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Transducer for microfluid handling systemRelated Patent Categories: Measuring And Testing, Liquid Analysis Or Analysis Of The Suspension Of Solids In A LiquidTransducer for microfluid handling system description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070033990, Transducer for microfluid handling system. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention relates to a sensor using microscopic flexible mechanical structures such as micro-cantilevers, micro-bridges or micro-membranes integrated into microscopic chambers. In particular, the present invention relates to a sensor for measuring biochemical properties of fluids in such chambers. TECHNICAL BACKGROUND [0002] The measurement of the properties of fluids flowing in microscopic channels is of importance in the field of micro liquid handling systems, which includes systems for measuring: [0003] 1) physical properties such as flow rates viscosity and local temperature [0004] 2) chemical properties such as pH and chemical composition [0005] 3) biological properties such as identification of organic constituents in fluids, including DNA fragments, proteins, and complete biological cells [0006] Microliquid handling systems typically consist of narrow channels of order 100 microns wide and 100 microns deep engraved or embossed into the surface of a thin wafer of a material such as silicon, glass or plastic using reproduction techniques based on micromachining. The surface containing the channels is usually bonded to another surface, in order to seal the channels. Fluids pumped through the resulting channels typically flow in a completely laminar fashion. As a result, several different fluids can be flowed in laminated streams through such microsystems, without any significant mixing of the fluids. [0007] An important advantage of a microliquid handling system is that very small quantities of fluid can be directed in a controlled fashion to various parts of the system, where various analytical techniques can be used to determine the properties of the liquid. This can be done using external analytical techniques such as optical detection. The controlled flow of the fluid is achieved via pumps and valve systems that can be either external or integrated with the microchannels. [0008] Micro-cantilevers are devices where changes in the mechanical properties of a microscopic micro-cantilever are used to detect changes in the environment of the micro-cantilever. The micro-cantilever is typically of the order of 100 microns long, 10 microns wide and one micron thick. The micro-cantilevers are made of a material such as silicon, silicon nitride, glass, metal or combination of any of these, using micromachining techniques. A change in the mechanical properties can for example be a stress formation in the micro-cantilever due to changes in surface stress of the micro-cantilever. Stress formation can also occur due to changes in temperature of the micro-cantilever due to a bimorph effect, if the micro-cantilever is made of two materials with different thermal expansion coefficients. Such stress formations in the micro-cantilever can be detected in a variety of ways. Often the stress formation will result in a deflection of the micro-cantilever. In these situations the deflection can be detected by deflection of a laser light beam by a reflecting surface of the micro-cantilever. Change in the resistivity of a piezoresistbr integrated onto the micro-cantilever is another method, which has the advantage that it does not depend on a deflection of the micro-cantilever and it does not require optical access to the micro-cantilever. [0009] Change in resonance frequency is another example of a change in a mechanical property. A change in mass of the micro-cantilever can occur if material binds to the micro-cantilever, and such a change will produce a change in the resonance frequency of the micro-cantilever. Such changes can be monitored by actuating the micro-cantilever at a frequency near its resonance frequency, and monitoring changes in the amplitude of the resulting dynamic bending of the micro-cantilever, using methods similar to those described above for the detection of stress formation. [0010] Using these changes in mechanical properties, micro-cantilevers, have been used to detect chemical reactions occurring on the surface of the micro-cantilever, either in gas phase or in liquid phase. For gas phase experiments the measurements have been performed in a gas chamber utilizing optical detection of a micro-cantilever bending. Micro-cantilevers with integrated piezoresistive read-out have been used for thermogravimetry in air. Under ambient conditions the micro-cantilever-based detection technique has proven very sensitive. It has been demonstrated that mass changes down to 0.5 ng and temperature changes down to approximately 10.sup.-5 C can be resolved. Furthermore, a change of surface stress on the order of 10.sup.-5 N/m has been detected. In liquids, J. Chen [J. Chen, Ph.D thesis Simon Fraiser University (1995)] reports on a piezoresistive micro-cantilever for mass change detection. Detection of polystyrene spheres was performed in a 3 water tank in which the micro-cantilever was placed. By vibrating the micro-cantilever, changes in the resonance frequency and thereby mass changes of the micro-cantilever could be monitored. The micro-cantilever deflection was monitored by integrated piezoresistive read-out. [0011] PCT patent application WO99/38007 published Jul. 29 1999 describes a system for detecting analytes in a fluid using functionalised micro-cantilevers mounted in a tube. A bending of the micro-cantilever is induced by molecular interactions on one side of the micro-cantilever.The bending is monitored optically by the reflection of a laser beam of the end of the micro-cantilever. Examples of application include the formation of self assembled monolayers (SAM's) of alkylthiols on a goldcoated micro-cantilever and the partially reversible adsorption of low density lipoproteins. The possibility of testing multiple analytes against multiple analytes is mentioned. A solution for generating a reference signal is proposed exploiting the twisting movement of the micro-cantilever and the ability to distinguish the twisting from the bending movement. Low flow rates are recommended in order to avoid perturbations of the micro-cantilever. This is a clear indication that the envisioned flow system is of macroscopic dimensions. [0012] A micro-cantilever array placed at the top of an open channel has been realised in polymer [C. P. Lee et al., Prooceeding of the .mu.TAS'98 workshop (1998) 245-252; L. P. Lang et al., Sensors and Actuators A 71 (1998) 144-149]. C. P. Lee et al. suggest that these micro-cantilevers can be modified for the use of biochemically functionalized tips for use in atomic force microscopy (AFM) or in scanning near field microscopy (SNOM). Hence, this proposed application is related to surface imaging. [0013] Commercially available micro-cantilevers have been used as sensors in liquid. D. R. Baselt et al. [D. R. Baselt et al., Proceedings of the IEEE. Vol. 85 4 (1997) 672-679] report on piezoresistive micro-cantilevers applied as biosensors using magnetic particles. The coated micro-cantilevers are placed in a liquid cell in which the detection takes place. The micro-cantilevers measure the interaction between particles immobilised on magnetic beads and the immobilised particles on the micro-cantilever surface. If the magnetic beads bind to the surface, the application of a large magnetic field will cause a bending of the micro-cantilever. [0014] U.S. Pat. No. 5,719,324 describes a micro-cantilever based sensor, where a mass change of the micro-cantilever is detected as a change in the resonance frequency of the micro-cantilever. Furthermore, a stress change of a micro-cantilever material is monitored as a micro-cantilever deflection. For mass detection, a piezoelectric actuator oscillates the micro-cantilever and the micro-cantilever deflection is registered by optical read-out. It is mentioned that the mass detection principle can also be applied in liquid. [0015] It is a disadvantage of the above-mentioned systems that micro-cantilever based experiments are carried out in large liquid containers. Such large liquid container systems are very difficult to stabilise thermally. Furthermore, in such large container systems the required volume of chemicals is unnecessary high. [0016] It is a further disadvantage of most of the above-mentioned systems that the micro-cantilever deflection is detected optically. This disadvantage is due to the fact that it may be difficult to obtain optical access to a specific micro-cantilever--especially in the case where a plurality of micro-cantilevers are closely spaced and in the case where the liquid is not transparent. [0017] It is an object of the present invention to integrate micro-cantilevers, micro-bridges or micro-membranes into closed micro-liquid handling systems, in order to provide novel detection mechanisms for monitoring the physical, chemical and biological properties of fluids in such systems. [0018] It is a still further object of the present invention to provide a micro-cantilever, micro-bridge or micro-membrane type sensor having integrated readout. A closed micro-liquid handling system allows laminated flows of different liquids to flow in the channel without mixing, which opens up for new type of experiments and which reduces noise related to the liquid movement. [0019] It is a still further object of the present invention to provide adjacent or very closely spaced micro-cantilevers, micro-bridges or micro-membranes which can be exposed to different chemical environments at the same time by: [0020] Laminating the fluid flow vertically in the micro-channel into two or more streams, so that micro-cantilevers or micro-membranes on opposing sides of the micro-channel are immersed in different fluids, or so that a micro-cantilever, micro-bridge, or micro-membrane is exposed to two different fluids. [0021] Laminating the fluid flow horizontally in the micro-channel, so that micro-cantilevers or micro-bridges recessed to different levels in the micro-channel or micro-membranes placed at the top and at the bottom of the channel are exposed to different fluids. [0022] In this way, changes in viscous drag, surface stress, temperature, or resonance properties of adjacent or closely spaced micro-cantilevers, micro-bridges or micro-membranes induced by their different fluid environments, can be compared. [0023] Neighbouring or very closely spaced micro-cantilevers, micro-bridges or micro-membranes can be coated with different chemical substances using the method just described for immersing adjacent or neighbouring micro-cantilevers, micro-bridges or micro-membranes in different fluids. After coating, the micro-channels can be flushed with other fluids to remove the coating material, and to compare the reactivity of neighbouring or very closely spaced micro-cantilevers, micro-bridges or micro-membranes with different coatings. [0024] It is a still further object of the present invention to provide a micro-cantilever, micro-bridge or micro-membrane based sensor where the liquid volume is minimised in order to reduce the use of chemicals and in order to obtain a system which is easy to stabilise thermally. SUMMARY OF THE INVENTION [0025] The above-mentioned objects are complied with by providing, in a first aspect, a sensor for detecting the presence of a substance in a fluid, said sensor comprising: [0026] means for handling the fluid, said handling means comprising an interaction chamber of micrometer dimensions, an inlet and an outlet, [0027] a first flexible member having a surface, said surface holding a substance, wherein the surface holding the substance is at least partly positioned inside the interaction chamber so that at least part of the substance is exposed to the fluid, and [0028] means for detecting a mechanical parameter associated with the first flexible member, said mechanical parameter being related to the presence of the substance in the fluid. [0029] By micrometer dimension is meant that the interaction chamber has dimensions in the 50-500 microns range (width and depth). The first flexible member may comprise a micro-cantilever having a first and a second end, the first end being attached to the interaction chamber. The micro-cantilever may have a rectangular form and may be approximately 50 .mu.m wide, 200 .mu.m long and 1 .mu.m thick. Continue reading about Transducer for microfluid handling system... Full patent description for Transducer for microfluid handling system Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Transducer for microfluid handling system patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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