Measuring and testing – Liquid analysis or analysis of the suspension of solids in a... – Viscosity
Reexamination Certificate
2000-05-03
2003-06-10
Larkin, Daniel S. (Department: 2856)
Measuring and testing
Liquid analysis or analysis of the suspension of solids in a...
Viscosity
C073S053010, C073S054240, C073S054250, C073S061450
Reexamination Certificate
active
06575020
ABSTRACT:
FIELD OF THE INVENTION
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
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:
1) physical properties such as flow rates viscosity and local temperature
2) chemical properties such as pH and chemical composition
3) biological properties such as identification of organic constituents in fluids, including DNA fragments, proteins, and complete biological cells
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.
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.
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 piezoresistor 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-antilever.
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.
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
−5
C can be resolved. Furthermore, a change of surface stress on the order of 10
−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.
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.
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 &mgr;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.
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.
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.
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.
It is a furt
Boisen Anja
de Charmoy Grey Hasin Francois
Jensenius Tove Maria Henriette
Thaysen Jacob
Cantion A/S
Cygan Michael
Larkin Daniel S.
LandOfFree
Transducer for microfluid handling system does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Transducer for microfluid handling system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transducer for microfluid handling system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3163688