WO2016150577A1

WO2016150577A1 - Detector module

Info

Publication number: WO2016150577A1
Application number: PCT/EP2016/025029
Authority: WO
Inventors: Joachim BOLLE
Original assignee: Qiagen Lake Constance Gmbh
Priority date: 2015-03-23
Filing date: 2016-03-23
Publication date: 2016-09-29

Abstract

The invention provides for a detector module for detecting light scattered by a specimen contained in a sample. The detector module comprises a photosensitive area, and a blind partly vignetting the photosensitive area.

Description

Detector module

Field of the invention

The present invention relates to a detector module for de^¬ tecting scattered light and a method for optical measuring using such a detector module.

Description of the related art

In optical measuring methods a specimen to be examined is irradiated by an excitation beam emitted by a source, the beam scattered by the specimen in response to the excita^¬ tion beam is detected and evaluated by a detector. During irradiation the specimen can be contained in different samples. One known sample is a so called lateral flow test strip used in lateral flow tests.

Further possible samples comprise Thin Layer Chromatography (TLC) , gel electrophoresis, liqid films/hydogels, radiomet^¬ ric reference standards (grey cards) , and electrochroma- tography .

Lateral flow tests as an example for an optical measurement technique have become invaluable tools for various diagnos^¬ tics applications in the past. Among the most prominent reasons for this development are that these tools demon^¬ strate reasonable, in some cases even excellent, e. g. en^¬ zyme linked immunosorbent assays, sensitivity and specific^¬ ity for many applications and provide fast time to result since they are applied to the sample directly often without the need of prior time-consuming sample preparation steps. Lateral Flow Tests, e. g. immunoassays, are easy to operate and can be read out by simple hand-held detection devices and therefore, they are cheap and mobile.

Devices used for lateral flow tests are intended to detect the presence or absence of a target analyte in a sample without the need for specialized and costly equipment. Typically, these tests are used for medical diagnostics.

Other fields of application are food and feed analysis, point-of-need testing, point-of-care testing etc.

Detectors for optical read out of lateral flow test strips are known. These detectors convert the detected optical signal into electronic signals. In methods according to the state of the art using a confocal measuring system light from an LED is collimated by a lens and directed onto a beam splitter. The beam splitter reflects the light through another lens and a reflecting mirror on a test strip. The scattered light from the test strip falls on the deflecting mirror, the lens, the beam splitter, a further deflecting mirror via a further lens to the photo diode.

When using lateral flow test strips it has to be considered that the excitation light beam has to form a rectangular shape on the test strip. Furthermore, signal strength of the detector is maximum in the specified working distance. The signal strength falls sharply outside the working dis^¬ tance. This causes a problem when reading from flat surfaces which exhibit uneveness or are not being positioned exactly within the working distance as it often is the case with lateral flow devices handled manually in non- laboratory settings. Using a confocal arrangement for measuring requires the use of additional pinholes that makes the arrangement complex and expensive. Not using a confocal arrangement makes the measuring highly dependent on the distance between sample and detector.

This represents a challenge for quantitative measurements on Lateral Flow Strips by virtue of the uneveness of the surface and inconsistant height adaption due to manual han^¬ dling issues.

Known optical detectors require a variety of optical compo^¬ nents leading to increased costs.

Summary of the invention

In contrast thereto, the invention proposes a detector mod^¬ ule for detecting light scattered by a specimen contained in a sample, comprising a photosensitive area for capturing the beam emitted by the specimen, and a blind partly vi^¬ gnetting the photosensitive area and arranged such that the rate or degree of vignetting or shadowing is typically at least in a working range of the detector module, e. g. +- 3 mm, dependent on the distance between the specimen and the blind. Therefore, the blind causes the beam in the detec^¬ tion channel to the photosensitive area to be partly shaded. The detector uses a non-confocal measuring arrange^¬ ment .

According to an embodiment the blind is formed by an aper^¬ ture partly covered by a bar intransparent for the beam emitted by the specimen. This bar is arranged such that the extent or rate of vignetting the photosensitive area is de^¬ pendent on the distance between the specimen emitting the beam to be detected and the blind leading to an almost con^¬ stant signal strength within a certain distance range.

Furthermore, the photosensitive area can comprise a photo- diode. This photodiode transforms the captured beam or light into an electrical or electronic signal representing the beam. Alternatively, a photomultiplier or an avalanche diode can be used.

In an embodiment the detector module further comprises a source for providing at least one electromagnetic beam in^¬ tended to irradiate the sample and to interact with the specimen within the sample. Therefore, the source and the photosensitive area are integrated in one module and typi^¬ cally enclosed in one housing.

According to an embodiment the source is a light-emitting diode (LED) .

Moreover, the detector module can be adapted for performing a non-confocal measurement.

In a further embodiment at least one aperture for shaping the beam emitted by the source is provided. Here, two aper^¬ tures can be provided giving the beam emitted by the speci^¬ men a rectangular shape so that the beam spot on the sample caused by the beam is rectangular in shape.

Moreover, the detector can be adapted for detecting a beam emitted by a specimen contained within a lateral flow strip .

Furthermore, a method for detecting light scattered by a specimen using a detector module as described above is pro^¬ posed . The specimen can be contained within a lateral flow strip. The detector can detect a scattered beam emitted by the specimen. Furthermore, the specimen can be contained within a liquid, a liquid film, a liquid gel, a chromatographic layer, an immuno absorbent layer, a polymer, or within or on top of a solid substrate.

During measurement the sample or test strip pattern can be scanned laterally at varying distances with minimal or no losses of signal intensity.

Furthermore, a measuring arrangement using such a detector module is proposed. This arrangement comprises a detector module and a source suitable for performing a method as de^¬ scribed above. The detector module and the source can be integrated in one housing forming one device. The source and the detector are arranged such that a non confocal measurement is performed.

The proposed solution allows for reducing the number of op^¬ tical elements. The method can be carried out only with a light source, a photodiode, and blinds. The used arrange^¬ ment is typically not confocal but operates at an angle. A beam splitter is not required. However, a special blind forming an aperture is used in the detection channel which partly covers the photodiode at the predetermined distance range of the sample, e.g. the test strip. This blind is suitable for shadowing or vignetting the photodiode keeping the signal level of the photodiode constant, almost inde^¬ pendent from the distance between specimen and photodiode.

A feature of the invention is the special blind which is mounted in front of the detection channel. This blind en^¬ sures that within a predetermined distance range between the sample, in the following called test strip, and the de^¬ tector, the signal from the photodiode is almost independ^¬ ent of distance.

This can be achieved under the following conditions: The excitation light beam, here around 520 nm, it can also be a different wavelength, or white light, passes for beam shap^¬ ing through two slit apertures perpendicular to the test strip. Regardless of distance, the test strip is thus illu^¬ minated at the same location. The detection channel, in the test set-up at 25 ° to the excitation channel, but another angle could also be selected, has its point of intersection with the excitation channel 11 mm in front of the detector. However, a different value could also be selected. The di^¬ ameter of the detection channel is 4 mm. At the end of the detection channel the photodiode is mounted. The light- sensitive surface is 3 mm x 3 mm.

Situation without this special blind: By variation of the distance between detector and test strip, the light scat^¬ tered back from the illuminated area of the test strip falls through the aperture (restricted by the 4 mm diameter of the detection channel) onto the photodiode. When the test strip is closer to the detector, a stronger signal is measured by the photodiode than if the test strip is far^¬ ther away due to Lambertian scattering.

This behavior is modified by the special blind in the aper^¬ ture of the detection channel as follows: If test strip is closer to the detector, part of the scattered light from the test strip is shielded by the special blind in the ap^¬ erture of the detection channel. This results in a lower value of the signal generated by the photosensitive area, e.g. the photodiode signal, than without the special blind. When the sample or test strip is moved away from the detec- tor, scattered light is less shielded. So, variation in signal intensity due to varying distance between the test strip and the detector is compensated by virtue of the spe^¬ cial blind. Consequently, the photodiode signal is almost independent of test strip to detector distance.

For the arrangement described above, the design of the spe^¬ cial blind is optimized (25 ° - angle between excitation and detection light channel, 11 mm intersection in front of the detector, 4 mm diameter of light channel, and 3 mm x 3 mm light-sensitive photodiode area) . It is to be considered that the position and the width of the aperture are criti^¬ cal parameters which must be determined to allow correct design of the detector.

During irradiation the specimen can be contained in different samples. One known sample is a so called lateral flow test strip used in lateral flow tests. Further possible samples comprise Thin Layer Chromatography (TLC) , gel elec^¬ trophoresis, liqid films/hydogels , radiometric reference standards (grey cards) , and electrochromatography, but is not restricted to these.

Typically, the tests described herein are used for medical diagnostics. Other fields of application are food and feed analysis, point-of-need testing, point-of-care testing etc.

The detector can be implemented in an optical simulation program using macro languages. In this program, three steps can be implemented. The position, width, and spacing of the blind from the test strip can be varied within reaonable limits. At each step, ray tracing from a LED is conducted to the photodiode and determines the power on the detector surface. At the end of the program, the determined values are exported and analyzed with another program. So it can be determined whether a system satisfies the required de^¬ mands .

Further features and embodiments of the invention will be^¬ come apparent from the description and the accompanying drawings .

It will be understood that the features mentioned above and those described hereinafter can be used not only in the combination specified but also in other combinations or on their own, without departing from the scope of the present invention .

The invention is diagrammatically illustrated in the draw^¬ ings by means of an embodiment by way of example and is hereinafter explained in detail with reference to the draw^¬ ings. It is understood that the description is in no way limiting on the scope of the present invention and is merely an illustration of a preferred embodiment of the in^¬ vention .

Brief description of the Drawings

In the drawings,

Figure 1 is a detector according to the state of the art together with a graph illustrating signal strength plotted against distance,

Figure 2 is a detector according to the state of the art in top view and side view,

Figure 3 is a graph illustrating signal strength plotted against distance for a detector according to figure 2,

Figure 4 is an embodiment of a detector module according to the invention, Figure 5 illustrates functionality of a blind according to the invention,

Figure 6 illustrates functionality of a blind according to the invention,

Figur 7 is a graph illustrating signal strength plotted against distance,

Figure 8 is an embodiment of a blind according to the in^¬ vention,

Figures 8a to c are further embodiments of the blind ac^¬ cording to the invention.

Figure 9 is a graph illustrating data of scan on test strip pattern and a diagram showing a test strip pattern.

Detailed Description

The figures are described cohesively and in overlapping fashion, the same reference numerals denoting identical parts .

Figure 1 shows a detector 10 for the optical measurement of a lateral flow test strip 12. The detector 10 emits an ex^¬ citation beam 14, e. g. an excitation light beam, for irradiation of the test strip 12. The test strip 12 emits opti^¬ cal signals 16 in response to the excitation beam 14. The optical signals 16 can be caused by scattering.

The detector 10 converts the optical signal 16 into elec^¬ tronic signals. The drawing shows that the excitation beam forms a rectangular shape on the test strip.

The diagram on the right side shows the sequence of signal strength 20 plotted against the distance between detector 10 and test strip 12. Within a specified working range about a working point 22 the signal strength 20 is not suf^¬ ficiently constant.

Figure 2 is a description of prior detection with a state of the art detector 30 shown in top view on the left side and in side view on the right side.

Light from a light-emitting diode (LED) 32 is collimated by a lens 34 and directed onto a beam splitter 36. The beam splitter 36 reflects the light through another lens 38 and a reflecting mirror 40 onto a test strip 42. The scattered light from the test strip 42 is collected by the reflecting mirror 40 and passes through the lens 38 , the beam split^¬ ter 36, a further reflecting mirror 44, and a focusing lens 46 onto the photodiode 48. The shown arrangement represents a confocal system.

Figure 3 shows the result of a measuremt performed with an arrangement as shown in Figure 2. The diagram shows the se^¬ quence of signal strength 60 plotted against distance be^¬ tween detector and test strip. The diagram shows that the signal strength is not constant within a working field 62.

The arrangement according to Figure 2 has a number of dis^¬ advantages. First of all, it requires a variety of optical components. Furthermore, the signal strength of the detec^¬ tor is maximum at the working distance 64 and then falls of sharply .

The detector module according to the invention has a much flatter signal response over its working distance as can be seen in Figure 3 denoted with reference numeral 66.

Figure 4 shows an arrangement or detector module 80 accord^¬ ing to the invention. In contrast to the known arrangement as shown in figure 2, all optical elements were removed for the new arrangement. The new arrangement only uses a beam or light source 82, a photodiode 84, and apertures, namely a first aperture 84 and a second aperture 86. Furthermore, the drawing shows a detection channel 90 and a test strip 92.

The arrangement is not confocal but operates at an angle. Therefore, the beam splitter is obsolete. A special blind or aperture blind 88 is used in the detection channel 90 which partly covers the photodiode 84 at the predetermined distance range of the test strip 92. The blind 88 vignettes or shadows the photodiode keeping the signal level of the photodiode 84 and therefore the detector signal constant.

It is to be noted, that the design of the blind can be op^¬ timized by an optical design program.

Figures 5 and 6 illustrate the mode of functioning of the blind. Figure 5 shows an excitation light beam 100, a tar^¬ get 102, stray light 104, a photosensitive area 106, and a blind 108. Accordingly, Figure 6 shows an excitation light beam 200, a target 202, stray light 204, a photosensitive area 206, and a blind 208. Each blind 108 and 208 comprises an aperture 112 or 212 partly covered by a bar 114 or 214.

Double arrow 110 in Figure 5 and double arrow 210 in Figure 6 represent the distance between target 102 or 202 and de^¬ tector housing.

Figures 5 and 6 illustrate that the blinds 108 and 208 are arranged and designed such that the rate or extent of shad^¬ owing the photodiode 106 or 206 is dependent on the dis^¬ tance 110 or 210. The greater the distance is the less the influence of the blind 108 or 208 is. The amount of stray light 104 or 204 not transmitted to the photodiode 106 or 206 determines the rate of shadowing. The smaller the dis^¬ tance is the greater is the amount of stray light not transmitted to the photodiode 106 or 206 and therefore, the rate of shadowing or vignetting. Therefore, the amount of stray light not transmitted to the photodiode 106 or 208 depends on the distance. As the dis^¬ tance as well determines the amount of stray light reaching the blinds 108 or 208, the amount of stray light captured by the photodiode 106 or 206 is nearly constant and not de^¬ pendent on the distance 110 or 210.

Figure 7 shows detector signals plotted against distance. A first sequence 230 shows a detector signal which is not constant in relation to the distance. This is a detector signal obtained by an arrangement according to the present invention with a circular aperture 252 but without a sec^¬ tion or bar 254.

A second sequence 232 shows a detector signal using a de^¬ tector module according to the present invention which is nearly constant within a working distance range 234.

Figure 8 show an embodiment of the blind used in a detector module according to the invention denoted with reference number 250. The blind 250 comprises a circular aperture 252 which is partly covered by a section or bar 254 made of a material which is intransparent or at least semitransparent for a beam emitted by a specimen. The blind 250 is arranged in front or within a detection channel of a detector module according to the invention. The section can be of any suitable shape, as can be seen in Figures 8a to 8c showing blinds 260, 270, and 280 having apertures 262, 272, and 282 and sections 264 274, and 284. Especially the bar 284 shown in Figure 8c having a asymmetric shape proved to produce good results.

Figur 9 shows the graph of the measured data of a scan on a test strip pattern which is shown on the right side and de^¬ noted with reference number 300. The test strip pattern 300 is scanned laterally at varying distance and comprises a first black area 302, a second black area 304 and a grey area 306.

The two black areas 302 and 304 and the grey area 306 are clearly visible represented by the signal troughs 312, 314 and 316 in the 3D data plot on the left side, the deeper the trough, the higher the absorbance of light by the sam^¬ ple. In the range between 6 mm and 12 mm between the detec^¬ tor and the test strip, the measurement signal is very con^¬ sistent for the grey and black areas 302, 304 and 306 shown by the flatness of the bottoms of the troughs 312, 314 and 316 in the 3D plot distance 320 axis.

Claims

1. Detector module for detecting light scattered by a specimen contained in a sample, comprising a photosensitive area for capturing the beam emitted by the specimen, and a blind partly vignetting the photosensitive area and ar^¬ ranged such that the rate of vignetting is dependent on the distance between the specimen and the blind.

2. Detector module according to claim 1, wherein the blind is formed by an aperture partly covered by a section intransparent for the beam emitted by the specimen.

3. Detector module according to claim 2, wherein the section is a bar.

4. Detector module according to one of claims 1 to 3, wherein the photosensitive area comprises a photodiode.

5. Detector module according to one of claims 1 to 4, wherein the detector module further comprises a source for providing at least one electromagnetic beam intended to ir^¬ radiate the sample and to interact with the specimen within the sample.

6. Detector module according to claim 5, wherein the source is a light-emitting diode (LED) .

7. Detector module according to claim 5 or 6, which is adapted for performing a non confocal measurement.

8. Detector module according to one of claims 5 to 7, wherein at least one aperture for shaping the beam emitted by the source is provided.

9. Detector module according to claim 8, wherein two apertures are provided giving the beam emitted by the speci^¬ men a rectangular shape.

10. Detector module according to one of claims 1 to 9, wherein the detector is adapted for detecting a beam emitted by a specimen contained within a lateral flow strip.

11. Method for detecting a beam emitted by a specimen using a detector module according to one of claims 1 to 10.

12. Method according to claim 11, wherein the specimen is contained within a lateral flow strip.

13. Method according to claim 11 or 12, wherein the detector detects a scattered beam emitted by the specimen.