Abstract:
A miniaturized sensor ( 100 ) that improves the confidence measure of a given sample reading by directing the flow of sample to the sensor/sample interface ( 117 ) and thus bringing the sample reliably in contact with the sensor&#39;s biosensing film. An inlet flow channel ( 105 ) extending from the bottom ( 125 ) of the sensor ( 100 ) to the sensing surface ( 120 ). The inlet channel ( 105 ) guides the sample to a cavity 115 formed at a housing surface ( 120 ) where it interacts with the film deposit ( 117 ). An outlet channel ( 110 ) extends from the cavity ( 115 ) to the bottom surface ( 125 ) and directs the sample outside the device. The light source ( 58 ), detector array ( 68 ) and interface ( 54 ) can be added to the structure providing a fully integrated miniaturized sensor. Various well known methods of manufacturing may be used including mill casting, split molding and double mold processes.

Description:
This application claims priority under 35 USC § 119(e)(1) of provisional application Ser. No. 60/036,150 filed Jan. 22, 1997, abandoned. 
    
    
     TECHNICAL FIELD 
     The present invention relates in general to the field of optic based sensors and more specifically to a miniaturized sensor platform with integrated flow channels for directing the sample analyte of interest uniformly over the sensor/sample interface. 
     BACKGROUND OF THE INVENTION 
     Without limiting the scope of the invention, its background is described in connection with the Surface Plasmon Resonance (“SPR”) phenomenon in connection with miniaturized optical sensors. It should be understood that the principles disclosed may be applied to various sensor configurations including light transmissive, fluorescence-based and critical angle among others. 
     Optical sensor systems have been developed and used in the fields of chemical, biochemical, biological or biomedical analysis, process control, pollution detection and control and other areas. With SPR-based optical sensors, a resonance is observed when a polarized beam of monochromatic light is totally internally reflected from a dielectric surface having a thin metal film formed thereon. The light internally reflected at the surface has a minimum intensity at a particular angle referred to as the resonant angle. This angle is determined by the dielectric conditions adjacent the metal film and the properties of the film itself. The interface between the sensor surface and the sample of interest shall be referred to as the “sensor/sample interface.” 
     Recent advances in light emitting components and detectors units have allowed the design of small, lightweight, fully integrated sensors. Such sensors can measure less than a few centimeters in length and are easily transported and used near the sample of interest. In addition, since most of the sensor components are readily available their overall cost of manufacturing is low. 
     While miniaturized sensors are becoming available for use in a wide range of field applications, their effectiveness as an analytical tool is largely determined by the properties of the sample analyte of interest. Fluctuations in sample concentration, temperature and other environmental conditions effect the reactive properties of film deposit in the presence of the sample. Ideally, a controlled amount of the sample with uniform properties is brought in contact with the sensor/sample interface during the sampling process. With larger systems, a flow cell may be used to control the flow rate of the sample. However, there is no equivalent control mechanism for the miniaturized optical sensors. 
     Accordingly, a device configuration that channels a uniform quantity of the sample analyte of interest across the reactive film deposit of sensor&#39;s sampling surface would ensure a more confident analysis. 
     SUMMARY OF THE INVENTION 
     The present invention discloses a miniaturized sensor platform with integrated channels for controlling the flow of sample over the sensor/sample interface. 
     A primary object of the present invention is to provide a miniaturized integrated sensor capable of use in optically guided sensing applications. The sensor package of the present invention integrates a light source, detector means, light guide optics and a simplified system interface into a compact miniaturized package. Flow channels are molded inside the sensor housing and extend to an area along the sensor sampling surface. In one embodiment, an inlet channel guides the sample into the housing from the outside where it collects in a cavity topped by a portion of the biosensing film. A constant flow of pressure is provided to move the sample via an outlet channel to the outside. 
     Another object of the present invention is to provide a biosensor configuration that can be inserted into a hand held instrument for practical field use. The instrument provides an opening where the sample to be tested is poured, collected and directed towards the sensor. Function buttons control the instrument&#39;s operation and a display may be provided for on-the-spot analysis. This may be particularly advantageous where a preliminary diagnosis of sample properties is required prior to more thorough analysis at a larger facility. In this regard, the instrument can be equipped with a storage compartment or the sample poured into a container for transport. 
     Disclosed in one embodiment of the invention, is a miniaturized sensor package that improves the confidence measure of given sample reading by directing the flow of sample uniformly over the biosensing film of the sensor. An inlet channel is provided with an opening at a sensor surface that guides the sample to a cavity carved out along the sampling surface interface. An outlet channel directs the sample of interest outside the device. The light source, detector array and interface form part of the sensor providing a fully integrated device. Various well known methods of manufacturing may be used including mill casting, split molding and double mold processes. 
     For a more complete understanding of the present invention, including its features and advantages, reference is now made to the following detailed description, taken in conjunction with the accompanying drawings. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     In the drawings: 
     FIG. 1 depicts a prior art SPR miniaturized sensor package; 
     FIG. 2 is a perspective view of a flow channel sensor according to one embodiment of the invention; 
     FIG. 3 shows an expanded view of the flow cavity and cavity cap used in one embodiment of the present invention; 
     FIGS. 4 a  and  4   b  depict two sides of a flow channel sensor according to one embodiment of the invention; and 
     FIG. 5 shows use of a flow channel sensor in a hand held instrument application. 
    
    
     Corresponding numerals and symbols in the different figures refer to corresponding parts unless otherwise indicated. 
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     In FIG. 1 an integrally formed optically based Surface Plasmon Resonance (“SPR”) sensor  50  is shown in close proximity to a sample  25  analyte of interest which can be a liquid or gas. The sample may be any (bio)chemical substance for which an indicator interaction is known and which can be formed into a thin biosensing layer  61 . The film is deposited on a surface  63  of the sensor and exposed to the sample  25  during analysis. Various ways of bringing the sample  25  in contact with the surface  63  may be employed such as by dipping, dropping or by using a flow cell. 
     As shown, a substrate  52  forms a device platform to which a light transmissive housing  56  is coupled. The housing material can be plastic, glass or other similar optic coupling substance. A light source is preferably located above or within the substrate  52  and has an aperture  58  there over allowing light to pass. In one embodiment, the light source is a single high intensity light emitting diode. A polarizer  62  is located near the aperture  58  to polarize passing light which, in turn, continues through housing  56  and strikes a SPR layer  64  which is preferably formed on an exterior surface of the housing  56 . 
     The SPR layer  64  may be deposited directly or placed on a glass slide or the like. This configuration achieves an optical surface phenomenon that can be observed when the polarized light is totally internally reflected from the interface between the layer  64  and the sample of interest. This principle is well understood by those skilled in the art and discussed by Ralph C. Jorgensen, Chuck Jung, Sinclair S. Yee, and Lloyd W. Burgess, in their article entitled  Multi - wavelength surface plasmon resonance as an optical sensor for characterizing the complex refractive indices of chemical samples , Sensors and Actuators B, 13-14, pp. 721-722, 1993. 
     Analysis is permitted by using a mirrored surface  66  which directs the reflected light onto a detector array  68 . The detector array  68 , in turn, senses illumination intensity of the reflected light rays. For optical radiation, a suitable photodetector array  68  is the TSL213, TSL401, and TSL1401, with a linear array of resolution n×1 consisting of n discrete photo sensing areas, or pixels. In the detector array  68 , light energy striking a pixel generates electron-hole pairs in the region under the pixel. The field generated by the bias on the pixel causes the electrons to collect in the element while the holes are swept into the substrate. 
     Each sensing area in the photodetector array  68  thereby produces a signal on an output with a voltage that is proportional to the intensity of the radiation striking the photodetector  68 . This intensity and its corresponding voltage are at their maxima in the total internal reflection region. Electrical connections  54  are coupled to one end of the substrate  52  and provides a signal pathway from the detector  68  output to the external world. 
     FIG. 1 illustrates a sensing approach wherein the sample  25  is brought in contact  30  with the SPR layer  64  for analysis. This arrangement, however, may lead to unreliable results since analysis is influenced primarily by the properties of the sample  25 . For instance, the sample concentration may vary throughout the sample mass or with time. Likewise, movement of the sensor  50  during analysis changes the orientation of layer  64  with respect to the sample  25 . This is especially true in portable hand held applications where the sensor  50  is brought to the sample. 
     Turning now to FIG. 2, an improved sensor configuration according to the invention is shown and denoted generally as  100 . Sensor  100  is similar to sensor  50  in most respects, but differs primarily by the integrally formed flow channels  105  and  110  inside the housing structure  56 . As shown, the channels  105 ,  110  extend inside the housing  56  from a first surface  120  to a second surface  125  and pierce the platform  52  to the outside. This permits the sample to flow inside the sensor housing  56  through channel  105  and enter the cavity  115  via the opening  107 . The sample flows over the metal film  117  which is deposited by known means on the bottom surface of the cavity  115 . 
     The process of directing the sample over the sensor/sample interface is illustrated in FIG.  3 . According to one embodiment, the chemical reagent  117  is deposited at the bottom of the cavity  115  to form the sensor/sample interface. In this configuration, flow channel  105  acts as an inlet passageway inside the housing  56  and directs the sample (not shown) from the bottom surface  125  of the sensor  100  to the cavity  115 . The sample collects inside the cavity  115  and flows over the sensor/sample interface  117  and is directed to opening  112  through channel  110  and outside the sensor  100 . In this way, the sample is guided in contact with the sensor/sample interface  117 . 
     FIG. 3 also shows a cavity cap  130  which completes the sample passageway formed by channels  105 ,  110  and cavity  115  by sealing the open area of the cavity  115 . In one preferred embodiment, cap  130  is a band-aid like structure that covers the top of the cavity  115 . A nonreactive material  134 , such as a teflon, coats a portion of the cap that lies directly above the open cavity. The material  134  is surrounded by a metal layer  132  to complete the cap. In one embodiment, the metal layer  132  is a piece of aluminum tape, although other similar materials may be used. 
     Accordingly, the present invention provides a sensor configuration that reliably directs a sample over a sensors&#39; sampling surface. It should be understood, however, that other miniaturized sensor configurations may benefit from the principles of the present invention. These include critical angle, light transmission and fluorescence-based sensors as well as others known to those skilled in the art. 
     While flow channels  105  and  110  are shown extending from bottom surface  125  to surface  120  according to one possible sensor configuration  100 , it should be understood that other similar arrangements of the flow channels  105 ,  110  may be achieved without departing from the true scope and spirit of the invention. For example, the flow channels  105 ,  110  may extend from other surfaces of the sensor  100  such as surfaces  130  or  135 . Also, multiple flow channel and cavity configurations may be employed. Other suitable configurations will be apparent to those skilled in the art upon reference to this disclosure and it is intended that such uses be covered by the invention. 
     Turning now to FIG. 4 a , a side profile view of the housing  56  is shown. The flow channels  105 ,  110  extend from cavity  115  to bottom surface  125 . Channel  105  has openings  107  and  109  at opposite ends which define a fluidic inlet passageway from outside the sensor  100  to cavity  115 . Likewise, channel  110  has openings  112  and  114  which provide a fluidic passageway for transporting the sample from the cavity  115  to the outside world. 
     FIG. 4 b  shows a front view of the sensing surface  120  and cavity  115  with openings  107  and  112  slightly off center about line  127 . Thus a major portion of the area defined by the cavity  115  is filled with the sample of interest which first enters the cavity  115  through opening  107  and exits the cavity  115  through opening  112 . 
     Turning now to FIG. 5, the improved sensor  100  is shown in use in a hand held instrument  150 . A sample dispenser  200  is used to place the particular sample of interest  205  into a receptor  155  of the instrument  150 . Other methods and means of introducing the sample  205  to the instrument  150  are contemplated. 
     In one embodiment, the receptor is open (not shown in this perspective) at end  160 . This allows the sample to be gravity guided to the sensor  100 . Alternatively, a pressure or vacuum means can be provided inside the instrument  150  to direct the sample to the sensor  100 . 
     As shown, instrument  150  has a base  165  which houses the sensor  100  inside. In some contemplated applications, the sensor is removed and inserted into a fitted mount or socket inside the instrument  150 . Passage  175  is utilized to bring the sample  205  to the sensor  100  while passage  180  removes it providing a flow of sample  205  for analysis. The flow of the sample  205  and other instrument functions may be controlled with keys  185 . 
     In one contemplated use of the instrument  150 , the sensor  100  is placed inside the instrument prior to use. The sample  205  is then introduced into the instrument  150  and analysis of the sensor is performed according to well known methods. After analysis, the sensor  100  can be removed, replaced or disposed. 
     While this invention has been described in reference to illustrative embodiments, this description is not intended to be construed in a limiting sense. Various modifications and combinations of the illustrative embodiments, as well as other embodiments of the invention, will be apparent to persons skilled in the art upon reference to the description. It is therefore intended that the appended claims encompass any such modifications or embodiments.