to zone 2 for dissolving or re-suspending the immobilized elements 17 in zone 2. After a preselected incubation time the liquid sample is drawn fully into the sinks 14. The magnetic particles are immobilized in the read out zone 3. Moreover, if desired, the liquid sample can be reintroduced into the channels 11 by using the flexible wall of the sink 14 and the immobilized magnetic particles can be flushed using the liquid sample to remove not immobilized fluorophores and other elements that could potentially provide noise.

(28) FIG. 3 shows the microfluidic cartridge 10 of FIG. 1 seen from the side. Although known microfluidic cartridges in principle could be applied in the present invention, the micro fluidic cartridge shown is particularly designed for the purpose and provides additional benefits to the present invention as described herein.

(29) The microfluidic cartridge 10 comprises a substrate 12 with five cavities in the form of channels 11. The channels 11 are provided in the form of grooves covered with a foil 11a. Each channel 11 is connected with an inlet 13 and at their opposite end the channels 11 are connected with a common sink 14. The inlet 13 has the shape of a well.

(30) By pressing the flexible wall section 15 of the sink 14, the wall will be moved and air will be pressed out of the channels 11, and when the pressure is released the flexible wall section 15 will return to its initial position and a liquid sample arranged in the inlet 13 will be sucked into the channel 11 to a desired position. By further manipulating the flexible wall section the liquid sample can be drawn further into the channels 11 or it may be pulsated in the channels. Finally the flexible wall section 15 may be manipulated to collect the sample in the sink and to re-flush the sample into the channels, if desired. The flexible wall section 15 thereby provides a simple and cheap method of controlling a liquid sample in the micro fluidic device.

(31) The micro fluidic cartridge also comprises an indent which provides a read out section 16 for the channels 11. In the read out sections 16 of the channels 11, the channels comprise a transparent window and the magnetic particles can be temporally immobilized using a not shown magnet. The magnet is mounted in the detector assembly which also includes a reading for reading signals through the read section 16.

(32) FIGS. 4 and 5 show alternative embodiments of the microfluidic cartridge 20.

(33) In FIG. 4 the microfluidic cartridge 20 is seen with two channels 21, which in one end is connected with an inlet 23 and in the opposite end connected with sinks 24.

(34) Along the two channels 21 a number of chambers 27, 28 are located. Each chamber is connected with the channel and each chamber may comprise an analyte, which may react with a liquid sample which will fill the chambers when it passes from the inlet 23, through the channels 21 to the sink 24.

(35) The channels 21, the inlet 23, the sinks 24, and the chambers 27, 28 are formed as recesses in the substrate 22. The access to the channels 21, the sinks 24, and the chambers 27, 28 are closed by a foil 21a, so they are only accessible via the inlet 23.

(36) The chambers 27 and 28 are placed in pairs on each side of the channel 21. The chambers may comprise the same or different analytes. For example each pair along the channel may comprise the same analyte so the sample will be tested twice with same analyte, thereby improving the certainty of the measured results. Thus, the microfluidic cartridge 20 shown in FIG. 4 may e.g. be able to measure with twelve different analytes, i.e. the microfluidic cartridge 20 comprises twelve pairs of chambers 27, 28 located along the channels 21. The analytes may be a combination of analytes, which may be measured with different means, such as optical, electrical or magnetic means. Thus, the analytes may e.g. be immobilized magnetic particles or immobilized enzymes functioning as color-forming reactants, which will react with the liquid sample, when the sample enters the chamber.

(37) FIG. 5 shows a microfluidic cartridge 20 which substantially corresponds to the microfluidic cartridge shown in FIG. 4. However, the sinks are omitted in this particular embodiment. When a liquid sample is placed in the inlet 23 it will flow into the channels 21 and the chambers 27 and 28 by means of pressure and capillary forces.

(38) Consequently, the microfluidic cartridge comprises an inlet 23 connected with two channels 21, which are connected with pairs of chambers 27, 28 along the channels. The chambers 27 and 28 are transparent to light from a light source e.g. a multicolor-LED. As such the chambers 27 and 28 are suitable for use with optical detection means.

(39) In the following FIGS. 6 to 9 the microfluidic cartridge illustrated in FIG. 5 is used as an example of some measurements which may be performed with the microfluidic detection system according to the invention.

(40) FIG. 6 shows an optical detection system in which an LED 30 emits a substantial monochromatic light beam towards a chamber in the microfluidic cartridge 20. The light beam bases the sample in the chamber and is transformed to a light beam 32 with different wavelength. The light beam 32 is detected by the CCD detector 35 below the microfluidic cartridge 20.

(41) FIG. 7 shows another embodiment in which the microfluidic cartridge 20 receives a light beam 31 emitted from the LED 30. The light beam 31 is reflected by the sample in the chamber of the microfluidic cartridge. The reflected light is divided into light with two different wavelengths 32 and 33 which are detected by the CCD detector 35 placed on the same side of the microfluidic cartridge 20 as the LED 30.

(42) FIG. 8 shows yet another embodiment of the detection system. In this embodiment the detection system utilizes a spectrometer 36 for detection of the light reflected from the sample in a chamber of the microfluidic cartridge 20. The light beam 31 is emitted from the LED 30 and reflected by the sample held in the microfluidic cartridge 20. The reflected light is reflected as light with three different wavelengths 32, 33 and 34. The reflected light is detected by the spectrometer 36 and the resulting curve is shown in the inserted box 37.

(43) FIG. 9 illustrates an alternative embodiment of the detection system. This is a system where an array or electrodes 38 send a current through one or more of the chambers in the microfluidic cartridge 20. Due to the resistance in the sample, the detection system will be able to detect the nature of the sample.

(44) FIG. 10 illustrates the principles of a light tunnel according to the invention. The light tunnel includes three LEDs 30a, 30b and 30 c, each emitting light with a wavelength which is different from the wavelengths of the other two LEDs. The LED 30a may emit light in the range: 610<<760. The LED 30b may emit light in the range 570<<590, and finally the LED 30c may emit light in the range: 450<<500.

(45) Each LED is intended to emit light to one or more specific detection sites, and to avoid transmission of incident light to detection sites where it is not desired, the light tunnel is constructed with partition members 39 which will ensure that undesired transmission of incident light is avoided.

(46) Thus, each LED 30a, 30b and 30c is enclosed by partitions members 39, which will ensure that the light emitted from the LED only transmits light to the detection site for which the light is intended.

(47) The light tunnel makes it possible to transmit light through two or more detection sites simultaneously. As seen in the embodiment of FIG. 10, the LEDs 30a, 30b and 30c transmit light simultaneously through three different detection sites on the microfluidic cartridge 20. The resulting light beams are detected by the CCD detector 35.

(48) FIG. 11 shows an alternative embodiment of a microfluidic cartridge 40 according to the invention. The microfluidic cartridge 40 comprises an inlet 43 for introduction of a sample. The inlet 43 is connected with a channel 41 which in the opposite end is connected with a sink 44. Along the length of the channel 41 are located two detection sites 47 for optical detection and further two detection sites 48 for electrical detection.

(49) The electrical detection sites 48 may comprise electrodes which are connected with connection pads 50 by means of electrical wiring 49. The electrical wiring may be printed on the substrate 42 of the microfluidic cartridge 40.

(50) The connection pads 50 may be connected with corresponding connection pads in the detection assembly and to an electrical reader, such as a voltmeter.

(51) The figures only illustrate a limited number of embodiments according the invention, and the full scope of the invention is defined in the claims. However, it is clear that several combinations are possible and the optical detection may be combined with magnetic and/or electrical detection.