Electronic devices and components have found numerous applications in chemistry and biology (more generally, “life sciences”), especially for detection and measurement of various chemical and biological reactions and identification, detection and measurement of various compounds. One such electronic device is referred to as an ion-sensitive field effect transistor, often denoted in the relevant literature as an “ISFET” (or pHFET). ISFETs conventionally have been explored, primarily in the academic and research community, to facilitate measurement of the hydrogen ion concentration of a solution (commonly denoted as “pH”).
More specifically, an ISFET is an impedance transformation device that operates in a manner similar to that of a MOSFET (Metal Oxide Semiconductor Field Effect Transistor), and is particularly configured to selectively measure ion activity in a solution (e.g., hydrogen ions in the solution are the “analytes”). A detailed theory of operation of an ISFET is given in “Thirty years of ISFETOLOGY: what happened in the past 30 years and what may happen in the next 30 years,” P. Bergveld, Sens. Actuators, 88 (2003), pp. 1-20 (“Bergveld”), which publication is hereby incorporated herein by reference in its entirety.
Details of fabricating an ISFET using a conventional CMOS (Complementary Metal Oxide Semiconductor) process may be found in Rothberg, et al., U.S. Patent Publication No. 2010/0301398, Rothberg, et al., U.S. Patent Publication No. 2010/0282617, and Rothberg et al, U.S. Patent Publication 2009/0026082; these patent publications are collectively referred to as “Rothberg”, and are all incorporated herein by reference in their entirety. In addition to CMOS, however, biCMOS (i.e., bipolar and CMOS) processing may also be used, such as a process that would include a PMOS FET array with bipolar structures on the periphery. Alternatively, other technologies may be employed wherein a sensing element can be made with a three-terminal devices in which a sensed ion leads to the development of a signal that controls one of the three terminals; such technologies may also include, for example, GaAs and carbon nanotube technologies.
Taking a CMOS example, a P-type ISFET fabrication is based on a p-type silicon substrate, in which an n-type well forming a transistor “body” is formed. Highly doped p-type (p+) regions S and D, constituting a source and a drain of the ISFET, are formed within the n-type well. A highly doped n-type (n+) region B may also be formed within the n-type well to provide a conductive body (or “bulk”) connection to the n-type well. An oxide layer may be disposed above the source, drain and body connection regions, through which openings are made to provide electrical connections (via electrical conductors) to these regions. A polysilicon gate may be formed above the oxide layer at a location above a region of the n-type well, between the source and the drain. Because it is disposed between the polysilicon gate and the transistor body (i.e., the n-type well), the oxide layer often is referred to as the “gate oxide.”
Like a MOSFET, the operation of an ISFET is based on the modulation of charge concentration (and thus channel conductance) caused by a MOS (Metal-Oxide-Semiconductor) capacitance. This capacitance is constituted by a polysilicon gate, a gate oxide and a region of the well (e.g., n-type well) between the source and the drain. When a negative voltage is applied across the gate and source regions, a channel is created at the interface of the region and the gate oxide by depleting this area of electrons. For an n-well, the channel would be a p-channel (and vice-versa). In the case of an n-well, the p-channel would extend between the source and the drain, and electric current is conducted through the p-channel when the gate-source potential is negative enough to attract holes from the source into the channel. The gate-source potential at which the channel begins to conduct current is referred to as the transistor's threshold voltage VTH (the transistor conducts when VGS has an absolute value greater than the threshold voltage VTH). The source is so named because it is the source of the charge carriers (holes for a p-channel) that flow through the channel; similarly, the drain is where the charge carriers leave the channel.
As described in Rothberg, an ISFET may be fabricated with a floating gate structure, formed by coupling a polysilicon gate to multiple metal layers disposed within one or more additional oxide layers disposed above the gate oxide. The floating gate structure is so named because it is electrically isolated from other conductors associated with the ISFET; namely, it is sandwiched between the gate oxide and a passivation layer that is disposed over a metal layer (e.g., top metal layer) of the floating gate.
As further described in Rothberg, the ISFET passivation layer constitutes an ion-sensitive membrane that gives rise to the ion-sensitivity of the device. The presence of analytes such as ions in an analyte solution (i.e., a solution containing analytes (including ions) of interest or being tested for the presence of analytes of interest), in contact with the passivation layer, particularly in a sensitive area that may lie above the floating gate structure, alters the electrical characteristics of the ISFET so as to modulate a current flowing through the channel between the source and the drain of the ISFET. The passivation layer may comprise any one of a variety of different materials to facilitate sensitivity to particular ions; for example, passivation layers comprising silicon nitride or silicon oxynitride, as well as metal oxides such as silicon, aluminum or tantalum oxides, generally provide sensitivity to hydrogen ion concentration (pH) in an analyte solution, whereas passivation layers comprising polyvinyl chloride containing valinomycin provide sensitivity to potassium ion concentration in an analyte solution. Materials suitable for passivation layers and sensitive to other ions such as sodium, silver, iron, bromine, iodine, calcium, and nitrate, for example, are known, and passivation layers may comprise various materials (e.g., metal oxides, metal nitrides, metal oxynitrides). Regarding the chemical reactions at the analyte solution/passivation layer interface, the surface of a given material employed for the passivation layer of the ISFET may include chemical groups that may donate protons to or accept protons from the analyte solution, leaving at any given time negatively charged, positively charged, and neutral sites on the surface of the passivation layer at the interface with the analyte solution.
With respect to ion sensitivity, an electric potential difference, commonly referred to as a “surface potential,” arises at the solid/liquid interface of the passivation layer and the analyte solution as a function of the ion concentration in the sensitive area due to a chemical reaction (e.g., usually involving the dissociation of oxide surface groups by the ions in the analyte solution in proximity to the sensitive area). This surface potential in turn affects the threshold voltage of the ISFET; thus, it is the threshold voltage of the ISFET that varies with changes in ion concentration in the analyte solution in proximity to the sensitive area. As described in Rothberg, since the threshold voltage VTH of the ISFET is sensitive to ion concentration, the source voltage VS provides a signal that is directly related to the ion concentration in the analyte solution in proximity to the sensitive area of the ISFET.
Arrays of chemically-sensitive FETs (“chemFETs”), or more specifically ISFETs, may be used for monitoring reactions—including, for example, nucleic acid (e.g., DNA) sequencing reactions, based on monitoring analytes present, generated or used during a reaction. More generally, arrays including large arrays of chemFETs may be employed to detect and measure static and/or dynamic amounts or concentrations of a variety of analytes (e.g., hydrogen ions, other ions, non-ionic molecules or compounds, etc.) in a variety of chemical and/or biological processes (e.g., biological or chemical reactions, cell or tissue cultures or monitoring, neural activity, nucleic acid sequencing, etc.) in which valuable information may be obtained based on such analyte measurements. Such chemFET arrays may be employed in methods that detect analytes and/or methods that monitor biological or chemical processes via changes in charge at the chemFET surface. Such use of ChemFET (or ISFET) arrays involves detection of analytes in solution and/or detection of change in charge bound to the chemFET surface (e.g. ISFET passivation layer).
Research concerning ISFET array fabrication is reported in the publications “A large transistor-based sensor array chip for direct extracellular imaging,” M. J. Milgrew, M. O. Riehle, and D. R. S. Cumming, Sensors and Actuators, B: Chemical, 111-112, (2005), pp. 347-353, and “The development of scalable sensor arrays using standard CMOS technology,” M. J. Milgrew, P. A. Hammond, and D. R. S. Cumming, Sensors and Actuators, B: Chemical, 103, (2004), pp. 37-42, which publications are incorporated herein by reference and collectively referred to hereafter as “Milgrew et al.” Descriptions of fabricating and using ChemFET or ISFET arrays for chemical detection, including detection of ions in connection with DNA sequencing, are contained in Rothberg. More specifically, Rothberg describes using a chemFET array (in particular ISFETs) for sequencing a nucleic acid involving incorporating known nucleotides into a plurality of identical nucleic acids in a reaction chamber in contact with or capacitively coupled to chemFET, wherein the nucleic acids are bound to a single bead in the reaction chamber, and detecting a signal at the chemFET, wherein detection of the signal indicates release of one or more hydrogen ions resulting from incorporation of the known nucleotide triphosphate into the synthesized nucleic acid.
Prior techniques for testing a chemically-sensitive transistor based array, such as an ion-sensitive field effect transistor (ISFET) array, included “wet testing.” An ISFET array is sensitive to changes in chemical composition in a fluid. Accordingly, ISFET arrays were commonly tested by flowing one or more liquids over the array (e.g. liquids having different pH values), reading out the response for each ISFET element in the array, and determining whether the element is operating properly. Although wet testing has the benefit of testing an ISFET under intended operational conditions, wet testing is considered impractical in most circumstances.
In particular, wet testing is cumbersome and impractical for high volume manufacturing. Also, wet testing exposes the device to fluids that may cause corrosion and prevent the device from being fully dried before normal operations. Moreover, exposure of the device to liquids may create defects in the device or future contamination. For these reasons, once a device is exposed to fluids, a manufacturer will typically not accept the device.
Accordingly, there is a need in the art for dry testing a chemically-sensitive transistor based device.
Embodiments of the present invention provide a method of testing a chemical a chemical detecting device comprised of an array of pixel elements where each pixel element includes a chemically-sensitive transistor having a source terminal, a drain terminal, and a floating gate terminal. The method may include connecting of a group of the chemically-sensitive transistors' source terminals in common, applying first test voltages at the source terminals of the group, measuring corresponding first currents at the drain terminals produced by the first test voltages, and calculating resistance values based on the first test voltages and currents. The method may also include applying second test voltages at the source terminals of the group to operate the group in a different operational mode, wherein the second test voltages are based at least partially on the resistance values, and measuring a corresponding second set of currents at the drain terminals produced by the second test voltages. Based on the second test voltages and currents and operational properties of the chemically-sensitive transistors, calculating a floating gate voltage of each chemically-sensitive transistor in the group.
Embodiments of the present invention provide a method of dry testing an array of chemically-sensitive transistors having a source, a drain, and a floating gate. The method may include applying first test voltages to a common source connected group of the chemically-sensitive transistors; calculating a resistance based on the first test voltages and currents produced by the first set of test voltages; applying second test voltages, where the second test voltages drive the chemically-sensitive transistors to transition among a plurality of operational modes and where the second test voltages are based partially on the calculated resistance; calculating a floating gate voltage of each driven chemically-sensitive transistor; and determining if each calculated floating gate voltage is within a predetermined threshold.
Embodiments of the present invention provide a device including an array of chemical detection elements and a testing circuit. Each element may include a chemically-sensitive field effect transistor having a semiconductor body terminal, a source terminal, a drain terminal, and a floating gate terminal. The testing circuit may include a plurality of driving voltage terminals at each side of the array where the plurality of driving voltage terminals coupled to a plurality of source terminals and a plurality of body terminals, and a current source coupled to the drain terminal of at least one element in the array to measure a drain current by converting the drain current into corresponding voltage measurements.
Embodiments of the present invention provide a method of testing a transistor having a floating gate and an overlap capacitance between the floating gate and at least one of a first and a second terminal. The method may include applying a test voltage to the first terminal of the transistor, biasing a second terminal of the transistor, measuring an output voltage at the second terminal, and determining if the output voltage is within a predetermined range. The test voltage via the overlap capacitance may place the transistor into an active mode.
Embodiments of the present invention provide a device including an array of detection elements and a test circuit. Each element may include a field effect transistor having a floating gate, a first terminal, a second terminal, and an overlap capacitance between the floating gate and at least one of the first and second terminals. The testing circuit may include a driving voltage terminal coupled to at least one first terminal, a biasing current terminal coupled to at least one second terminal, and an output voltage measurement terminal coupled to the at least one second terminal.
Embodiments of the present invention relate to a system and method for testing ion-sensing devices such as an ISFET device. Typically, ISFETs sense changes in the chemical composition in micro-wells that are formed above the ISFET. Such chemical changes may be caused by chemical reaction in fluids contained in the micro-wells.
The ISFET 100 may include a floating gate with a micro-well above the floating gate. This micro-well may contain an oxide (or other materials) with surface sites that cause a specific ion species to bind, inducing a change in charge distribution, and causing a change in potential at the surface. This change in surface potential may then be detected by the ISFET and measured by a read circuit, and represents the amount of ions contained within the micro-well. It is in this way that each ISFET in an array (e.g., ISFET element array 210 of
The ISFET 100 may operate similar to a standard MOSFET device and may transition among a few operational regions. When the ISFET 100 is biased such that VGS−Vth is positive and greater than VDS, the transistor is in the triode region, which is also commonly referred to as the linear region. In the triode region, the current through the drain terminal 120, ID, may be defined as:
where μn in is a charge-carrier effective mobility coefficient, Cox is a gate oxide capacitance per unit area coefficient, W is a gate width, L is a gate length, VGS is a voltage between the gate and source terminals, Vth is the threshold voltage, and VDS is the voltage between the drain and source terminals. In the triode region, the transistor has ohmic behavior between the drain and source and the drain current does not saturate.
When VGS−Vth is positive and less than VDS, the ISFET 100 operates in the saturation region, which is also commonly referred to as the active region. In the saturation region, the current through the drain terminal 120, ID, may be defined as:
where μn is the charge-carrier effective mobility coefficient, Cox is the gate oxide capacitance per unit area coefficient, W is the gate width, L is the gate length, VGS is the voltage between the gate and source terminals, Vth is the threshold voltage, VDS is the voltage between the drain and source terminals, and λ the factor for channel length modulation.
The ISFET 100 also has a threshold voltage dependent on the bulk potential. The bulk potential is referred to as the body voltage at terminal 140 and may operate as a second gate. The body effect may be defined as:
VTN=VTO+γ(√{square root over (VSB+2ϕ)}−√{square root over (2ϕ)}) Body Effect Equation
where VTN is a threshold voltage with substrate bias present, VTO is a zero-VSB value of threshold voltage, VSB is a voltage between the source and body terminals, γ is a body effect parameter, and 2ϕ is a surface potential parameter.
The ISFET 100 may be placed in a pixel element, and the pixel element may be a part of an array.
The array 210 is typically large and thus the source resistance along the array may vary by the inherent resistance of the transistor well and connection to the source. In an embodiment of the present invention, the ISFET array 210 may be tested by strategically placing body and source connections access at different physical locations around the array. Resistance of the source connections may then be calibrated to determine an accurate representation of the desired floating gate voltage.
After the source connections are made, a first test may be performed (Step 320). In the first test, first test voltages may be forced (applied) through the array. The first test voltages may be applied at multiple sides of the device such as either end of the columns or either side of the rows in the array. For example, the first test voltages may be applied to each of the sides sequentially. The first test voltages may be applied to the body and source terminals of the connected ISFETs. The first test voltages may include an initial voltage sweep to identify a suitable operating (or bias) voltage to test the pixel array.
First test measurements corresponding to the first test may then be obtained (Step 330). The first test voltages may produce corresponding currents through each connected ISFET. The produced currents may then be measured. A range of different voltage and current measurements may be provided in the embodiments of the present invention. For example, source and drain voltages may be forced while setting the body to a bias voltage of either an analog supply voltage or analog ground (depending on whether the ISFET is a PMOS or NMOS device). The resultant drain current may then be measured by a current source converting the measured current into a corresponding voltage value. In another example, the body, in principle, may be set to a voltage between the analog supply voltage and analog ground. Further, all body terminals may be set to the same voltage in an ISFET array and, thus, all the ISFETS in the array may be similarly biased. Another test may characterize threshold voltage mismatches across the array.
Based on the first test voltage values and the corresponding measured currents, a resistance value for the source connections may be calculated (Step 340). For example, a resistance gradient for the source connections may be calculated showing the resistance relationship of the test voltages and measured currents.
After calculating a resistance value for the source connections, body and source connections relative to one side of the device (e.g., one end of the columns) may be established. A second test may then be performed (Step 350). In the second test, second test voltages and currents may be forced or applied through the array. The second test voltages may be a voltage sweep at different operating (or bias) voltage points. Hence, the body connection, which is a bias voltage, may be set accordingly. The second test voltages and currents may be a sweep of a range of voltages that will operate the ISFETs in a different operational mode as described above, such as triode mode and saturation mode. Further, the ISFETs may be operated in body effect mode by using the body terminal as a second gate.
Second test measurements corresponding to the second test may then be obtained (Step 360). In each iteration of forcing or applying the second test voltages and currents, different currents and voltages as seen on the array may be measured. For example, source and drain voltages may be forced while the body voltage ranges between the analog supply voltage and analog ground voltage. The produced drain currents may be measured by a current source that may convert the current into corresponding voltage values. Based on the forced and measured voltages and currents, the gate voltage of the ISFETs may be calculated (Step 370). Specifically, the operational equations of the different modes described above may be used to calculate the gate voltage based on the forced and measured voltages and currents. Thus, the gate voltage for each ISFET element may be calculated to determine if the ISFET is working properly.
In an embodiment, steps 350-370 may be repeated for one or more other sides of the device (such as, e.g., the opposite end of the column). In another embodiment, steps 350-370 may be repeated after increasing or decreasing the forced voltages and currents by a factor of, for example, two. The gate voltage may then be calculated from the adjusted voltage (the bias point). The increased or decreased iteration may also be repeated for one or more other sides of the device. Also, the increasing or decreasing iteration may be repeated multiple times, each time in which the forced voltages and currents are adjusted by some factor with each iteration. After all iterations are complete, the calculated gate voltages may be averaged together to obtain a more accurate representation of the ISFET gate voltage. The averaged gate voltage may then be compared to a desired threshold range to determine if each ISFET is working properly. Further, the location (e.g., X and Y column and row in the array), values for each ISFET gate voltage, and/or the working condition of each ISFET may be recorded in a register, for example. Additional circuitry may be provided to allow for programming and/or erasing of each pixel element where the floating gate voltage of each ISFET may be programmed and/or erased. In some embodiments, the program/erase capability may provide a higher level of fault detection coverage. However, the program/erase circuitry may operate on a higher voltage than other circuit components, and design techniques to isolate higher voltage circuits may need to be applied to ensure circuit components are not damaged.
In another embodiment, in addition to voltage and current, the temperature of the device may also be varied to modulate the threshold voltage of the ISFET element. By varying the temperature, alternate data points may be observed and used to calculate the gate voltage of the ISFET element.
Further, the circuitry for individual pixel elements may take a variety of different forms.
The dry testing embodiments of the present invention described above exploit the characteristics of a floating gate transistor to test the functionality of the floating gate transistor. Therefore, the operation of the device can be tested with little to no circuit overhead, and the array size can be optimized because additional test circuitry is not required in the array area. Moreover, embodiments of the present invention do not require liquid to fully test the array; therefore, possible contamination is avoided.
Although aspects of the present invention have been described in which an ISFET array may be tested without the use of liquids, aspects of the present invention may be employed in conjunction with the use of liquids for testing purposes. For example, liquids having a known pH may be applied before, during, or after the dry testing techniques described herein. Thus, dry testing techniques described herein may be used together with wet testing techniques, if desired.
Moreover, different embodiments of the present invention herein have been described using an ISFET. However, the present invention is not limited to ISFETs and may be applicable to other suitable floating gate transistor devices or other suitable chemically-sensitive transistors.
In another embodiment of the present invention, the parasitic capacitances coupled to the floating gate may be used to test the functionality of a floating gate transistor.
An ISFET may be formed, generally, using a self-aligned process. A polysilicon gate may be formed, and floating gate 612 may be formed on a gate oxide 615 or other suitable gate insulator. Source and drain implants may be made in several steps. Before a nitride spacer is applied, an LDD (lightly doped drain) implant may be made. The LDD implant diffuses a small distance under the gate to reduce the electric field and to reduce the negative aspects of transistor performance such as hot carriers. The LDD implant, along with a step of degenerative doped implantation, forms the drain 614 and the source 616. The drain 614 and source 616 may have partially overlapping portions 607, 608 arranged under respective portions of gate oxide 615. The overlapping portions 607, 608 are formed within their respective implants such that a portion of the implants are beneath the floating gate electrode creating a parasitic capacitance. A process parameter relating to size of the overlap portions may be adjusted to control the size of the overlap portion and their capacitance.
In an embodiment of the present invention, a floating gate transistor may be tested using the above-described parasitic capacitance without using a fluidic bias to operate the floating gate.
The voltage at the source (shown as VOUT in
If the source voltage VOUT is within an expected range of a normal distribution of the array, the pixel may be considered operational because the test determines that the floating gate transistor can produce a valid and measurable signal. However, if the measured signal is too high or too low as compared to the normal distribution, it may indicate that an excessive trapped charge may be present at the floating gate. Also, if the distribution of the measured values in the tested array is significantly wide, it may indicate a large non-uniformity of the individual pixel elements. Large non-uniformities are generally considered unreliable and, thus, the array may be unusable.
In another embodiment, the floating gate transistor test may be expanded to measure the gain of the pixel and/or to determine other pixel properties. Again, the test may be conducted without using a fluidic bias to operate the floating gate and, therefore, maintaining the integrity of the array.
In an embodiment, the drain voltage may be varied while measuring corresponding source voltages. The source biasing current may held constant while the drain voltage is varied. In a first step, a first voltage may be applied to the drain, for example 3V, and the source may be biased accordingly. In a second step, the drain voltage may be adjusted to a second voltage, for example 2.8V, while the bias current at the source is held constant from the first step. The corresponding source voltage may be measured. The difference in the drain voltage (200 mV in the example) couples to the floating gate because of the overlap capacitance CGD. The resulting source voltage may thus be a fraction of the drain voltage difference. The ratio of the measured value to the input voltage represents the pixel gain and may be used to ascertain other pixel properties of interest.
Several embodiments of the present invention are specifically illustrated and described herein. However, it will be appreciated that modifications and variations of the present invention are covered by the above teachings. In other instances, well-known operations, components and circuits have not been described in detail so as not to obscure the embodiments. It can be appreciated that the specific structural and functional details disclosed herein may be representative and do not necessarily limit the scope of the embodiments.
Those skilled in the art may appreciate from the foregoing description that the present invention may be implemented in a variety of forms, and that the various embodiments may be implemented alone or in combination. Therefore, while the embodiments of the present invention have been described in connection with particular examples thereof, the true scope of the embodiments and/or methods of the present invention should not be so limited since other modifications will become apparent to the skilled practitioner upon a study of the drawings, specification, and following claims.
Various embodiments may be implemented using hardware elements, software elements, or a combination of both. Examples of hardware elements may include processors, microprocessors, circuits, circuit elements (e.g., transistors, resistors, capacitors, inductors, and so forth), integrated circuits, application specific integrated circuits (ASIC), programmable logic devices (PLD), digital signal processors (DSP), field programmable gate array (FPGA), logic gates, registers, semiconductor device, chips, microchips, chip sets, and so forth. Examples of software may include software components, programs, applications, computer programs, application programs, system programs, machine programs, operating system software, middleware, firmware, software modules, routines, subroutines, functions, methods, procedures, software interfaces, application program interfaces (API), instruction sets, computing code, computer code, code segments, computer code segments, words, values, symbols, or any combination thereof. Determining whether an embodiment is implemented using hardware elements and/or software elements may vary in accordance with any number of factors, such as desired computational rate, power levels, heat tolerances, processing cycle budget, input data rates, output data rates, memory resources, data bus speeds and other design or performance constraints.
Some embodiments may be implemented, for example, using a computer-readable medium or article which may store an instruction or a set of instructions that, if executed by a machine, may cause the machine to perform a method and/or operations in accordance with the embodiments. Such a machine may include, for example, any suitable processing platform, computing platform, computing device, processing device, computing system, processing system, computer, processor, or the like, and may be implemented using any suitable combination of hardware and/or software. The computer-readable medium or article may include, for example, any suitable type of memory unit, memory device, memory article, memory medium, storage device, storage article, storage medium and/or storage unit, for example, memory, removable or non-removable media, erasable or non-erasable media, writeable or re-writeable media, digital or analog media, hard disk, floppy disk, Compact Disc Read Only Memory (CD-ROM), Compact Disc Recordable (CD-R), Compact Disc Rewriteable (CD-RW), optical disk, magnetic media, magneto-optical media, removable memory cards or disks, various types of Digital Versatile Disc (DVD), a tape, a cassette, or the like. The instructions may include any suitable type of code, such as source code, compiled code, interpreted code, executable code, static code, dynamic code, encrypted code, and the like, implemented using any suitable high-level, low-level, object-oriented, visual, compiled and/or interpreted programming language.
This application is a continuation of U.S. application Ser. No. 13/173,621 filed Jun. 30, 2011, which claims benefit of priority from U.S. Provisional Application No. 61/360,495 filed Jul. 1, 2010 and U.S. Provisional Application No. 61/360,493 filed Jun. 30, 2010, the disclosures of all of which are incorporated herein by reference in their entirety.
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Child | 15979439 | US |