WO2005100235A1

WO2005100235A1 - Piezoresistive microcantilever sensor

Info

Publication number: WO2005100235A1
Application number: PCT/EP2005/051627
Authority: WO
Inventors: Jacob Thaysen
Original assignee: Nanonord A/S
Priority date: 2004-04-15
Filing date: 2005-04-13
Publication date: 2005-10-27

Abstract

The present invention relates to a sensor comprising one or more cantilevers for use in the detection of the presence of a target molecule in a fluid sample, change of temperature or other things that cause a change of stress in the surface of the cantilever. The sensor comprises a cantilever with an integrated piezoresistive element having a pair of wires for applying an electrical field. The piezoresistive element is of p-type silicon and is arranged to have a protruding direction which is orientated along the <110> direction of the silicon. The cantilever is clamped along a clamping line L to the wall of the sensor, so that one or more piezoresistive element clamping line line sections are formed, with a piezoresistive element claming line (L) between the two outermost points including clamping of the piezoresistive element, which piezoresistive element clamping line is at least as long as the shortest distance (H) between the point of the piezoresistive element protruding furthest from the wall. The sensor comprising one or more cantilevers can be produced from standard silicon wafers by etching .

Description

PIEZORESISTIVE MICROCANTILEVER SENSOR

TECHNICAL FIELD

The present invention relates to a sensor comprising one or more cantilevers. The sensor can be used use in the detection of the presence of a target molecule in a fluid sample, change of temperature or other things that causes a change of stress in the surface of the cantilever. In particular the invention relates to a sensor capable of bonding a target molecule to its cantilever surface for thereby resulting in a change of surface stress.

BACKGROUND ART

Sensors comprising a sensor unit in the form of a cantilever and with means for detecting a change of stress in the surface of the cantilever are well known in the art.

In the art of detecting components in fluids, cantilever based sensors with integrated piezoresistors are used as very sensitive mechanical stress sensors. As described in e.g. WO 0066266 and WO 9938007, micro cantilevers can be used for detection of molecular interaction. At least one surface of the cantilever is coated with a capture layer, which capture layer reacts with a target molecule of interest. If the cantilever is exposed to a sample in which the target molecule is present, the target molecule will react with the capture molecule on the cantilever surface and a surface stress change will be generated.

Due to the surface stress change of the cantilever, a mechanical compression, stretch or decompression is applied to the cantilever and thereby also to the piezoresistor, and thereby the resistivity of the piezoresistor changes its value. The mechanical compression or decompression may result in a deflection and/or a stretch and/or a contraction. By measuring the change in resistance, it can be determined whether the target molecule is present in the sample o r not, and if so it may also be possibly to detect the concentration of the target molecule.

Cantilever-based sensors with integrated piezoresistive read-out are described by Thaysen, Ph.D. Thesis, "Cantilever for Bio-Chemical Sensing Integrated in a Microliquid Handling System", September 2001 , Microelektronik Centeret, Technical University of Denmark. Hereby the stress changes on the cantilever sensors can be measured directly by the piezoresistor. Moreover, integrated read-out greatly facilitates operation in solutions since the refractive indices of the fluids do not influence the detection as it will using optical read-out. Each sensor may have a built-in reference cantilever, which makes it possible to subtract background drift directly in the measurement. Furthermore, by functionalizing the reference cantilever with a "dummy" molecule, non-specific binding events occurring on both the measurement and reference cantilever will be cancelled out in the differential measurement.

The two cantilevers may be connected in a Whetstone bridge, and the stress change on the measurement cantilever is detected as tine output voltage from the Whetstone Reference is also made to "Design issues in SOI-based high- sensitivity piezoresistive cantilever devices" by Kassegne et al. Proceedings of the SPIE Conference on Smart Structures and Materials, San Diego, CA, March 17-21 2002.

Today the most well functioning sensors of the present art are sensors made from a silicon substrate where the piezoresistive element is in the form of n- doped (n-type) or p-doped (p-type) silicon. The silicon material is an anisotropic material and has different etch characteristic along different crystal axes.

Since the cantilevers are usually released by a wet etch, such as KOH, the cantilever may e.g. be aligned to the substrate such that a good clamping is obtained. Usually, the wet etch is anisotropically and etches the <111> direction much slower than the other directions. Since the intersection of the {111} plane and the {100} plane are lying along the <110> orientations, it has been found desired to align the cantilever in the <110> direction in order to release it with a good clamping.

SUMMARY OF INVENTION

The objective of the present invention is to provide a sensor comprising one or more cantilevers which can be produced from standard silicon wafers by etching and which has an improved signal or signal/noise ratio tKian according to the prior art cantilever sensors.

This and other objectives as it will be clear from the following description, frias been solved by the invention as it is defined in the claims.

The invention thus provides a sensor with at least one cantilever in the form of a flexible sheet formed unit protruding from a wall of the sensor and comprising a piezoresistive element at least partly integrated with the cantilever and with a pair of wires for applying an electrical field over the piezoresistive element. The sensor is made from standard silicone material, and the piezoresistive element being of p-type silicon, and be arrangecd to have a protruding direction which is orientated along the <110> direction of the silicon, where the protruding direction of the piezoresistive element being the direction of the shortest line between the point of the piezoresistive element protruding longest from the wall and the wall. The cantilever is clamped along a clamping line L to the wall of the sensor, so that one or more piezoresistive element clamping line sections is formed, where the piezoresistive element clamping line L has a length defined as the length of the cantilever clamping line between the two outermost points including clamping of the piezoresistive element. The piezoresistive element clamping line being at least as long as the shortest distance between the point of the piezoresistive element protruding longest from the wall and the wall.

By the sensor according to the invention it has surprisingly been found that an increased signal can be obtained when the surface of the cantilever is subjected to a surface stress. DISCLOSURE OF INVENTION

According to the invention the sensor comprises one or more cantilevers. The shape and size of the sensor and the size, shape and the number of cantilevers as well as its wiring, may e.g. be as disclosed in any one of the patent applications WO 0066266, WO 03071258, WO 03067248, WO 03062135, DK PA 2001 01724, DK PA 2002 00283, DK PA 2002 00125 and DK PA 2002 00195, which with respect to the disclosure concerning structure (shape and size of the sensor and the size, shape and the number of cantilevers as well as its wiring) are hereby incorporated by reference.

In the following the sensor is described with one cantilever, only, but it should be understood that the sensor may have several cantilevers, such as up to 300, e.g. up to 100.

The cantilever may in principle have any cantilever like shape e.g. as the cantilevers described in WO 03062135. The term 'cantilever' is defined as a sheet formed unit linked to a substrate along one or two opposite edge lines. The term 'cantilever shape' thus also includes a bridge, as well as a traditional rectangular, triangular or leaf shaped cantilever.

In one embodiment, the cantilever extends in a length between two endi ngs and are linked in both of its endings to form a cantilevered bridge.

In another and preferred embodiment, the cantilever is a traditional rectangular or leaf shaped cantilever linked to one substrate only. In the following this type of cantilevers are referred to as cantilevers with a free end.

In one embodiment the cantilever is a flexible sheet-formed unit having an average thickness which is thinner than both its average length and its average width, said cantilever preferably have a thickness of between O.05 and 5 μm, such as in the interval of 0.1 μm to 4 μm, such as in the interval of 0.2 μm to 1 μm. In one embodiment the cantilever is a flexible sheet-formed unit having an average thickness which is at least 5 times, preferably at least 50 times less than its average width and average length.

The cantilever have a uniform thickness or the thickness may vary. For simple manufacturing the thickness is essentially uniform.

In one embodiment the cantilever being essentially plane in non stressed state, and having a first and a second opposed sides, the periphery of the cantilever, preferably being essentially rectangular or square formed.

In one embodiment the cantilever has a thickness closer to the piezoresistive element clamping line which is smaller than a thickness of the cantilever longer from the piezoresistive element clamping line. Thereby the stress effect may be transformed to the area closer to the piezoresistive element clamping line, which has been found to increase the signal.

The cantilever comprises a piezoresistive element with a pair of wires for applying an electrical field over the piezoresistive element. In the following, the distance between the wires along the piezoresistive element is defined as the length of the piezoresistive element. This means in practice that the length of the piezoresistive element is the length that the current has to travel through the piezoresistive element. In one embodiment the length of the piezoresistive element is thus defined as the length the current has to travel.

A piezoresistive effect in a material indicates the fractional change in bulk resistivity induced by a small mechanical stress applied to the material.

Single crystalline silicon has a high piezoresistivity, and combined with its excellent mechanical and electronic properties, it makes it a useful material for the conversion of a mechanical signal into an electrical signal.

The piezoresistive element of the present invention is of a p-type silicon (P- doped single crystalline silicon), and are arranged to have a protruding direction which is orientated along the <110> direction of the silicon. Using this material for the piezoresistive element has the large advantages that the sensor can be produced from standard silicon using standard etching methods e.g. as disclosed in WO 0066266, and in "Atomic force microscopy probe with piezoresistive read-out and highly symmetrical wheatstone bridge arrangement" by J. Thaysen et al. Sensors and Actuators 83 (2000) 47-53.

The piezoresistance factor P is depending on the doping level. P is between 0 and 1. For single crystalline silicon P is about 1 at a doping level around 10¹⁸. Further information concerning the P factor and the determination thereof can be found in "1/F Noise Considerations for the Design and Process Optimization of Piezoresistive Cantilevers" by Jonah A. Harley and Thomas W. Kenny. Journal of microelectro mechanical systems. Vol. 9, No. 2, pp 226-235. June 2000. Reference is in particular made to figure 7. Reference is also made to Y. Kanda. "A graphical representation of the piezoresistance coefficients in silicon" IEEE Trans. Electron Devices, Vol. ED-29, pp 64-70, Jan. 1982.

In one embodiment the piezoresistive element is of single crystalline silicon p-doped with 10¹⁶ ions/cm³ or more, such as 10¹⁷ ions/cm³ or more, such as 10¹⁸ ions/cm³ or more, such as 10¹⁹ ions/cm³ or more, such as 10²⁰ ions/cm³ or more.

In one embodiment the piezoresistive element is of single crystalline silicon p-doped with 10²⁰ ions/cm³ or less, such as 10¹⁹ ions/cm³ or less, such as 10¹⁸ ions/cm³ or less, such as 10¹⁷ ions/cm³ or less.

The higher level of doping ions, the lower is the amount of noise, however simultaneously the signal will also be reduced accordingly. The temperature may also influence the noise as well as the signal, and accordingly the effect of temperature should also be considered. The optimal doping level can easily be found by the skilled person based on the present teaching. Optimal doping level will be in the interval 10¹⁶ ions/cm³ - 10²¹ ions/cm³.

In one embodiment the surplus or shortage of electrons due to the doping is within the interval 10¹⁶ ions/cm³ - 10²¹ ions/cm³.

The doping ions may in principle be any type of ions usable for p-doping silicon or mixtures of ions. In one embodiment, when n-type and p-type ions are mixed, it is desired that the piezoresistive element comprise at least 1016 ions/cm3, such as 1017 ions/cm3 or more, such as 1018 ions/cm3 or more, such as 1019 ions/cm3 or more, such as 1020 ions/cm3 or more, more of one of the types than of the other one of the types.

In one embodiment, the piezoresistive element being of single crystalline silicon doped with one or more of the ions boron ion, phosphorous ion, arsenic ion.

Thanks to the invention a highly improved sensor has been provided simply by selecting a shape of the piezoresistive element where the cantilever being clamped along a clamping line L to the wall of the sensor, so that one or more piezoresistive element clamping line sections is formed, and where the piezoresistive element clamping line L has a length defined as the length of the cantilever clamping line between the two outermost points including clamping of the piezoresistive element, the piezoresistive element clamping line being at least as long as the shortest distance between the point of the piezoresistive element protruding longest from the wall and the wall.

It is at present believed that the reason for the obtained improvement is based on the anisotropic character of the silicon material.

The piezoresistivity in single crystalline silicon is anisotropic and therefore the sensitivity is also dependent on the piezoresistor orientation with respect to the silicon crystalline. The contribution to the relative resistance changes from stress generated on a cantilever surface is given by:

ΔR

— = σ,π, + σ_tπ_t (1)

where σι and σ_t is the longitudinal and transverse stress respectively, while πι and π_t indicates the piezoresistive coefficients. For p-type silicon wafer with (100) plane at the surface of the wafer the piezoresistive coefficients at room temperature (in 10^"11 Pa^"1) and doping level about 10¹⁸ cm^"3 (p is approximately 1) is given in table 1.

Table 1 The longitudinal piezoresistive coefficient in the <110> direction is determined as πι=1 /2(π-|-ι+π-.2+7-44). and the corresponding transverse coefficient is πι=1 /2(π-|-ι+π-i2"-T-₄₄)-

Traditional cantilevers used as amplifying cantilevers for topographic measurements was only subjected to longitudinal deflections, and it has for long time been believed that a cantilever with integrated piezoresistor for measuring surface stress was used as used as a longitudinally deflection sensors only, and that the piezoresistor only picked up the longitudinal stress.

However, if we consider the surface stress of a local point of the sensor piezoresistive element, the sensor will in principle bend a cup in all directions if no other forces are involved. The piezoresistive element is thus stressed in all directions in this point, and this stress is divided into two stress composant a longitudinal and a transversal.

The if the stress is equal in transverse and in longitudinal direction the resulting change of signal will thus be ( π_t+ πι ) ^* σ = (-66 + 72) ^* σ = 6^* σ . According to the invention it is believed that the surface stress generated on a cantilever comprising a capture surface, introduces a constant curvature or stretch or contraction at the areas where the surface stress is applied and no bending at places the surface stress is not applied. In areas adjacent a clamping line the bending in the clamping line direction (often also the transversal direction) direction may be limited.

The constant curvature has shown to be obtained for both the transversal and the longitudinal direction. The situation can be visualised by placing the cantilever on a sphere. Since the surface stress changed is observed as a relative change in the resistance it has been found that both the transverse and longitudinal stress has to be considered, and furthermore, it has been found that they can be considered equally, irrespectively of the width and length of the piezoresistive material, when the cantilever is not subjected to other forces, such as a resistive force generated due to clamping. Thus by increasing the clamping effect the contribution by the transverse stress is su press and the effect from the longitudinal stress is thereby increased.

The improved signal obtained by the sensor of the present invention is thus likely due to the suppression of the longitudinal stress.

In the light of this theory it is thus believed that improved results will be obtained by any sensor with a piezoresistive element clamping line which is at least as long as the shortest distance between the point of the piezoresistive element protruding longest from the wall and the wall. In the following the piezoresistive element clamping line is also called the absolute width of the piezoresistive element.

In one embodiment the piezoresistive element clamping line is at least 0.5 times, such as least 2 times, such as at least 3 times as long as the shortest distance between the point of the piezoresistive element protruding longest from the wall and the wall.

In the following the shortest distance between the point of the piezoresistive element protruding longest from the wall and the wall is called the length of the piezoresistive element.

In most situations the cantilever will comprise two or more piezoresistive element clamping line sections, e.g. one in each end of the piezoresistive element, where the piezoresistive element passes from the substrate constituting the wall and into the cantilever and one where the piezoresistive element passes from the cantilever and into the substrate constituting the wall. Each of the piezoresistive element clamping line sections has a length defined as the width of the piezoresistive element at the clamping line.

In one embodiment where the cantilever comprises two or more piezoresistive element clamping line sections, the total length of the two or more piezoresistive element clamping line sections is at least as long as 0.25 times, such as at least as long as 0.5 times, such as at least as long as 1 times, such as at least as long as 1 ,5 times, such as at least as long as 2 times the length of the piezoresistive element.

In a preferred embodiment the absolute width of the piezoresistive element is at least the length of the piezoresistive element, such as at least 1.2 times or more, such as 1.4 times or more, such as 2 times or more, such as 3 or more the length of the piezoresistive element.

In one embodiment the cantilever clamping line being essentially straight, with a transversal direction parallel to the cantilever clamping line, and a longitudinal direction perpendicular thereto.

In one embodiment the amount of piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 50 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the amount of piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 50 μm.

In one embodiment the amount of piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 25 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the amount of piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 25 μm.

In one embodiment amount of piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 0.5 * L is higher, such as at least 1.5 as high, such as at least 2 times higher than the amount of piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 0.5 ^* L.

The piezoresistive element may thus have an equal thickness and/or width along its length or it may have a varying width and/or thickness.

In one embodiment the piezoresistive element is shaped with two or more length sections along its length which is essentially parallel to the length of the piezoresistive element and one or more transversal sections essentially parallel to the cantilever clamping line, at least one transversal section being thinner or narrower than at least one of its length sections.

In one embodiment the piezoresistive element is shaped with two or more length sections along its length which is essentially parallel to the length of the piezoresistive element linked to each other by a conductive not anisotropic material at a distance from the cantilever clamping line preferably from between 0.5 and 1 times the length of the length sections. In this embodiment the contribution to the signal is coming only from the current through the length sections i.e. •R/R=π_t ^* σ_t + π. ^* σι in the length sections of the piezoresistive element wherein σ_t is less than σι due to the clamping effect.

In one embodiment the power dissipation in the piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 50 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the power dissipation in the piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 50 μm.

In one embodiment the power dissipation in the piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 25 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the power dissipation in the piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 25 μm. The piezoresistive element may in principle have any shape e.g. be, latter shaped, meander shaped, U shaped or V shaped. For simple manufacturing U shape will often be preferred. In one embodiment the following shape is used:

PI In practice it is most simple to either provide the piezoresistive element as a straight element when the cantilever is linked to be a bridge or provide the piezoresistive element as a horse shoe shape when the cantilever has a free end.

In one embodiment the piezoresistive element being shaped as a U with two essentially plane opposed sides in non-stressed state, The U shaped piezoresistive element having two legs and a crossbeam, the length of the legs preferably being shorter than the length of the crossbeam.

The piezoresistive element has a longitudinal direction and a transverse direction along the length of the piezoresistive element when an electrical field is applied over the piezoresistive element and the piezoresistive element is subjected to a stress. The longitudinal direction and the transverse direction is aligned to the crystal axis.

The thickness of the piezoresistive element may suitably be at least 10 nm, such as in the interval of 10 nm to 500 nm, such as in the interval of 50 nm to 300 nm, such as in the interval of 100 nm to 200 nm.

As mentioned, the cantilever also comprise a pair of wires for applying an electrical field over the piezoresistor, e.g. as described in any one of the patent applications WO 0066266, DK PA 01724 DK PA 2002 00283, DK PA 200200125 and DK PA 2002 00195.

The cantilever may preferably comprise a single crystalline silicon piezoresistive element encapsulated in a single crystalline silicon electrically shield. As mentioned a such cantilever may be produced from a bulk silicon material which is etched to form the cantilever and the wall clamping the cantilever. The piezoresistive element may e.g. be provided by doping preferably using ion-implanting as it is generally known in the art and as disclosed in "properties of Nitrogen- Implanted SOI Substrates", by Stanley W. Polchlopek et al, IEEE Transaction on electron devices. Vol. 40.No. 2, February 1993; "Basic mechanism involved in the Smart-Cut® process" by B. Aspar et al. Microelectronic engineering, 36 (1997) 223-240;"Application of hydrogen ion beams to silicon on insulator material technology" by Michel Bruel. Nuclear Instruments and Methods in Physics Research B 108 (1996) 313-319; "Ultrashallow junctions or ultrathin SOI?" by M.I. Current et al. Solid state Technology, September 2000; "New technologies for silicon-insulator". European semiconductor, February 2O02; and "Environmental sensors based on micromashined cantilevers with integrated read-out" by Anja Boisen et al. Ultramicroscopy 82 (2000) 11-16.

In one embodiment of the sensor according to the invention, where the cantilever comprises two major surfaces, and at least a part of one or both of the major surfaces constitutes a capture surface, the piezoresistive element has a neutral plan distance of 50 nm or less, such as 100 nm or less, such as 200 nm or less, such as 400 nm or less, such as 1 μm or less, such as 3 μm or less,. The neutral plan distance is measured as the shortest distance between the middle plan of the piezoresistive element and the neutral plan. The middle plan of the piezoresistive element is defined as the middle plan through the piezoresistive element which is parallel to the neutral plan. The neutral plan is defined as the plan along which the sum of the compressive and tensile stress acting on the piezoresistive element is as close to zero as possible.

In one embodiment, the cantilever further comprise a current shield, e.g. as described in DK PA 2002 00884 DK fi led June 7, 2002.

The shield may have a diffusion barrier which is sufficient to prevent the diffusion of an electrolyte to leak current from the piezoresistor when an acidic liquid at a pH of 4 is held in contact with the capture surface for a period of 1 or even 2 minutes or even 10 minutes under standard conditions. In one embodiment the shield is of a non-conducting material selected from the group consisting of nitrides, such as silicon nitride and tantalum nitride, non-conducting polymers, such as octafunctional epoxidized novalac, metal oxides, such as aluminium oxide, ceramics, diamond films, silicon carbide, tantalum oxide, silicon, glass, mixtures and combinations thereof.

In one embodiment the piezoresistive element is of doped p-type single crystalline silicon and the shield is of doped n-type single crystalline silicon, preferably a n-type single crystalline silicon with a doping level which is lower than the doping level of the p-type single crystalline silicon piezoresistive element. The n-type single crystalline silicon shield may e.g. have a doping ion concentration of 10²⁰ cm^"3 or less, such as a doping ion concentration of 10¹⁹ cm^"3 or less, such as a doping ion concentration of 10¹⁸ cm^"3 or less, such as a doping ion concentration of 10¹⁷ cm^"3 or less, such as a doping ion concentration of 10¹⁶ cm^"3 or less, such as a doping ion concentration of 10¹⁵ cm^"3 or less.

In one embodiment the cantilever comprise a bottom shield layer and a top shield layer, and an edge shield layer. The bottom shield layer, top shield layer and edge shield layer constitute the shield.

A sensor wherein the cantilevers comprise a shield may preferably be used for detection of a substance in a liquid, such as an aqueous liquid.

The sensor according to the invention may preferably comprise a cantilever with a capture surface. In one embodiment wherein the cantilever comprises two major surfaces, at least a part of one of the surfaces comprises a capture surface. The capture surface may e.g. be a coating as described in any one of the applications DK PA 2002 00283 and DK PA 2002 00125 or in US 6289717, WO 0133226 or WO 0014539, which with respect to the disclosure concerning the capture surface are hereby incorporated by reference.

The capture surface may e.g. be provided by a capture layer comprising a coating of a material selected from the group consisting of oxides, sulphides and selenides. In one embodiment of the sensor according to the invention, the capture surface is a surface of a capture coating comprising a capture layer, wherein said capture layer is a layer comprising a detection ligand, said detection ligand may be a member of a specific binding pair or it may be adapted for capturing a group of components or even for unspecific binding. The detection ligand is preferably selected from the group consisting of RNA oligos, DNA oligos, PNA oligos, proteins, enzymes, receptors, peptides, hormones, blood components, antigen and antibodies.

In one embodiment of the sensor according to the invention, the capture surface is a surface of a capture coating comprising a capture layer, of polymer, hydrogel or metal/metal containing component e.g. comprising a functional group selected from the group consisting of carboxylic acids, sulfonic acid derivatives, esters, acid halides, acid hydrazides, semicarbazides, thiosemicarbaxides, nitriles, aldehydes, ketones, alcohols, thioles, disulphides, amines, hydrazines, ethers, epoxides, sulphides, halides and derivatives thereof.

The capture coating could in principle have any thickness. If the capture coating is very thick the sensitivity may be reduced due to stiffness of cantilever. A desired thickness could e.g. be from molecular thickness to 2000 nm, such as up to, 2, 5, 10 or 50 molecule layers, or e.g. between 0.5 nm and 1000 nm, such as between 1 and 500 nm, such as between 10 and 200 nm.

In one embodiment both or a part of both of the two major sides of the cantilever comprise a capture surface. The capture surfaces may be identical or they may differ from each other e.g. with respect to size of area covered, type of capture molecules and/or concentrations thereof. In one embodiment the capture surface on one major side of a cantilever is essentially identical, - both with respect to size of area covered, type of capture molecules and concentrations - to the capture surface on the other one of the two opposite major surfaces of the cantilever. In this situation the stress generated on the cantilever when subjected to a fluid containing the target molecules, will be equal on both sides of the cantilever, and consequently, if the cantilever is of the type with a free end, the cantilever will not bend, but only stretch or contract.

In practice it is very cumbersome to produce a cantilever with two opposite major sides with identical capture surfaces. Thus, the cantilever will in most situations, even when carrying capture surfaces on both of each major sides, be subjected to at least a slightly bending due to different stress generated on the opposite major sides of the cantilever.

The cantilever may in preferably have a longer length than the piezoresistive element, such a .5 times, such as 2 times, such as 4 times longer than the piezoresistive element.

To obtain a good signal it is desired that the capture surface includes a surface area of the cantilever relatively close to the piezoresistive element clamping line, preferably the surface area includes at least some of the surface which is not longer from the piezoresistive element clamping line than the length of the piezoresistive element, such as at least some of the surface which is not longer from the piezoresistive element clamping line than half the length of the piezoresistive element, such as at least some of the surface which is not longer from the piezoresistive element clamping line than 25 % of the length of the piezoresistive element.

The sensor may preferably comprise one or more fluid chambers (e.g. liquid chambers). In one embodiment the one or more cantilevers partly or totally protrudes into the fluid chamber(s) so that a fluid applied in the chamber is capable of coming into contact with part of the surface of the cantilever(s).

The fluid chamber or chambers may e.g. be in the form of interaction chamber(s), preferably comprising a channel for feeding a fluid such as a liquid into the interaction chamber(s). In one embodiment at least 50 %, more preferably substantially all of the capture surface of the cantilever(s) is positioned inside the fluid interaction chamber(s).

The sensor may e.g. be prepared as described in DK PA 2002 00884 DK with the difference that the piezoresistive element is shaped as disclosed above.

FIGURES AND EXAMPLES

Embodiments of the invention will be described further with reference to the figures and examples.

Fig. 1 is a schematic illustration of section of a first sensor according to the invention including a cantilever clamped to a wall.

Fig. 2 is a perspective view of the sensor section shown in fig. 1.

Fig. 3 is a schematic illustration of section of a second sensor according to the invention including a cantilever clamped to a wall.

Fig. 4 is a perspective view of the sensor section shown in fig. 3.

Fig. 5 is a schematic illustration of section of a third sensor according to the invention including a cantilever clamped to a wall.

Fig. 6 is a piezoresistance coefficient diagram for p-Si.

Fig. 7 shows the surface of a cantilever clamped to a wall and subjected o stress. The sensor section shown in fig 1 and 2 includes a cantilever 1 clamped to a wall 2, along a clamping line L. The cantilever comprises a piezoresistive element 3 formed as a horse shoe (also referred to as a U shape). The length of the clamping line is the distance between line the two outermost points x, x' including clamping of the piezoresistive element. The length of the piezoresistive element clamping line sections is the sum of the piezoresistive element at the clamping line i.e. y+y'. The absolute width of the piezoresistive element is the length of the clamping line x-x'. The length of the piezoresistive element H is the shortest distance between the point of the piezoresistive element protruding longest from the wall and the wall 2. The sockets 4 are for the connection to wires.

As it can be seen the piezoresistive element of the sensor section shown in figs. 1 and 2 has a piezoresistive element clamping line L, which is longer than the length of the piezoresistive element H.

Fig. 3 and 4 shows a variation of the sensor section shown in Figs. 1 and 2, including a cantilever 11 clamped to a wall 12, along a clamping line L The cantilever 11 comprises a piezoresistive element 13 formed as a horse shoe. The length of the clamping line clamping line L is much longer than the length of the piezoresistive element H. The cantilever 11 is protruding long beyond the piezoresistive element 13.

Fig. 5 shows another variation of the sensor section shown in Figs. 1 and 2, including a cantilever 21 clamped to a wall 22, along a clamping line L The cantilever 21 comprises a piezoresistive element 23 formed as an M. The length of the clamping line clamping line L is longer than the length of the piezoresistive element H. The sockets 24 are for the connection to wires.

Fig. 6 shows the piezoresistive coefficients for πl and πt for p-type (At room temperature, in 10-11 Pa-1) It is seen that the p-type piezoresistive coefficients are very symmetrical and thus will set off each other if the stress ii equally distribution in all directions. Fig. 7 shows the surface of a cantilever clamped to a wall and subjected o stress. The gold was applied in the form of a film. During to the application of the gold film, the gold film was stretched in all directions, so that cantilever surface after the release of the gold layer was subjected to a stress. The stress of the surface was determined by finite element simulation. In the cantilever surface shown in figure 7 the stress is indicated by the white/grey/black colour. The darker the colour the higher is the stress that is measured. In area 32 adjacent the clamping line 31 the bending in the clamping line direction is limited and accordingly the level of stress measured is less than longer away 33 from the clampincj line. The limitation of stress in the area 32 adjacent the clamping line 31 has found to be mainly limitation in the transversal stress. It was found that the stress in the transverse direction can be considered effected (limited) of the clamping when the distance X from the clamping is about X<0.25xH where H is the length of the cantilever.

Example 1 A simulation of the surface stress sensitivity for two cantilevers with the following dimensions, and with the piezoresistor placed in the <110> direction has been performed. The cantilevers have length of about 120 μm and a width of about 50 μm. The width of the cantilever (the piezoresistive element clamping line length L) were for both cantilevers about 40 μm, The length H of the piezoresistive element of cantilever A was about 40 μm and the length of the piezoresistive element of cantilever B was about 100 μm

A stress test is simulated on both cantileve rs and is found that the sensitivity of the cantilever A is significantly higher than the sensitivity of cantilever B.

Example 2

Two almost identical piezoresistive cantilevers, wherein the cantilevers differs in that one of the piezoresistive cantilevers is longer than the other is provided. The cantilevers have the dimensions and materials as disclosed in example 1.

The AU surfaces of cantilevers is subjected to Mercaptohexanol. Immobilization of Mercaptohexanol is performed due to the binding between the -SH group in Mercaptohexanol and the* gold layer. The immobilization of Mercaptohexanol is finalized when a complete monolayer is formed on the gold surface. Since the surface stress of t ie cantilevers are changing during this procedure, this can be monitored a.s a change in signal from the piezoresistive cantilevers. When the mono layer has been formed the signal will become constant. The amplitude of the signal is then defined as difference between the signal before the introduction of Mercaptohexanol and the signal from the piezoresistors after t e Mercapothexanol monolayer is formed on the cantilever gold.

In the experiment, the cantilevers are inserted in a micro liquid handling system as described in WO 0066266. The V=2.5 V is applied to the Wheatstone bridge (input voltage) and the signal from the Wheatstone bridge is monitored by a voltmeter. First, water is pumped through the system in • order to stabilize the system. Hereafter, 1 rπM Mercaptohexanol is introduced in the micro liquid handling system and the signal starts to change. It is observed that the signal from the piezoresistor which is shortest is significantly higher that the signal from the other piezoresistor.

Claims

1. A sensor comprising at least one cantilever in the form of a flexible sheet formed unit protruding from a wall of the sensor said sensor comprises a piezoresistive element at least partly integrated with the cantilever and with a pair of wires for applying an electrical field over the piezoresistive element, the piezoresistive element being of p-type silicon, and be arranged to have a protruding direction which is orientated along the <110> direction of the silicon, where the protruding direction of the piezoresistive element being the direction of the shortest line between the point of the piezoresistive element protruding longest from the wall and the wall, the cantilever being clamped along a clamping line L to the wall of the sensor, so that one or more piezoresistive element clamping line sections is formed, where the piezoresistive element clamping line L has a length defined as the length of the cantilever clamping line between the two outermost points including clamping of the piezoresistive element, the piezoresistive element clamping line being at least as long as the shortest distance between the point of the piezoresistive element protruding longest from the wal 1 and the wall.

2. A sensor according to claim 1 wherein the piezoresistive element clamping line being at least 0.5 times, such as least 2 times, such as at least 3 times as long as the shortest distance between the point of the piezoresistive element protruding longest from the wal I and the wall.

3. A sensor according to any one of the claims 1 and 2 comprising two or more piezoresistive element clamping line sections, wherein each of the piezoresistive element clamping line sections has a length defined as the width of the piezoresistive element at the clamping line, the total length of the two or more piezoresistive element clamping line sections being at least as long as 0.25 times, such as at least as long as 0.5 times, such as at least as long as 1 times, such as at least as long as 1 ,5 times, such as at least as long as 2 times, the shortest distance between the poi nt of the piezoresistive element protruding longest from the wall and the wall.

4. A sensor according to any one of the preceding claims wherein the cantilever clamping line being essentially straight, with a transversal direction parallel to the cantilever clamping line, and a longitudinal direction perpendicular thereto.

5. A sensor according to any one of the preceding claims wherein the amount of piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 50 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the amount of piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 50 μm.

6. A sensor according to claim 5 wherein the amount of piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 25 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the amount of piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 25 μm.

7. A sensor according to any one of the preceding claims wherein the amount of piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 0.5 * L is higher, such as at least 1.5 as high, such as at least 2 times higher than the amount of piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 0.5 ^* L

8. A sensor according to any one of the preceding claims wherein the power dissipation in the piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 50 μrn is higher, such as at least 1.5 as high, such as at least 2 times higher than the power dissipation in the piezoresistive element material of the cantilever which is longer away from the cantilever clamping line less than 50 μrm

9. A sensor according to claim 7 wherein the power dissipation in the piezoresistive element material of the cantilever with a distance from the cantilever clamping line less than 25 μm is higher, such as at least 1.5 as high, such as at least 2 times higher than the power dissipation in the piezoresistive element material of the cantilever which is lo nger away from the cantilever clamping line less than 25 μm

10. A sensor according to any one of the preceding clai ms wherein the cantilever comprises a single crystalline silicon piezoresistive element encapsulated in a single crystalline silicon electrically shield.

11. A sensor according to any one of the preceding clai ms wherein the cantilever being produced from a bulk silicon material which is etched to form the cantilever and the wall clamping the cantilever.

12. A sensor according to claim 10 wherein the piezoresistive element being provided by doping preferably using ion-implanting.

13. A sensor according to any one of the preceding clai ms wherein the piezoresistive element is encapsulated in a shield of a non-conducting material selected from the group consisting of nitrides, such as silicon nitride and tantalum nitride, non-conducting polymers, such as octafunctional epoxidized novalac, metal oxides, such as aluminium oxide, ceramics, diamond films, silicon carbide, tantalum oxide, silicon, silicon oxide, glass, mixtures and combinations thereof.

14. A sensor according to any one of the preceding claims wherein the cantilever has a thickness in the interval of 0.05 μm to 5 μm- such as in the interval of 0.1 μm to 4 μm, such as in the interval of 0.2 μm to 1 μm.

15. A sensor according to any one of the preceding claims wherein the cantilever has a uniform thickness.

16. A sensor according to any one of the preceding claims 1-4 wherein the cantilever has a thickness closer to the piezoresistive element clamping line which is smaller than a thickness of the cantilever longer from the piezoresistive element clamping line.

17. A sensor according to any one of the preceding claims wherein the piezoresistive element has a thickness in the interval of 10 nm to 500 nm, such as in the interval of 50 nm to 300 nm, such as in the interval of 100 nm to 200 nm, the thickness preferably being uniform.

18. A sensor according to any one of the preceding claims wherein the piezoresistive element being U shaped, latter s-haped, meander shaped or V shaped.

19. A sensor according to any one of the preceding claims wherein the piezoresistive element being of single crystalline silicon doped with one or more of the ions: boron, arsenic and phosphor

20. A sensor according to any one of the preceding claims wherein the piezoresistive element being of single crystal line silicon doped with 10¹⁶ ions/cm³ or more, such as 10¹⁷ ions/cm³ or more, such as 10¹⁸ ions/cm³ or more, such as 10¹⁹ ions/cm³ or more, such as 10²⁰ ions/cm³ or more.

21. A sensor according to any one of the preceding claims wherein the piezoresistive element being of single crystal line silicon doped with 10²¹ ions/cm³ or less, 10²⁰ ions/cm³ or less, such as 0¹⁹ ions/cm³ or less, such as 10¹⁸ ions/cm³ or less, such as 10¹⁷ ions/cm³ or less.

22. A sensor according to any one of the receding claims wherein the cantilever being essentially plane in non stressed state, and having a first and a second opposed sides, the periphery of the cantilever, preferably being essentially rectangular or square formed.

23. A sensor according to any one of the preceding claims wherein the piezoresistive element being shaped as a U with two essentially plane opposed sides in non-stressed state, The U shaped piezoresistive element having two legs and a crossbeam, the length of trie legs preferably being shorter than the length of the crossbeam.

24. A sensor according to any one of the preceding claims, wherein the cantilever comprises two major surfaces, at least a part of one of the surfaces comprises a capture surface.

25. A sensor according to claim 24 wherein said capture surface is provided by a capture layer comprising a coating of a material selected from the group consisting of oxides, sulphides and selenides.

26. A sensor according to claim 24 wherein said capture surface is provided by a capture layer comprising one or more of the materials selected from the group consisting of metals, such as Au, Ag and Pt and polymeric materials, such as polymeric materials selected from the group consisting of thermoplastics such as thermoplastic elastomers including block copolymer such as SEBS, SBS, SIS, TPE-polyether-amide, TPE-polyether-ester, TPE- urethanes, TPE PP/NBR, TPE-PP/EPDM, TPE-vulcanisates and TPE- PP/IIR; rubbers such as butadiene rubber, isoprene rubber, silicon rubber, nitrile rubber, styrene-butadiene rubber and urethane rubber; acrylates; polyolefins such as polyethylene, polypropylene and polybutylene including its isomers; polyesters; polystyrene; polyacrylates; polyethers; and polyurethane.

27. A sensor according to claim 24 wherein said capture surface is provided by one or more specific or unspecific binding partners, preferably selected from the group consisting of one or more binding partners in the form of one or more of the binding components selected from the group comprising one or more biomolecules of microbial, viral, fungal, plant, animal or human origin, synthetic molecules resembling them, explosives, alcohols, and drugs, the binding components preferably comprise one or more molecules selected from the group consisting of proteins, glyco proteins, nucleic acids, such as RNA, DNA including cDNA, PNA, LNA, oligonucleotides, peptides, hormones, antigens, antibodies, lipids, sugars, carbohydrates, and complexes including one or more of these molecules, said biomolecule or molecules preferably bei ng selected from the group consisting of nucleic acids, antibodies, proteins, protein complexes, enzymes, drugs and receptors.

28. A sensor according to claim 24 wherein said capture surface is provided by a capture surface comprising one or more binding partners in the form of molecules comprising a functional group selected from the group consisting of -OH, -CHO, -COOH, -SO3H, -CN- -NH2, -SH , -COSH, COOR, halide.

29. A sensor according to any one of the preceding claims wherein said sensor comprises one or more fluid chambers, said one or more cantilevers partly or totally protrudes into said fluid chamber(s) so that a fluid applied in the chamber is capable of coming into contact -with part of the surface of the cantilever(s).

30. A sensor according to any one of the preceding claims wherein said sensor is adapted for use in detection of a target substance in a fluid, such as a gas or a liquid.

31. A sensor according to any one of the preceding claims wherein said sensor is a stress sensor, the resistivity of the piezoresistive element is changing in relation to stress generated on the cantilever capture surface.