Patent Publication Number: US-6909073-B2

Title: Integrated device based upon semiconductor technology, in particular chemical microreactor

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 10/128,989 filed Apr. 22, 2002 now U.S. Pat. No. 6,727,479, which is a continuation-in-part of U.S. patent application Ser. No. 09/874,382 filed Jun. 4, 2001 now U.S. Pat. No. 6,710,311, which claims priority to Italian Patent Application No. TO2001A 000392, filed Apr. 23, 2001, which applications are incorporated herein by reference in their entirety. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not applicable. 
     REFERENCE TO A COMPACT DISK APPENDIX 
     Not applicable. 
     BACKGROUND OF THE INVENTION 
     As is known, proper operation of numerous devices is dependent upon precise regulation of the operating temperature. This may involve difficulties, especially when the devices, for optimizing performances or simply for reducing the overall dimensions, must be integrated on a single chip of semiconductor material also comprising devices that dissipate high powers. In this case, in fact, the problem arises of thermally insulating the regions in which the power devices are formed, which are at a high temperature, from the regions that must be kept at a controlled temperature. 
     For example, the treatment of some fluids involves an increasingly precise temperature regulation, in particular when chemical or biochemical reactions are involved. In addition, frequently the need is felt to use very small amounts of fluid since the fluid is costly and not always readily available. 
     This is, for example, the case of the process of DNA amplification (polymerase chain reaction process, or PCR process) in which the following are important for obtaining good reaction efficiency or even for obtaining the reaction itself: precise temperature control in the various phases (repeated preset thermal cycles are required); the need to avoid as far as possible thermal gradients where the fluid is made to react (so that in these areas there may be a uniform temperature); and also the quantity of fluid used (which is very costly). 
     Other examples of treatment of fluids having the characteristics indicated above are, for instance, linked to the performance of chemical and/or pharmacological analyses, biological tests, etc. 
     At present, various techniques exist that enable thermal control of chemical or biochemical reagents. A first technique uses a reactor comprising a glass or plastic base on which a biological fluid is deposited by means of a pipette. The base rests on a hot-plate called “thermo-chuck”, which is controlled by external instrumentation. 
     Another known reactor comprises a heater, controlled by appropriate instrumentation and on which a biological fluid to be examined is deposited. The heater is supported by a base which also carries a sensor that is arranged in the immediate vicinity of the heater and is also connected to the instrumentation for temperature regulation, so as to enable precise temperature control. 
     Both types of reactors are often enclosed in a protective casing. 
     A common disadvantage of the known reactors described lies in the large thermal mass of the system; consequently, they are slow and have high power absorption. For example, in the case of the PCR process mentioned above, times of about 6-8 hours are required. 
     Another disadvantage of known solutions is that, given the macroscopic dimensions of the reactors, they are able to treat only relatively high volumes of fluids (i.e., minimum volumes of the order of milliliters). 
     The disadvantages referred to above result in very high treatment costs (in the case of the aforementioned PCR process, the cost can amount to several hundreds of dollars); in addition, they restrict the range of application of known reactors to test laboratories alone. 
     In order to overcome the above-mentioned drawbacks, starting from the late eighties miniaturized devices have been developed, and hence ones of reduced thermal mass, which are able to reduce the times required for completing the DNA-amplification process. 
     The first of these devices is described in the article by M. A. Northrup, M. T. Ching, R. M. White, and R. T. Watson, “DNA amplification with a microfabricated reaction chamber”, Proc. 1993 IEET Int. Conf. Solid-State Sens. Actuators, pp. 924-926, 1993, and comprises a cavity formed in a substrate of monocrystalline silicon by anisotropic etching. The bottom of the cavity comprises a thin silicon-nitride membrane, on the outer edge of which heaters of polycrystalline silicon are present. The top part of the cavity is sealed with a glass layer. Thanks to its small thermal mass, this structure can be heated at a rate of 15° C./sec., with cycle times of 1 minute. With this device it is possible to carry out, for a volume of fluid of 50 μl, twenty amplification cycles in periods approximately four times shorter than those required by conventional thermocyclers and with a considerably lower power consumption. 
     However, the process described (as others currently used based upon bonding two silicon substrates pre-formed by anisotropic etches in KOH, TMAH, or other chemical solutions) is costly, has high critical aspects and low productivity, and is not altogether compatible with the usual steps of fabrication applied in microelectronics. 
     Other more recent solutions envisage forming, inside a first wafer of semiconductor material, buried channels connected to the surface via inlet and outlet trenches, and of reservoirs formed in a second wafer of semiconductor material by anisotropic etching, and bonding together the two wafers. 
     This solution, however, is also disadvantageous in that the process is costly, critical, has low productivity, and requires the use of a glass paste containing lead (so-called “glass frit”) for bonding the two wafers together. The problem of thermal insulation may also regard sensors or actuators comprising micro-electromechanical systems (MEMS), which sometimes must be integrated with power devices. In these cases, insulation is required both in order to prevent subjecting the micro-electromechanical structures to dangerous thermal stresses, and because the efficiency and precision of the devices are linked to the presence of well-determined operating conditions. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention relates to an integrated device based upon semiconductor technology, in particular a chemical microreactor. Aspects further include a semiconductor body having a high-temperature operating portion and a low-temperature operating portion, and thermal-insulation means. The thermal-insulation means comprise dissipator means arranged between said high-temperature operating portion and said low-temperature operating portion. The dissipator means comprise a membrane connecting said high-temperature operating portion and said low-temperature operating portion, and a plurality of diaphragms extending from said membrane. 
     Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In order to better understand the present invention, embodiments thereof will now be described, purely by way of non-limiting example, with reference to the attached drawings, in which: 
         FIG. 1  shows a longitudinal cross-section of an integrated device; 
         FIG. 2  is a top plan view of the device of  FIG. 1 ; 
         FIG. 3  is a top plan view of an integrated device according to a first embodiment of the present invention; 
         FIG. 4  is a side view of the integrated device of  FIG. 3 , according to a cross-sectional plane IV—IV of  FIG. 3 ; 
         FIG. 5  is a simplified circuit diagram of one part of the integrated device of  FIG. 3 ; and 
         FIG. 6  is a cross-sectional view of an integrated device according to a second embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     An example of a chemical microreactor integrated in a single chip of semiconductor material will be briefly described in what follows with reference to  FIGS. 1 and 2 . 
     In detail,  FIG. 1  shows a chemical microreactor comprising a semiconductor body  2 , typically of monocrystalline silicon, in which buried channels  3  are formed that extend parallel to a surface  4  of the semiconductor body  2 . Preferably, as indicated in the top view of  FIG. 2  by dashed lines, a plurality of buried channels  3  extend parallel to one another at short distances apart. In this case, the buried channels  3  may have an approximately circular or rectangular section and are arranged at a distance of 50 μm from one another and at a depth of 20-30 μm from the surface  4 . When the buried channels  3  have a rectangular cross section, the shorter side measures approximately 30 μm, and the longer side approximately 200 μm, while the length of the channels is 10 mm, and the total area occupied is 50 mm 2 . Alternatively, it is possible to have a single channel, approximately 10 mm in length, approximately 5 mm in width, and approximately 20 μm in height. In both cases, a total volume is obtained of approximately 1 mm 3  (1 μl). 
     A first insulating layer  5 , for example of silicon dioxide, extends on the surface  4  of the semiconductor body  2  and a polycrystalline-silicon heating element  10  is formed inside the insulating layer  5 . Preferably, the heating element  10  extends substantially over the area occupied by the buried channels  3 , but not over the longitudinal ends of the buried channels  3 , where an inlet opening  16   a  and an outlet opening  16   b  for the channels  3  are formed. The inlet opening  16   a  and outlet opening  16   b  preferably have a length of approximately 5 mm (in a direction perpendicular to the plane of the drawing) and a width of approximately 60 μm. Access trenches  21   a  and  21   b  extend aligned to the inlet and outlet openings  16   a ,  16   b , from the surface  4  as far as the channels  3 , so as to connect the channels  3  to one another in parallel, as well as to an inlet reservoir  19  and an outlet reservoir  20 , as explained hereinafter. 
     Contact regions  11 , for example of aluminum, extend through openings of the first insulating layer  5  and are in electrical contact with two opposite ends of the heating element  10  to enable passage of electric current through the heating element  10  and heating of the underlying area. 
     A sensing electrode  12  extends over the first insulating layer  5 , laterally staggered with respect to the buried channels  3 , and is made up of a multilayer, for example of aluminum, titanium, nickel and gold, in a per se known manner and hence not described in detail herein. 
     A second insulating layer  13 , for example of TEOS (tetra-ethyl orthosilicate) oxide extends on top of the first insulating layer  5  and has an opening through which the sensing electrode  12  protrudes. 
     The inlet reservoir  19  and the outlet reservoir  20  are formed inside a resist layer  18  that overlies the second insulating layer  13 . In particular, and as is shown in the top view of  FIG. 2 , in which the channels  3  are represented by dashed lines, the outlet reservoir  20  is formed as an extension of the outlet opening  16   b  (and hence is connected to the ends of the channels  3  close to the sensing electrode  12 ) and leaves the sensing electrode  12  uncovered. The inlet reservoir  19  is formed, instead, as an extension of the inlet opening  16   a , and is thus connected to the opposite end of the channels  3 . Preferably, the reservoirs  19 ,  20  have a length (in a direction perpendicular to the plane of  FIG. 1 ) of approximately 6 mm; the inlet reservoir  19  has a width (in a horizontal direction in  FIG. 1 ) of between 300 μm and 1.5 mm, preferably approximately 1 mm, so as to have a volume of at least 1 mm 3 , and the outlet reservoir  20  has a width of between 1 and 4 mm, preferably of approximately 2.5 mm. 
     Preferably, the resist layer  18  is formed by a negative resist having a thermal conductivity of between 0.1 and 1.4 W/m K and a coefficient of thermal expansion CTE ≦50 ppm/° K., such as the material known under the name “SU8” (Shell Upon 8) produced by SOTEC MICROSYSTEMS. For example, the resist layer  18  has a thickness of between 300 μm and 1 mm, preferably 500 μm. 
     The microreactor  1 , however, has limits of use due to the absence of thermal insulation between the heater  10  and the region where the sensing electrode  12  is formed. In many cases, in fact, the fluid contained in the outlet reservoir  20  must be kept at a controlled temperature considerably lower than the temperature of the fluid that is inside the channels  3 . In particular, a considerable difference in temperature, for example of about 40-50° C., must be kept between the heater  10  and the region in which the sensing electrode  12  is made. However, the high thermal conductivity of silicon enables the heat generated by the heater  10  to propagate practically throughout the chip in which the microreactor  1  is formed, and consequently it is not possible to obtain the required temperature difference. 
     With reference to  FIGS. 3 and 4 , number  30  designates, as a whole, a chemical microreactor for molecular diagnostics integrated in a die. For simplicity, hereinafter reference will be made to a device of this type; this must not, however, be considered in any way limiting, insofar as the invention may also be applied to different devices. 
     The microreactor  30  comprises a hydraulic circuit  31 , which is partially formed inside a semiconductor body  32 , typically of monocrystalline silicon and having a thickness of approximately 600-700 μm (for example, 670 μm), a plurality of heating elements  33 , a sensing device  34 , and a dissipator element  35 . 
     The hydraulic circuit  31  comprises a plurality of inlet openings  37  for receiving capillaries (not illustrated) through which a fluid containing chemical reagents is introduced, buried channels  38 , and outlet ducts  39  ending in an outlet reservoir  40 . In greater detail, the buried channels  38  are formed inside the semiconductor body  32  and extend parallel to and at a distance from a surface  42  of the semiconductor body  32 . In addition, each of the buried channels  38  is connected to a respective inlet opening  37  and to a respective outlet duct  39  through access trenches  43 , so as to form a duct that extends longitudinally with respect to the semiconductor body  32 . The inlet openings  37  on one side and the outlet ducts  39  and the outlet reservoir  40  on the other are defined in a first resist structure  45  and, respectively, in a second resist structure  46 , which are both formed on top of the surface  42  of the semiconductor body  32 . Preferably, the resist is SU8 and has a thickness of between 300 μm and 500 μm, for example 400 μm. 
     The heating elements  33 , of polycrystalline silicon, are embedded inside the semiconductor body  32 , in the proximity of the surface  42 , and are electrically insulated from the semiconductor body  32  in a per se known manner and not illustrated in detail. In a preferred embodiment of the invention, there are three heating elements  33 , which are arranged transversely above the buried channels  38  and are spaced at equal distances. A first portion  32   a  of the semiconductor body  32 , which is a high-temperature operating portion, and which houses the heating elements  33  and the buried channels  38 . 
     The sensing device  34  comprises a plurality of sensing electrodes  49 , which are arranged on the bottom of the outlet reservoir  40 , and an outlet heating element  50 , which is also embedded in the semiconductor body  32 , in the proximity of the surface  42 . A second portion  32   b  of the semiconductor body  32 , which is a high-temperature operating portion, and which carries the sensing device  34 . 
     A plurality of temperature sensors  53  (for example, five), of a known type, are arranged in proximity of the heating elements  33  and, preferably, in proximity of opposite ends of the outlet heating element  50 . 
     According to the invention, the dissipator element  35  is made in the semiconductor body  32 , between the first high-temperature operating portion  32   a  and the second low-temperature operating portion  32   b . In particular, the dissipator element  35  comprises a membrane  51 , having a thickness of approximately 10-15 μm, arranged underneath the outlet ducts  39 , so as to connect the first portion  32   a  and the second portion  32   b , and extends transversely practically throughout the length of the semiconductor body  32 ; and a plurality of diaphragms  52 , extending orthogonally to the membrane  51  and parallel to one another. The diaphragms  52 , which have a rectangular or trapezoidal cross-section, are separated from one another and from the portions  32   a ,  32   b  of the semiconductor body  32  by thermal-insulation trenches  54 , and are joined laterally by two opposite walls  55 . The thermal-insulation trenches  54  have, in plan view, a substantially rectangular shape and have a length of approximately 400 μm and a width of approximately 10-12 mm. 
     Preferably, the microreactor  1  also comprises a first metal dissipator  57  and a second metal dissipator  58  of known type. In particular, the first metal dissipator  57  is connected, through a first interface layer  59 , to the first portion  32   a  of the semiconductor body  32 , on a surface not facing the surface  42 ; and the second metal dissipator  58  is connected to the second portion  32   b  of the semiconductor body  32  through a second interface layer  60 . The interface layers  59 ,  60  may be of the same material or of different materials; for example, the first interface layer  59  may be of Kapton and the second interface layer  60  may be of a material known as “FR 5 ”. 
     A protective layer  61 , for example of polycarbonate, is bonded on top of the first structure  45  and second structure  46 , and practically overlays the entire surface  42  of the semiconductor body  32 , except for an opening  62  above the outlet reservoir  40 . In this way, the protective layer  61  covers and closes at the top the inlet openings  37  and the outlet ducts  39  of the hydraulic circuit  31 , while the outlet reservoir  40  is uncovered to enable extraction of the fluid at the end of the chemical process. 
     The microreactor  1  is housed in and bonded to a through seat  64  of a supporting plate  65 , of plastic material (for example, FR 5 ). In particular, the semiconductor body  31 , the structures  45 ,  46 , and the protective layer  61  protrude from a first face of the supporting plate  65 , while the metal dissipators  57 ,  58  protrude from a second face, not facing the first face. 
     During use, the heating elements  33  bring the first portion  32   a  of the semiconductor body  32  up to a first operating temperature, for example approximately 90° C., and keep it at this temperature, so as to heat the fluid present in the buried channels  38  and to activate the chemical process. The outlet heating element  50  keeps the sensing device  34  and the second portion  32   b  of the semiconductor body  32  at a second operating temperature, for example approximately 50° C. 
     The dissipator element  35  thermally decouples the first portion  32   a  and the second portion  32   b  from each other, preventing the heat generated by the heating elements  33  from propagating as far as the sensing device  34 . In fact the membrane  51 , of silicon, has high thermal conductivity but a small thickness (10-15 μm), and consequently, as a whole, high thermal resistance. In addition, the diaphragms  52  have the function of cooling fans, increasing the heat-exchange surface and favoring heat dissipation into the environment. The metal dissipators  57 ,  58  contribute to further improving heat dissipation, thus enabling optimal operating conditions to be achieved. 
     The diaphragms  52  also have an important mechanical function of supporting the membrane  51 , which otherwise would be too brittle and easily subject to failure. The diaphragms  52 , which are connected between the side walls  55 , prevent bending of the membrane  51  both in the longitudinal direction and in the transverse direction. 
     According to a further aspect of the invention, the heating elements  33  are activated separately, as shown in FIG.  5 . In particular, the heating elements  33  are here schematically represented by resistors, each of which is connected between ground and a respective controlled current source  71 . The controlled current sources  71  supply the heating elements  33  with respective currents I 1 , I 2 , I 3 .  FIG. 5  also illustrates the outlet heating element  50 , which is also schematically represented as a resistor connected to a constant current source  72 . 
     A control circuit  73 , of known type, has a plurality of inputs  73   a , each of which is connected to the output of a respective temperature sensor  53 , and at least three outputs, each of which is connected to a control terminal  71   a  of a respective controlled current source  71 . The temperature sensors  53  supply the control circuit  73  with respective electrical temperature signals T 1 -T 5 . According to the temperature electrical signals T 1 -T 5 , the control circuit  73  generates and supplies the control terminals  71   a  of the controlled current sources  71  with respective control signals S 1 , S 2 , S 3  for separately and independently controlling the values of the currents I 1 , I 2 , I 3  supplied to the heating elements  33 . In this way it is possible to heat in a uniform way the first portion  32   a  of the semiconductor body  32  and, in particular, the area of the buried channels  38 . 
     The described integrated device has the following advantages. First, the integrated dissipator element provides good thermal insulation between areas to be kept at considerably different operating temperatures. This is particularly important in case of continuous operation of the device. 
     The use of the diaphragms  52  is particularly advantageous. In fact, in addition to increasing the heat-exchange surface, and thus the ability of dispersing heat, the diaphragms  52  have the function of mechanically supporting the membrane  51 , which consequently is unlikely to fail, as discussed previously. It is therefore possible to make membranes with a thickness of a few microns, and with a somewhat high thermal resistance. 
     A further advantage lies in the fact that the entire integrated device may be made employing the usual process steps that are used in microelectronics, and is therefore simple and economical to build. 
     A second embodiment of the invention will be described hereinafter with reference to  FIG. 6 , in which parts that are the same as the ones already shown are designated by the same reference numbers. 
     According to said embodiment, a chemical microreactor  80  comprises the hydraulic circuit  31 , the heating elements  33 , the sensing device  34 , the polycarbonate protective layer  61 , and a dissipator element  81 . 
     In this case, the dissipator element  81  comprises, in addition to the membrane  51 , the diaphragms  52 , and the thermal-insulation trenches  54 , also a cooling chamber  82 , defined between two adjacent diaphragms  52  that are arranged at a distance of, for example, 700 μm. The cooling chamber  82 , which is filled with a coolant (typically water), and at least one of the thermal insulation trenches  54  are made underneath the outlet reservoir  40 . Furthermore, the sensing electrodes  49  and the outlet heating element  50  of the sensing device  34  are made above the membrane  51 . 
     The microreactor  80  is bonded on a supporting plate  83 , for instance of FR 5 , which delimits at the bottom the cooling chamber  82 . The supporting plate  83  is provided with first through openings  84 , which enable circulation of air in the thermal-insulation trenches  54 , and second through openings  85  for connecting the cooling chamber  82  to a delivery capillary  86  and a return capillary  87 , which are in turn connected to a thermostatted reservoir  89 , in which the coolant is basically kept at a constant temperature. A pump  90  takes the coolant from the thermostatted reservoir  89  and sends it to the cooling chamber  82  through the delivery capillary  86 . In this way, the coolant is continuously circulated between the cooling chamber  82 , where it absorbs the heat that is propagated by the heating elements  33  through the membrane  51 , and the thermostatted reservoir  89 , where the heat absorbed is dissipated. 
     In addition to the advantages already described in connection with the microreactor  30  of  FIGS. 3 and 4 , the chemical microreactor  80  of  FIG. 6  has reduced overall dimensions and weight, insofar as the dissipator device  81 , which is more efficient, is formed in part beneath the outlet reservoir  40 . In addition, again on account of the greater efficiency of the dissipator device  81 , it is not necessary to use auxiliary metal dissipators. 
     Finally, it is clear that numerous modifications and variations may be made to the integrated devices described herein, without thereby departing from the scope of the present invention. 
     First of all, the invention can be applied to devices other than chemical microreactors. In particular, it is possible to build, using MEMS technology, various types of micromotors, micro-actuators and sensors (for example, accelerometers or pressure sensors) in which a microstructure and devices with high power dissipation are fabricated inside a single semiconductor wafer. 
     In addition, modifications may also be made to the described chemical microreactor. For example, the number and shape of the diaphragms  52  and of the thermal-insulation trenches  54  may be different from what is illustrated. The circuit for control of the currents supplied to the heating elements  33  may be built in a different way. In particular, the outputs of the temperature sensors  53  can be connected directly to the control terminals  71   a  of the respective controlled current sources  71 . 
     The hydraulic circuit  31  may be modified in order to enable manual introduction, by means of pipettes, of the fluid containing the reagents. In this case, instead of the inlet openings  37  it is possible to provide inlet reservoirs which have a substantially cylindrical shape, are open at the top, and are each connected to a respective buried channel  38 . 
     All references cited, including the above identified journal article and patent application, to which reference has been made above is incorporated by reference herein in its entirety. From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.