Patent Grant
8455927
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 gage.
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.
However, traditionally, ion concentration in the analyte solution is measured by measuring an instantaneous voltage at an output of the ISFET. The signal-to-noise ratio provided by the instantaneous voltage may not be as high as desired in a lot of situations. Further, with the scaling of ISFET sensor array designs, more ISFET sensors are packed on a chip. Thus, there is a need in the art to provide a better SNR than the instantaneous voltage measurement and also a need for on-chip data compression.
Moreover, with the scaling of ISFET sensor array designs, more and more ISFET sensors are packed on a chip. Thus, there is a need in the art to provide a readout scheme to output measured data from a chip at a high speed.
A floating gate (FG) transistor may be used to detect ions in close proximity to the gate electrode. The transistor may be configured with other transistors to form a pixel that can be placed into an array for addressable readout. In the simplest form, the ancillary transistors are used solely to isolate and select the floating gate transistor for readout in an array. The floating gate transistor may be a chemically-sensitive transistor, and more specifically, a chemically-sensitive field effect transistor (ChemFET). The ChemFET may be designed with a metal-oxide-semiconductor field-effect transistor (MOSFET) containing self-aligned source and drain implants fabricated using standard complementary metal-oxide-semiconductor (CMOS) processing. The ChemFET may be an ion sensitive FET (ISFET), and may be a PMOS or an NMOS device.
To reduce the pixel size to the smallest dimensions and simplest form of operation, the ancillary transistors may be eliminated to form an ion sensitive field-effect transistor (ISFET) using one transistor. This one-transistor, or 1T, pixel can provide gain by converting the drain current to voltage in the column. Parasitic overlap capacitance between terminals of the transistor limits the gain. The capacitance ratios also allow consistent pixel-to-pixel gain matching and relatively constant current operation which justifies the use of a row selection line which can sink the necessary current without causing unacceptable variation. Derivatives of this allow for increased programmable gain through a cascoded transistor enabled during readout. Configurable pixels can be created to allow both common source read out as well as source follower read out.
Cgd may form between the gate G and the drain D. The pixel 100 may be addressable from the row line R, which supplies the column current (i.e., drain-to-source current of the transistor 101) and boosts the potential at the floating gate.
In a one-transistor pixel array, such as the one shown in
In one embodiment, the 1T ion pixel 100 may work by boot-strapping the row selection line R to the floating gate G while at the same time providing a source of current for the column line bias. In the simplest form, this bootstrapping occurs without adding any extra capacitors. The gate to drain overlap capacitance Cgd, as shown in
The operation of this pixel depends on the fact that the signal range of any given pixel is small compared to the supply voltage or read range of the source follower. For example, the useful signal range may be only 100 mV and the supply voltage may be 3.3V. When a row is selected, the R line is driven to an active high voltage VH, while all other row lines are held at an active low voltage VL. The voltage VL is selected to be approximately equal to the nominal voltage on the column line C during the readout of any given pixel. Because the signal range is small, this voltage is known to within 100 mV in this example. Therefore, the drain to source voltage of all inactive pixels is always held to small values. This point is only critical if the gate to source voltage of inactive pixels is near the threshold of the device. For the row driven to VH, the FG voltages for that row are significantly higher than the other rows because of the bootstrapping that occurs when the row line transitions to VH. After the column line switch Sb is open, the final value on the column line will be determined almost entirely by the active row because the circuit operates according to the winner take-all mode.
There are two sources of current from other rows that can distort the signal value (one that adds current and one that takes away current) and there must be enough bootstrapping available to successfully read pixels without significant interaction from the other rows that produce these sources. The analysis to determine how much bootstrapping is needed is as follows. By the time the pixel is sampled, the device has entered the subthreshold region of operation which has a transconductance slope, for example, of approximately 100 mV/decade. This means that for every 100 mV of change in gate voltage, the current changes by 10 times. In order to effectively read a single pixel, a criteria is set so that 99% of the current on the column line is attributable to the active row and only 1% is attributable to the inactive rows (distortion current). From here it can be determined how much bootstrapping is necessary. With only 2 rows in the pixel array, a 200 mV difference in the floating gate voltages is needed according to the subthreshold slope. Since a signal range of about 100 mV is also needed to be accounted for, the total requirement is about 300 mV. If there are 10 rows, there may be 10 times more contribution from inactive rows. Therefore an extra 100 mV is needed. If the array is increased to 100 rows, another 100 mV is needed. If the array is increased to 10^n rows, 300+100*n mV is needed. As an example, a 10000 (10^4) row pixel array only requires a total of 700 mV (300+100*4) of bootstrapping. This amount of bootstrapping can be achieved from the overlap capacitance of the gate and drain. If more capacitance is needed, extra coupling can be facilitated in the mask layout. The above analysis only applies to pixels contributing to the readout current.
Pixels can also take current away from the column line and sink it through the deactivated row lines. Since the deactivated row line is set to approximately the level of the column line, this current draw will be minimal but it must still be quantified and controlled. To accomplish this, the final current on the column line should not be allowed to diminish beyond a certain level. This is ensured by loading the column with a small current sink such as 1 uA. For a W/L (width to length) ratio of 1, a transistor biased at its threshold will have a saturation current of about 0.1 uA.
This current decreases by a factor of 10 for every 100 mV of reduction in gate to source voltage. If less than 1% contribution of current is required, the VGS of inactive pixels needs to be kept to 100+100*n mV below the threshold voltage where 10^n is the number of pixels in the row. Thus, for a 10000 row pixel array, VGS needs to be kept to 500 mV below threshold. A typical 3.3V NMOS transistor has a VT of 600 mV. Therefore, VGS should be less than 100 mV for inactive pixels. Assuming that the FG has a nominal voltage of 0V when the row (R) and column (C) lines are at 0V, this condition is met even as R and C couple to the FG. If the FG has a larger nominal voltage than 0V (for example, due to the trapped charge), more bootstrapping is necessary to cause the column line to reach a level within 100 mV of the FG. As long as the nominal FG voltage is sufficiently low, the second criteria for minimizing distortion current is not a limiting factor. Finally, enough bootstrapping is needed to produce a current on the column line that matches the bleeding current so that the pixel can produce a measurable voltage on the column line. If VG is nominally 0v, then 700 mV is needed for bootstrapping. Therefore, for an NMOS with VT as large as 600 mV, the amount of bootstrapping required is simply limited by the VT. In order to readout the pixel with margin, a good target for bootstrapping is 1V. This leaves 300 mV of range for variation. Achieving 1V of bootstrapping is practical within a 3.3V supply.
All the current from the column readout is distributed through the row line. This causes significant droop in the voltage of the row line if the column current is also significant. The voltage droop affects the bootstrapping level but is not detrimental to the readout of the source follower because variation in drain voltage has only a second order effect. Since pixels are read out with multiple samples, offsets are canceled such that the droop does not affect the sensitivity of the pixels.
It should be noted that the same layout can be used for both source follower readout and common source readout as long as optimizations are not made for either. Only accommodations that need to be made are in the column circuits. This makes for a flexible readout architecture and either readout method may be used depending on the necessary signal range. If the signal needs a high gain, the common source mode should be used. Otherwise, the source follower mode may be used.
The following analysis is given for the gain of the source follower readout. Referring to
In one embodiment, the present invention obtains voltage gain by reading out with the common source configuration. It is desirable to achieve both a reduction in pixel size as well as an increase in signal level. The present invention eliminates the ancillary transistors in other pixel designs (e.g., 2T and 3T discussed below) and uses the source of the ISFET as the selection line to achieve both of these goals. The common source mode is a gain mode and a current mode.
The schematic of an array of pixels with column readout switches according to one embodiment of the present invention is shown in
The pixel array can be loaded with a current source with finite output resistance or another load device such as a resistor. Normally the row selection lines will be held at an active high voltage VH. When a row is selected for readout, its row selection line is pulled low to VL. The value of VL is set such that the nominal current level is about 1 uA. If the FG has a value of 100 mV higher than the norm, 10 times this current will result on the column line. If the value of FG is 100 mV lower than the norm, the current will be 10 times lower. The settling time of the signal on the column line will be signal dependent. The voltage gain is achieved with the selection of the value of R and it can be configurable to achieve programmable gain. For example, if R is 100k ohms, then the 100 mV, translates to 1V at the output.
The actual circuit is more complicated than just a simple common source amplifier because of the parasitic capacitance involved. Since the FG node is not driven, but rather capacitively coupled to the output, there is a feedback mechanism that limits the gain. This limit is roughly equal to the total capacitance at the FG node to the gate to drain capacitance. This ratio may be about 3. It could be designed to achieve higher gain such as 10 times with careful mask operations to reduce source and drain extensions.
The overlap capacitance created by the LDD regions can be reduced by skipping the LDD implants at the drain for the device.
In the 1T pixel shown in
The pixel in common source readout configuration is shown in
Since A is large compared to the loop gain, the negative input terminal may be considered as a virtual ground node and the gain of the circuit may be determined as Vo/Vi=−Cc/Cgd. Since this ratio is known from the analysis or measured values of the source follower configuration, the gain may be determined to be about 6.5. However compared to the source follower, the gain is Vo/Vi=2/(Asf−G). In this example, a gain of 10 is realized over the source follower configuration. A lower bound on this gain is given by assuming that the input capacitance of the source follower is solely due to Cgd and that the Asf is equal to 1. In this case the gain is about 3. Since neither of these conditions is realistic, the gain is expected to always exceed this number. Thus, if the gain of the source follower configuration of a pixel is known, the gain of the common source configuration of this pixel is also known. In addition, the higher the gain, the more sensitive the pixel is. This makes the common source configuration preferable.
Flicker noise can be reduced by using a channel doping of the same type as the minority carrier. For example, an NMOS with a n-type implant produces a buried channel transistor. To shift the work function of the device, a P+ gate electrode can be used.
One derivative of the one-transistor pixel allows for increased programmable gain through a cascoded transistor enabled during readout.
Since the gain of the common source readout is limited by the Cgd capacitance, as shown in
Higher gain and variable gain may be produced in the 1T configuration by bringing the cascode device outside the pixel to the column line.
In this case, the cascode forces the drain of the pixel to remain at a fairly steady voltage over the range of inputs. This causes the pixel to push nearly all of the change in current through the cascode device at the base of the array and into the current load. This reduces the negative feedback from Cds, which would otherwise limit the gain. Given that the current load has infinite output resistance and there is effectively no coupling capacitor to the FG node, the gain of the pixel is now −(gmlrO1+1)gm2rO2, wherein gm1 is the transconductance of the cascode device at the base of the column line and gm2 is the transconductance of the pixel and rO1 and rO2 are the small signal output resistances as seen at the drain. The value of the output resistance is determined by channel length modulation. Longer gate lengths produce higher output resistance because the effect of channel length modulation is minimized. Since this gain is so large, it can be limited and configured by variation of the current source output resistance, which is shown as Radj in
Various layout choices can be made to implement a 1T and 2T transistor. In order to reduce the size of the pixel the source and drains of adjacent pixels can be shared. In this way a single row selection line enables 2 rows at a time. This reduces the row wiring: two columns are then read out at once for a given column pitch. Such a scheme is shown in
In one embodiment, the cascoded device is gain-enhanced with a differential amplifier in feedback to control a transistor that maintains a constant voltage on the column line.
In a pixel array, a row selection device may be used for selection and isolation.
When a row selection line is activated, the row selection device (a MOSFET) forms a channel due to the gate voltage exceeding a threshold voltage and acts like a switch. When the row selection is deactivated, the channel is diminished. It is important to note that a row selection device never really completely turns “on” or “off”. It only approximates a switch. When the gate is substantially lower than the source of the row selection transistor, good isolation is achieved and the pixel with the active row selection can be read effectively without input from deactivated pixels. With many rows in an array of pixels, it is necessary to achieve a given level of isolation for each row selection device. That is, the requirements for the row selection device depend on the number of rows.
Both ISFET 1101 and the row selection device 1102 are shown as NMOS, but other types of transistors may be used as well. The 2T pixel 1100 is configured as the source follower readout mode, although 2T pixels may be configured as the common source readout mode.
In
In
In
In
The right column, including a pixel consisting of 1405RS and 1405IS, a pixel consisting of 1406RS and 1406IS, a pixel consisting of 1407RS and 1407IS, and a pixel consisting of 1408RS and 1408IS, is coupled to column traces cb[2], ct[1], and cb[3] in substantially the same manner as described above.
The pixel array 1400 has high density because of continuous diffusion, shared contacts, mirrored pixels, and one ct (column top) line and 2 cb (column bottom) line per physical column. A global bulk contact may be implemented by using a P+ wafer with P− epitaxy region.
The arrangement of pixel array 1400 provides for high speed operation. Row lines rs[0] and rs[1] are selected together and readout through cb[0] and cb[1]. This leads to a 4 times faster readout due to twice the number of pixels enabled for a single readout and half the parasitic load of a continuous array, allowing each column to settle twice as fast. In an embodiment, the full array is separated into a top half and a bottom half. This leads to another 4 times faster readout time due to twice the number of pixels readout at a time (both out the top and the bottom) and half the parasitic load of a continuous array. Thus, the total increase in speed over a single row selected continuous array is 16 times.
In an embodiment, both top and bottom halves of the pixel array may be enabled at the same time during readout. This can allow a multiplexing of readout between the top half and the bottom half. For example, one half can be doing a “wash” (e.g., flushing out reactants from the wells over the pixel devices) and the other half can be performing the readout. Once the other half is read, the readout for the two halves is switched.
In an embodiment, a 2T pixel design can incorporate two chemically-sensitive transistors (e.g., ISFETs) rather than one chemically-sensitive transistor and one row select device as described with respect to
In one embodiment, a column circuit allows column lines to be swapped to a sampling circuit such that either source-side or drain-side row selection can be made in either source follower mode or common source mode.
One or more charge pumps may be used to amplify the output voltage from a chemically-sensitive pixel that comprises one or more transistors, such as those described above.
At time t0, all switches are off.
At time t1, φ1 switches 1501, 1502, 1503 and 1504 are turned on. The track phase may start. An input voltage Vin, which may be from an ion sensitive pixel, may start to charge capacitors 1507 and 1508.
At time t2, φ1 switches 1501, 1502, 1503 and 1504 are turned off, and capacitors 1507 and 1508 are charged to Vin−Vref1.
At time t3, φ2 switches 1505 and 1506 are turned on, while φ1 switches 1501, 1502, 1503 and 1504 remain off. The boost phase may start. The capacitor 1507 may start to discharge through the capacitor 1508. Since the capacitors are in parallel during the track phase and in series during the boost phase, and the total capacitance is halved during the boost phase while the total charge remains fixed, the voltage over the total capacitance must double, making Vout approximately two times Vin.
A source follower SF may be used to decouple the gain circuit from the following stage.
The charge pump 1500 may provide a two times gain without a noisy amplifier to provide a virtual ground.
At time t0, all switches are off.
At time t1, φ1 switches 1501, 1502, 1503, 1504, 1601 and 1602 are turned on. The track phase may start. An input voltage Vin, which may be from an ion sensitive pixel, may start to charge capacitors 1507, 1508 and 1604.
At time t2, φ1 switches 1501, 1502, 1503, 1504, 1601 and 1602 are turned off, and capacitors 1507, 1508 and 1604 are charged to Vin−Vref1.
At time t3, φ2 switches 1505 and 1603 are turned on, while φ1 switches 1501, 1502, 1503, 1504, 1601 and 1602 remain off. The boost phase may start. The capacitor 1507 may start to discharge through the capacitors 1508 and 1604, and the capacitor 1508 may start to discharge through the capacitor 1604. Since the capacitors are in parallel during the track phase and in series during the boost phase, and the total capacitance is divided by three during the boost phase while the total charge remains fixed, the voltage over the total capacitance must triple, making Vout approximately three times Vin.
Additional series charge pumps can be added to increase the gain further. In a multi-stage charge pump, the capacitor values do not have to be the same size from stage to stage. It can be observed that the total area consumed by capacitors increases with the square of the gain. Although this feature may, in some cases, be undesirable with respect to area usage, power consumption, and throughput, the charge pump can be used without these penalties when the total noise produced by the ion sensitive pixel and associated fluidic noise is larger than the charge pump KT/C noise when a reasonable capacitor size is used.
At time t0, all switches are off.
At time t1, a switch φsp is on, providing an input voltage Vin to the input of the charge pump 1500.
From time t2 to time t5, the charge pump 1500 operates to push the output voltage Vout to 2(Vin−Vref1), as described before with reference to
From time t6 to t7, the switch φfb is on, feeding the output voltage 2(Vin−Vref1). back to the input of the charge pump 1500, and the first cycle ends.
During the second cycle, the charge pump 1500 amplifies the output voltage by 2(2(Vin−Vref1)). The process repeats, with the output being amplified during each cycle.
An ion sensitive MOS electrode is charge coupled to adjacent electrodes to facilitate both confinement and isolation of carriers. Measurements of ion concentration are made by discrete charge packets produced at each pixel and confined by potential barriers and wells. The ion sensitive electrode can act as either a barrier level or as a potential well. Working in the charge domain provides several benefits, including but not limited to: 1) increased signal level and improved signal to noise through the accumulation of multiple charge packets within each pixel, 2) better threshold matching of the MOS sensing and reference structures, 3) reduction in flicker noise, and 4) global-snap shot operation.
A floating electrode is used to detect ions in close proximity to the electrode.
The electrode is charge coupled to other electrodes and to other transistors to form a pixel that can be placed into an array for addressable readout. It is possible to obtain gain by accumulating charge into another electrode or onto a floating diffusion (FD) node or directly onto the column line. It is desirable to achieve both a reduction in pixel size as well as increase in signal level. To reduce pixel size, ancillary transistors may be eliminated and a charge storage node with certain activation and deactivation sequences may be used.
The ion sensitive (IS) accumulation pixel contains some of the following concepts:
The basic IS accumulation pixel is shown in
The thermal noise can be reduced by half the power by following the reset operation with a subthreshold reset before sampling. In general, the thermal noise is low compared to the signal due to the charge accumulation. A correlated reset scheme with global shutter is available in other configurations.
The basic charge accumulation scheme is shown in
In alternative embodiments, the order of electrodes may be switched, and/or the
IS electrode may be used as the barrier rather than the well. Transistors may be added to this accumulation line to enable a large array of pixels. The ancillary transistors are used to increase speed. However, it should be noted that no transistors are necessary to enable a full pixel array of the accumulation line. Instead, an array can be partitioned such that no transistors are needed. In an embodiment, the FD nodes are connected to the column line. Before a pixel is read out, the column line is reset to VDD. Then a row is selected by accumulating charge for that row directly onto the column line. After many cycles, the column discharges to a value directly proportional to the ion concentration. Since the capacitance of the column line depends on the total number of rows, the amount of accumulation required, depends on the number of rows. The array can be partitioned into sub arrays to make timing scalable. For example, every 100 rows can contain a local source follower buffer that is then connected to a global array.
This hierarchical approach can be used in general with all readout schemes to make massive arrays of pixels with fast readout.
Due to the thermal activity of carriers, charge packets cannot be generated without noise. Each fill and spill operation produces charge error proportional to KTC (thermal noise in the floating diffusion capacitor), where C is equal to Cox times the area of the ion sensitive electrode. During the fill operation charge can flow freely between the source of electrons and the confinement well. However, during the spill operation, the device enters the subthreshold mode and carriers move by diffusion, mainly in only one direction, which results in half of the thermal noise of a resistive channel. The total noise in electrons for each charge packet is therefore sqrt(KTC/2)/q where q represents the charge of one electron in coulombs (1.6×10e-19). The signal in electrons is equal to VC/q. The signal to noise ratio after n cycles is equal to V*sqrt(2nC/KT). Note that the signal to noise ratio improves by the square root of the number of cycles of accumulation. For small signal levels, the amount of accumulation will be limited to the threshold mismatch between the VR reference electrode and the ion sensitive electrode. Since there is a reference electrode in every pixel and the electrodes are charge coupled, the relative threshold mismatch between each pair of electrodes is small. Assuming, this difference is about 1 mV, over 1000 accumulation cycles should be feasible, thereby improving the signal to noise by more than 30 times. By way of example, if the signal is 1 mV and the electrode area is 1 square micron with Cox=5fF/um^2, the signal to noise ratio after 1000 cycles is 50 to 1. Since the signal level then reaches 1V, it is expected that no other noise source is relevant. For clarity, the dominant noise is simply the charge packet thermal noise which is well known.
Several design permutations are available depending on the desired mode of operation. The CCD channels are surface mode and are built in standard CMOS technology preferably below 0.13 um. Extra implants can be added to avoid surface trapping and other defects. A channel stop and channel can be formed from donor and acceptor impurity implants. The channel can be made of multiple implants to produce a potential profile optimal for the mode of operation.
The three transistors are a reset transistor 2701, a source follower 2702 and a row selection switch 2703. The reset transistor 2701 has a gate controlled by a reset signal RST, a source coupled to the floating diffusion (FD) of a pixel, and a drain connected to a fixed voltage. The source follower 2702 has its gate connected to the source of the reset transistor 2701, and its drain connected to a fixed voltage. A row selection transistor 2703 has its gate connected to a row line, its drain connected to a fixed voltage and its source connected to a column. Other electrodes interacting with the pixel includes a transfer gate TG, an ion selective electrode ISE, an input control gate ICG, and an input diffusion ID. These three elements form charge coupled electrodes that are operated in an identical way to VS, VR, and TX in
The sample and hold circuit 2901 may include a switch SH, a switch CAL, a capacitor Csh, and an amplifier Amp. The switch SH's input is coupled to the output of the column buffer 2903, and its output is coupled to a voltage VREF through the switch CAL, the upper part of the capacitor Csh, and the input of the amplifier Amp. The amplifier is biased by a voltage VB2. The output of the amplifier is coupled to a switch 2904 controlled by a signal ColSeln from a column selection shift register. The output of the switch 2904 is buffered by an output buffer 2905 before reaching the output terminal Vout. The output buffer is biased by a voltage VB3.
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. For example, some embodiments are described with an NMOS. A skilled artisan would appreciate that a PMOS may be used as well.
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 claims the benefit of priority to previously filed U.S. provisional patent application Ser. No. 61/360,493 filed Jun. 30, 2010, U.S. provisional application Ser. No. 61/360,495 filed Jul. 1, 2010, U.S. provisional application Ser. No. 61/361,403 filed Jul. 3, 2010, and U.S. provisional application Ser. No. 61/365,327 filed Jul. 17, 2010, the disclosures of all of which are incorporated herein by reference in their entireties.
| Number | Name | Date | Kind |
|---|---|---|---|
| 4411741 | Janata | Oct 1983 | A |
| 4438354 | Haque et al. | Mar 1984 | A |
| 4490678 | Kuisl et al. | Dec 1984 | A |
| 4743954 | Brown | May 1988 | A |
| 4777019 | Dandekar | Oct 1988 | A |
| 4822566 | Newman | Apr 1989 | A |
| 4863849 | Melamede | Sep 1989 | A |
| 4864229 | Lauks et al. | Sep 1989 | A |
| 4874499 | Smith et al. | Oct 1989 | A |
| 4893088 | Myers et al. | Jan 1990 | A |
| 4971903 | Hyman | Nov 1990 | A |
| 5038192 | Bonneau | Aug 1991 | A |
| 5110441 | Kinlen et al. | May 1992 | A |
| 5138251 | Koshiishi et al. | Aug 1992 | A |
| 5142236 | Maloberti et al. | Aug 1992 | A |
| 5151759 | Vinal | Sep 1992 | A |
| 5164319 | Hafeman et al. | Nov 1992 | A |
| 5317407 | Michon | May 1994 | A |
| 5436149 | Barnes | Jul 1995 | A |
| 5439839 | Jang | Aug 1995 | A |
| 5466348 | Holm-Kennedy | Nov 1995 | A |
| 5475337 | Tatsumi | Dec 1995 | A |
| 5554339 | Cozzette et al. | Sep 1996 | A |
| 5593838 | Zanzucchi et al. | Jan 1997 | A |
| 5600451 | Maki | Feb 1997 | A |
| 5637469 | Wilding et al. | Jun 1997 | A |
| 5702964 | Lee | Dec 1997 | A |
| 5793230 | Chu et al. | Aug 1998 | A |
| 5846708 | Hollis et al. | Dec 1998 | A |
| 5894284 | Garrity et al. | Apr 1999 | A |
| 5911873 | McCarron et al. | Jun 1999 | A |
| 5922591 | Anderson et al. | Jul 1999 | A |
| 5923421 | Rajic et al. | Jul 1999 | A |
| 5958703 | Dower et al. | Sep 1999 | A |
| 5965452 | Kovacs | Oct 1999 | A |
| 6107032 | Kilger et al. | Aug 2000 | A |
| 6210891 | Nyren et al. | Apr 2001 | B1 |
| 6255678 | Sawada et al. | Jul 2001 | B1 |
| 6274320 | Rothberg et al. | Aug 2001 | B1 |
| 6327410 | Walt et al. | Dec 2001 | B1 |
| 6355431 | Chee et al. | Mar 2002 | B1 |
| 6361671 | Mathies et al. | Mar 2002 | B1 |
| 6403957 | Fodor et al. | Jun 2002 | B1 |
| 6406848 | Bridgham et al. | Jun 2002 | B1 |
| 6413792 | Sauer et al. | Jul 2002 | B1 |
| 6429027 | Chee et al. | Aug 2002 | B1 |
| 6432360 | Church | Aug 2002 | B1 |
| 6465178 | Chappa et al. | Oct 2002 | B2 |
| 6475728 | Martin et al. | Nov 2002 | B1 |
| 6482639 | Snow et al. | Nov 2002 | B2 |
| 6485944 | Church et al. | Nov 2002 | B1 |
| 6511803 | Church et al. | Jan 2003 | B1 |
| 6518024 | Choong et al. | Feb 2003 | B2 |
| 6518146 | Singh et al. | Feb 2003 | B1 |
| 6537881 | Rangarajan et al. | Mar 2003 | B1 |
| 6602702 | McDevitt et al. | Aug 2003 | B1 |
| 6605428 | Klinger et al. | Aug 2003 | B2 |
| 6613513 | Parce et al. | Sep 2003 | B1 |
| 6624637 | Pechstein | Sep 2003 | B1 |
| 6627154 | Goodman et al. | Sep 2003 | B1 |
| 6654505 | Bridgham et al. | Nov 2003 | B2 |
| 6682899 | Bryan et al. | Jan 2004 | B2 |
| 6700814 | Nahas et al. | Mar 2004 | B1 |
| 6780591 | Williams et al. | Aug 2004 | B2 |
| 6795006 | Delight et al. | Sep 2004 | B1 |
| 6806052 | Bridgham et al. | Oct 2004 | B2 |
| 6828100 | Ronaghi | Dec 2004 | B1 |
| 6831994 | Bridgham et al. | Dec 2004 | B2 |
| 6859570 | Walt et al. | Feb 2005 | B2 |
| 6888194 | Yoshino | May 2005 | B2 |
| 6919211 | Fodor et al. | Jul 2005 | B1 |
| 6939451 | Zhao et al. | Sep 2005 | B2 |
| 6953958 | Baxter et al. | Oct 2005 | B2 |
| 6969488 | Bridgham et al. | Nov 2005 | B2 |
| 6998274 | Chee et al. | Feb 2006 | B2 |
| 7033754 | Chee et al. | Apr 2006 | B2 |
| 7037687 | Williams et al. | May 2006 | B2 |
| 7049645 | Sawada et al. | May 2006 | B2 |
| 7060431 | Chee et al. | Jun 2006 | B2 |
| 7085502 | Shushakov et al. | Aug 2006 | B2 |
| 7087387 | Gerdes et al. | Aug 2006 | B2 |
| 7090975 | Shultz et al. | Aug 2006 | B2 |
| 7097973 | Zenhausern | Aug 2006 | B1 |
| 7105300 | Parce et al. | Sep 2006 | B2 |
| 7169560 | Lapidus et al. | Jan 2007 | B2 |
| 7190026 | Lotfi et al. | Mar 2007 | B2 |
| 7192745 | Jaeger | Mar 2007 | B2 |
| 7211390 | Rothberg | May 2007 | B2 |
| 7223540 | Pourmand et al. | May 2007 | B2 |
| 7226734 | Chee et al. | Jun 2007 | B2 |
| 7238323 | Knapp et al. | Jul 2007 | B2 |
| 7244559 | Rothberg et al. | Jul 2007 | B2 |
| 7244567 | Chen | Jul 2007 | B2 |
| 7264929 | Rothberg et al. | Sep 2007 | B2 |
| 7264934 | Fuller | Sep 2007 | B2 |
| 7265929 | Umeda et al. | Sep 2007 | B2 |
| 7276749 | Martin et al. | Oct 2007 | B2 |
| 7282370 | Bridgham et al. | Oct 2007 | B2 |
| 7291496 | Holm-Kennedy | Nov 2007 | B2 |
| 7297518 | Quake et al. | Nov 2007 | B2 |
| 7303875 | Bock et al. | Dec 2007 | B1 |
| 7317216 | Holm-Kennedy | Jan 2008 | B2 |
| 7323305 | Leamon et al. | Jan 2008 | B2 |
| 7335762 | Rothberg et al. | Feb 2008 | B2 |
| 7394263 | Pechstein et al. | Jul 2008 | B2 |
| 7455971 | Chee et al. | Nov 2008 | B2 |
| 7462512 | Levon et al. | Dec 2008 | B2 |
| 7465512 | Wright et al. | Dec 2008 | B2 |
| 7575865 | Leamon et al. | Aug 2009 | B2 |
| 7595883 | El Gamal et al. | Sep 2009 | B1 |
| 7608810 | Yamada | Oct 2009 | B2 |
| 7667501 | Surendranath et al. | Feb 2010 | B2 |
| 7695907 | Miyahara et al. | Apr 2010 | B2 |
| 7785790 | Church et al. | Aug 2010 | B1 |
| 7859029 | Lee et al. | Dec 2010 | B2 |
| 7888013 | Miyahara et al. | Feb 2011 | B2 |
| 7923240 | Su | Apr 2011 | B2 |
| 7932034 | Esfandyarpour et al. | Apr 2011 | B2 |
| 7948015 | Rothberg et al. | May 2011 | B2 |
| 8217433 | Fife | Jul 2012 | B1 |
| 8262900 | Rothberg et al. | Sep 2012 | B2 |
| 8264014 | Rothberg et al. | Sep 2012 | B2 |
| 8269261 | Rothberg et al. | Sep 2012 | B2 |
| 8293082 | Rothberg et al. | Oct 2012 | B2 |
| 8306757 | Rothberg et al. | Nov 2012 | B2 |
| 8313625 | Rothberg et al. | Nov 2012 | B2 |
| 8313639 | Rothberg et al. | Nov 2012 | B2 |
| 8317999 | Rothberg et al. | Nov 2012 | B2 |
| 20010024790 | Kambara et al. | Sep 2001 | A1 |
| 20020001801 | Fan et al. | Jan 2002 | A1 |
| 20020012930 | Rothberg et al. | Jan 2002 | A1 |
| 20020012933 | Rothberg et al. | Jan 2002 | A1 |
| 20020042059 | Makarov et al. | Apr 2002 | A1 |
| 20020042388 | Cooper et al. | Apr 2002 | A1 |
| 20020061529 | Bridgham et al. | May 2002 | A1 |
| 20020086318 | Manalis et al. | Jul 2002 | A1 |
| 20020094533 | Hess et al. | Jul 2002 | A1 |
| 20020117659 | Lieber et al. | Aug 2002 | A1 |
| 20020117694 | Migliorato et al. | Aug 2002 | A1 |
| 20020131899 | Kovacs | Sep 2002 | A1 |
| 20020132221 | Chee et al. | Sep 2002 | A1 |
| 20020137062 | Williams et al. | Sep 2002 | A1 |
| 20020168678 | Williams et al. | Nov 2002 | A1 |
| 20020172963 | Kelley et al. | Nov 2002 | A1 |
| 20020187515 | Chee et al. | Dec 2002 | A1 |
| 20030032052 | Hadd et al. | Feb 2003 | A1 |
| 20030044799 | Matson | Mar 2003 | A1 |
| 20030049624 | Shultz et al. | Mar 2003 | A1 |
| 20030054396 | Weiner | Mar 2003 | A1 |
| 20030064366 | Hardin et al. | Apr 2003 | A1 |
| 20030068629 | Rothberg et al. | Apr 2003 | A1 |
| 20030077615 | Bridgham et al. | Apr 2003 | A1 |
| 20030100102 | Rothberg et al. | May 2003 | A1 |
| 20030108867 | Chee et al. | Jun 2003 | A1 |
| 20030124599 | Chen et al. | Jul 2003 | A1 |
| 20030138809 | Williams et al. | Jul 2003 | A1 |
| 20030148301 | Aono et al. | Aug 2003 | A1 |
| 20030148344 | Rothberg et al. | Aug 2003 | A1 |
| 20030157504 | Chee et al. | Aug 2003 | A1 |
| 20030186262 | Cailloux | Oct 2003 | A1 |
| 20030194740 | Williams | Oct 2003 | A1 |
| 20030215857 | Kilger et al. | Nov 2003 | A1 |
| 20030224419 | Corcoran et al. | Dec 2003 | A1 |
| 20040012998 | Chien et al. | Jan 2004 | A1 |
| 20040023253 | Kunwar et al. | Feb 2004 | A1 |
| 20040049237 | Larson et al. | Mar 2004 | A1 |
| 20040079636 | Hsia et al. | Apr 2004 | A1 |
| 20040130377 | Takeda et al. | Jul 2004 | A1 |
| 20040134798 | Toumazou et al. | Jul 2004 | A1 |
| 20040136866 | Pontis et al. | Jul 2004 | A1 |
| 20040146849 | Huang et al. | Jul 2004 | A1 |
| 20040185484 | Costa et al. | Sep 2004 | A1 |
| 20040197803 | Yaku et al. | Oct 2004 | A1 |
| 20040207384 | Brederlow et al. | Oct 2004 | A1 |
| 20040235216 | Rhodes | Nov 2004 | A1 |
| 20040248161 | Rothberg et al. | Dec 2004 | A1 |
| 20050006234 | Hassibi | Jan 2005 | A1 |
| 20050009022 | Weiner et al. | Jan 2005 | A1 |
| 20050017190 | Eversmann et al. | Jan 2005 | A1 |
| 20050031490 | Gumbrecht et al. | Feb 2005 | A1 |
| 20050032075 | Yaku et al. | Feb 2005 | A1 |
| 20050032076 | Williams et al. | Feb 2005 | A1 |
| 20050042627 | Chakrabarti et al. | Feb 2005 | A1 |
| 20050058990 | Guia et al. | Mar 2005 | A1 |
| 20050062093 | Sawada et al. | Mar 2005 | A1 |
| 20050079510 | Berka et al. | Apr 2005 | A1 |
| 20050093072 | Bonges et al. | May 2005 | A1 |
| 20050106587 | Klapproth et al. | May 2005 | A1 |
| 20050119497 | Hong et al. | Jun 2005 | A1 |
| 20050130173 | Leamon et al. | Jun 2005 | A1 |
| 20050130188 | Walt et al. | Jun 2005 | A1 |
| 20050142033 | Glezer et al. | Jun 2005 | A1 |
| 20050156207 | Yazawa et al. | Jul 2005 | A1 |
| 20050181440 | Chee et al. | Aug 2005 | A1 |
| 20050191698 | Chee et al. | Sep 2005 | A1 |
| 20050212016 | Brunner et al. | Sep 2005 | A1 |
| 20050224346 | Holm-Kennedy | Oct 2005 | A1 |
| 20050227264 | Nobile et al. | Oct 2005 | A1 |
| 20050230271 | Levon et al. | Oct 2005 | A1 |
| 20050233318 | Chee et al. | Oct 2005 | A1 |
| 20050239132 | Klapprith | Oct 2005 | A1 |
| 20050266456 | Williams et al. | Dec 2005 | A1 |
| 20050282224 | Fouillet et al. | Dec 2005 | A1 |
| 20060024711 | Lapidus et al. | Feb 2006 | A1 |
| 20060040297 | Leamon et al. | Feb 2006 | A1 |
| 20060051807 | Fuller | Mar 2006 | A1 |
| 20060057604 | Chen et al. | Mar 2006 | A1 |
| 20060073513 | Chee et al. | Apr 2006 | A1 |
| 20060105373 | Pourmand et al. | May 2006 | A1 |
| 20060115857 | Keen | Jun 2006 | A1 |
| 20060121670 | Stasiak | Jun 2006 | A1 |
| 20060134633 | Chen et al. | Jun 2006 | A1 |
| 20060141474 | Miyahara et al. | Jun 2006 | A1 |
| 20060154399 | Sauer et al. | Jul 2006 | A1 |
| 20060166203 | Tooke et al. | Jul 2006 | A1 |
| 20060182664 | Peck et al. | Aug 2006 | A1 |
| 20060183145 | Turner | Aug 2006 | A1 |
| 20060197118 | Migliorato et al. | Sep 2006 | A1 |
| 20060199193 | Koo et al. | Sep 2006 | A1 |
| 20060205061 | Roukes | Sep 2006 | A1 |
| 20060216812 | Okada et al. | Sep 2006 | A1 |
| 20060219558 | Hafeman et al. | Oct 2006 | A1 |
| 20060228721 | Leamon et al. | Oct 2006 | A1 |
| 20060244147 | Lee et al. | Nov 2006 | A1 |
| 20060246497 | Huang et al. | Nov 2006 | A1 |
| 20060269927 | Lieber | Nov 2006 | A1 |
| 20070059741 | Kamahori et al. | Mar 2007 | A1 |
| 20070069291 | Stuber et al. | Mar 2007 | A1 |
| 20070087362 | Church et al. | Apr 2007 | A1 |
| 20070087401 | Neilson et al. | Apr 2007 | A1 |
| 20070092872 | Rothberg et al. | Apr 2007 | A1 |
| 20070099208 | Drmanac et al. | May 2007 | A1 |
| 20070099351 | Peters et al. | May 2007 | A1 |
| 20070109454 | Chou | May 2007 | A1 |
| 20070117137 | Jaeger | May 2007 | A1 |
| 20070138132 | Barth | Jun 2007 | A1 |
| 20070172865 | Hardin et al. | Jul 2007 | A1 |
| 20070212681 | Shapiro et al. | Sep 2007 | A1 |
| 20070217963 | Elizarov et al. | Sep 2007 | A1 |
| 20070231824 | Chee et al. | Oct 2007 | A1 |
| 20070252176 | Shim et al. | Nov 2007 | A1 |
| 20070262363 | Tao et al. | Nov 2007 | A1 |
| 20070278488 | Hirabayashi et al. | Dec 2007 | A1 |
| 20080003142 | Link et al. | Jan 2008 | A1 |
| 20080012007 | Li et al. | Jan 2008 | A1 |
| 20080014589 | Link et al. | Jan 2008 | A1 |
| 20080035494 | Gomez et al. | Feb 2008 | A1 |
| 20080096216 | Quake | Apr 2008 | A1 |
| 20080115361 | Santini et al. | May 2008 | A1 |
| 20080121946 | Youn et al. | May 2008 | A1 |
| 20080132693 | Berka et al. | Jun 2008 | A1 |
| 20080145910 | Ward et al. | Jun 2008 | A1 |
| 20080166727 | Esfandyarpour et al. | Jul 2008 | A1 |
| 20080176271 | Silver et al. | Jul 2008 | A1 |
| 20080213770 | Williams et al. | Sep 2008 | A1 |
| 20080230386 | Srinivasan et al. | Sep 2008 | A1 |
| 20080265985 | Toumazou et al. | Oct 2008 | A1 |
| 20080286762 | Miyahara et al. | Nov 2008 | A1 |
| 20080286767 | Miyahara et al. | Nov 2008 | A1 |
| 20090026082 | Rothberg et al. | Jan 2009 | A1 |
| 20090030117 | Lanphere et al. | Jan 2009 | A1 |
| 20090032401 | Ronaghi et al. | Feb 2009 | A1 |
| 20090048124 | Leamon et al. | Feb 2009 | A1 |
| 20090079414 | Levon et al. | Mar 2009 | A1 |
| 20090108831 | Levon et al. | Apr 2009 | A1 |
| 20090127589 | Rothberg et al. | May 2009 | A1 |
| 20090140763 | Kim | Jun 2009 | A1 |
| 20090143244 | Bridgham et al. | Jun 2009 | A1 |
| 20090156425 | Walt et al. | Jun 2009 | A1 |
| 20090170728 | Walt et al. | Jul 2009 | A1 |
| 20090273386 | Korobeynikow et al. | Nov 2009 | A1 |
| 20090316477 | Horiuchi | Dec 2009 | A1 |
| 20100007326 | Nakazato | Jan 2010 | A1 |
| 20100137143 | Rothberg et al. | Jun 2010 | A1 |
| 20100156454 | Weir | Jun 2010 | A1 |
| 20100188073 | Rothberg et al. | Jul 2010 | A1 |
| 20100197507 | Rothberg et al. | Aug 2010 | A1 |
| 20100255595 | Toumazou et al. | Oct 2010 | A1 |
| 20100282617 | Rothberg et al. | Nov 2010 | A1 |
| 20100300895 | Nobile et al. | Dec 2010 | A1 |
| 20100301398 | Rothberg et al. | Dec 2010 | A1 |
| 20110165557 | Ah et al. | Jul 2011 | A1 |
| 20110217697 | Rothberg et al. | Sep 2011 | A1 |
| 20110230375 | Rothberg et al. | Sep 2011 | A1 |
| 20110263463 | Rothberg et al. | Oct 2011 | A1 |
| 20110275522 | Rothberg et al. | Nov 2011 | A1 |
| 20110281737 | Rothberg et al. | Nov 2011 | A1 |
| 20110281741 | Rothberg et al. | Nov 2011 | A1 |
| 20110287945 | Rothberg et al. | Nov 2011 | A1 |
| 20120000274 | Fife | Jan 2012 | A1 |
| 20120001056 | Fife et al. | Jan 2012 | A1 |
| 20120001235 | Fife | Jan 2012 | A1 |
| 20120001236 | Fife et al. | Jan 2012 | A1 |
| 20120001237 | Fife et al. | Jan 2012 | A1 |
| 20120001615 | Levine et al. | Jan 2012 | A1 |
| 20120001646 | Bolander et al. | Jan 2012 | A1 |
| 20120001685 | Levine et al. | Jan 2012 | A1 |
| 20120013392 | Rothberg et al. | Jan 2012 | A1 |
| 20120022795 | Johnson et al. | Jan 2012 | A1 |
| 20120034607 | Rothberg et al. | Feb 2012 | A1 |
| 20120037961 | Rothberg et al. | Feb 2012 | A1 |
| 20120040844 | Rothberg et al. | Feb 2012 | A1 |
| 20120045844 | Rothberg et al. | Feb 2012 | A1 |
| 20120055811 | Rothberg et al. | Mar 2012 | A1 |
| 20120055813 | Rothberg et al. | Mar 2012 | A1 |
| 20120056248 | Fife | Mar 2012 | A1 |
| 20120129703 | Rothberg et al. | May 2012 | A1 |
| 20120129728 | Rothberg et al. | May 2012 | A1 |
| 20120129732 | Rothberg et al. | May 2012 | A1 |
| 20120135870 | Rothberg et al. | May 2012 | A1 |
| 20120168307 | Fife | Jul 2012 | A1 |
| 20120247977 | Rothberg et al. | Oct 2012 | A1 |
| 20120261274 | Rearick et al. | Oct 2012 | A1 |
| 20120265474 | Rearick et al. | Oct 2012 | A1 |
| 20120279859 | Rothberg et al. | Nov 2012 | A1 |
| 20120280285 | Rothberg et al. | Nov 2012 | A1 |
| 20120280286 | Rothberg et al. | Nov 2012 | A1 |
| 20120283146 | Rothberg et al. | Nov 2012 | A1 |
| 20120286332 | Rothberg et al. | Nov 2012 | A1 |
| 20120286333 | Rothberg et al. | Nov 2012 | A1 |
| 20120286771 | Rothberg et al. | Nov 2012 | A1 |
| 20120288853 | Rothberg et al. | Nov 2012 | A1 |
| 20120288976 | Rothberg et al. | Nov 2012 | A1 |
| 20120289413 | Rothberg et al. | Nov 2012 | A1 |
| 20120293158 | Rothberg et al. | Nov 2012 | A1 |
| 20120295795 | Rothberg et al. | Nov 2012 | A1 |
| 20120322054 | Rothberg et al. | Dec 2012 | A1 |
| 20120325683 | Milgrew | Dec 2012 | A1 |
| 20120326213 | Bustillo et al. | Dec 2012 | A1 |
| 20120326767 | Milgrew | Dec 2012 | A1 |
| 20120329043 | Milgrew | Dec 2012 | A1 |
| 20120329044 | Milgrew | Dec 2012 | A1 |
| 20120329192 | Bustillo et al. | Dec 2012 | A1 |
| 20130001653 | Milgrew | Jan 2013 | A1 |
| 20130004948 | Milgrew | Jan 2013 | A1 |
| 20130004949 | Rearick et al. | Jan 2013 | A1 |
| 20130009214 | Bustillo et al. | Jan 2013 | A1 |
| Number | Date | Country |
|---|---|---|
| 102203282 | Sep 2011 | CN |
| 0223618 | May 1987 | EP |
| 1371974 | Dec 2003 | EP |
| 1432818 | Jun 2004 | EP |
| 1542009 | Jun 2005 | EP |
| 2307577 | Apr 2011 | EP |
| 2457851 | Sep 2009 | GB |
| 2457851 | Sep 2009 | GB |
| 2461127 | Jul 2010 | GB |
| 2002272463 | Sep 2002 | JP |
| 2005-518541 | Jun 2005 | JP |
| 2011-525810 | Sep 2011 | JP |
| 10-0442838 | Jul 2004 | KR |
| 10-0455283 | Oct 2004 | KR |
| WO-8909283 | Oct 1989 | WO |
| WO-9813523 | Apr 1998 | WO |
| WO-9846797 | Oct 1998 | WO |
| WO-0120039 | Mar 2001 | WO |
| WO-0142498 | Jun 2001 | WO |
| WO-0181896 | Nov 2001 | WO |
| WO-02077287 | Oct 2002 | WO |
| WO-02086162 | Oct 2002 | WO |
| WO-03073088 | Sep 2003 | WO |
| WO-2004040291 | May 2004 | WO |
| WO-2005047878 | May 2005 | WO |
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| WO-2012003368 | Jan 2012 | WO |
| WO-2012003380 | Jan 2012 | WO |
| WO-2012006222 | Jan 2012 | WO |
| Entry |
|---|
| Van Kerkhof, J. , “The Development of an ISFET-based Heparin Sensor”, Thesis, 1994. |
| Ahmadian, A. et al., “Single-nucleotide polymorphism analysis by pyrosequencing”, Anal. Biochem, vol. 280, 2000, pp. 103-110. |
| Eijkel, J. , “Potentiometric detection and characterization of adsorbed protein using stimulus-response measurement techniques”, Thesis, Sep. 3, 1955, pp. 1-147; 160-192. |
| Hermon, Z. et al., “Miniaturized bio-electronic hybrid for chemical sensing applications”, Tech Connect News, Apr. 22, 2008, pp. 1. |
| Margulies, M. et al., “Genome sequencing in microfabricated high-density picolitre reactors”, Nature, vol. 437, 2005, pp. 376-380. |
| Marshall, A. et al., “DNA chips: an array of possibilities”, Nature Biotechnology, vol. 16 (Translation included), Jan. 1998, pp. 27-31. |
| Miyahara, Y. et al., “Biochip Using Micromatchining Technology”, J. Institute of Electrostatics, Japan, vol. 27(6), 2003, pp. 268-272. |
| Miyahara, Y. et al., “Potentiometric Detection of DNA Molecules Using Field Effect Transistor”, The Japan Society of Applied Physics, No. 3 (Translation included), 2003, pp. 1180, 30A-S2. |
| PCT/JP2005/001987 International Search Report Mailed Apr. 5, 2005. |
| PCT/JP2005/015522 International Search Report (includes English translation) Mailed Sep. 27, 2005. |
| PCT/US2011/042655 International Search Report Mailed Oct. 21, 2011, pp. 1-2. |
| PCT/US2011/042660 International Search Report Mailed Nov. 2, 2011. |
| Ronaghi, M. et al., “A Sequencing Method Based on Real-Time Pyrophosphate”, Science, vol. 281, Jul. 17, 1998, pp. 363-365. |
| Sakata, T. et al., “Potentiometric Detection of DNA Using Genetic Transistor”, Denki Gakkai Kenkyukai Shiryo Chemical Sensor Kenkyukai, CHS-03-51-55, 2003, pp. 1-5. |
| Shi, Y. et al., “Radical Capillary Array Electrophoresis Microplace and Scanner for High-Performance Nucleic Acid Analysis”, Anal. Chem., vol. 71, 1999, pp. 5354-5361. |
| Takenaka, S. et al., “DNA Sensing on a DNA Probe-Modified Electrode Using Ferrocenylnaphthalene Dimide as the Electrochemically Active Ligand”, Anal. Chem., vol. 72, 2000, pp. 1334-1341. |
| Van Kerkhof, J. “The Development of an ISFET-based Heparin Sensor”, Thesis, 1994. |
| Zhou, G. et al., “Quantitative detection of single nucleotide polymorphisms for a pooled sample by a bioluminometric assay coupled with modified primer extension reactions (BAMPER)”, Nuc. Acids Res., vol. 29(19), e93, 2001, pp. 1-11. |
| EP7867780.4 Examination Report Mailed Jul. 3, 2012. |
| Hideshima, S. et al., “Detection of tumor marker in blood serum using antibody-modified field effect transistor with optimized BSA blocking”, Sensors and Actuations B: Chemical, vol. 161, 2012, pp. 146-150. |
| Hijikata, M. et al., “Identification of a Single Nucleotide Polymorphism in the MXA Gene Promoter (T/T at nt-88) Correlated with the Response of Hepatitis C Patients to Interferon”, Intervirology, vol. 43, 2000, pp. 124-127. |
| Lee, C-S et al., “Ion-sensitive Field-Effect Transistor for Biological Sensing”, Sensors, vol. 9, 2009, pp. 7111-7131. |
| Ohno, Y. et al., “Electrolyte-Gated Graphene Field-Effect Transistors for Detecting pH and Protein Adsorption”, Nano Letters, vol. 9(9), Jul. 28, 2009, pp. 3318-3322. |
| Starodub, N. et al., “Immunosensor for the determination of the herbicide simazine based on an ion-selective field-effect transistor”, Analytica Chimica Acta, vol. 424, 2000, pp. 37-43. |
| Wang, W. et al., “Label-free detection of small-molecule-protein interactions by using nanowire nanosensors”, Proc. of the Natl. Acad.of Sciences (PNAS), vol. 102(9), 2005, pp. 3208-3212. |
| [No Author Listed], “ISFET Wikipedia article”, Wikipedia, Last modified Nov. 7, 2006. |
| Akiyama, T. et al., “Ion-Sensitive Field-Effect Transistors with Inorganic Gate Oxide for pH Sensing”, IEE Transactions on Electron Devices, vol. ED-20(12), 1982, pp. 1936-1941. |
| AU2011226767, “Search Information Statement”, Oct. 26, 2011, pp. 1-3. |
| Bandiera, L. et al., “A fully electronic sensor for the measurement of cDNA hybridization kinetics”, Biosens Bioelectron, vol. 22, 2007, pp. 2108-2114. |
| Barbaro, M. et al., “A Charge-Modulated FET for Detection of Biomolecular Processes: Conception, Modeling, and Simulation”, IEEE Transactions on Electron Devices, vol. 53(1), 2006, pp. 158-166. |
| Barbaro, M. et al., “A CMOS, Fully Integrated Sensor for Electronic Detection of DNA Hybridization”, IEEE Electron Device Letters, vol. 27(7), 2006, pp. 595-597. |
| Barbaro, M. et al., “Fully electronic DNA hybridization detection by a standard CMOS biochip”, Sensors and Actuators B Chemical, vol. 118, 2006, pp. 41-46. |
| Bashford, G. et al., “Automated bead-trapping apparatus and control system for single-molecule DNA sequencing”, Optics Express, vol. 16(5), Mar. 3, 2008, pp. 3445-3455. |
| Baumann, W. et al., “Microelectronic sensor system for microphysiological application on living cells”, Sensors Actuators B, vol. 55, 1999, pp. 77-89. |
| Bausells, J. et al., “Ion-sensitive field-effect transistors fabricated in a commercial CMOS technology”, Sensors and Actuators B Chemical, vol. 57, 1999, pp. 56-62. |
| Bergveld, I., “ISFET, Theory and Practice”, IEEE Sensor Conference, Toronto, Oct. 2003, pp. 1-26. |
| Bergveld, P., “Thirty years of ISFETOLOGY What happened in the past 30 years and what may happen in the next 30 years”, Sensors and Actuators B, vol. 88, 2003, pp. 1-20. |
| Besselink, G. et al., “ISFET Affinity Sensor”, Methods in Biotechnology, vol. 7: Affinity Biosensors: Techniques and Protocols, 1998, pp. 173-185. |
| Bobrov, P. et al., “Chemical sensitivity of an ISFET with Ta2O5 membrane in strong acid and alkaline solutions”, Sensors and Actuators B, vol. 3, 1991, pp. 75-81. |
| Bousse, L. et al., “A process for the combined fabrication of ion sensors and CMOS circuits”, IEEE Electron Device Letters, vol. 9(1), Jan. 1988, pp. 44-46. |
| Bousse, L. et al., “Zeta potential measurements of Ta2O5 and SiO2 thin films”, J. Colloid Interface Sci., vol. 147(1), Nov. 1991, pp. 22-32. |
| Chen et al., “Nanoscale field effect transistor for biomolecular signal amplification”, App Phys Letter, vol. 91, 2007, pp. 243511-1-243511-3. |
| Chen et al., “Silicon-based nanoelectronic field-effect pH sensor with local gate control”, App Phys Letter, vol. 89, 2006, pp. 223512-1-223512-3. |
| Chou, J. et al., “Letter to the Editor on Simulation of Ta2O5 gate ISFET temperature characteristics”, Sensors and Actuators B, vol. 80, 2001, pp. 290-291. |
| Chou, J. et al., “Simulation of Ta2O5 gate ISFET temperature characteristics”, Sensor and Actuators B, vol. 71, Letter to the Editor, 2000, pp. 73-61. |
| Chung, W-Y. et al., “ISFET interface circuit embedded with noise rejection capability”, Electronics Letters, vol. 40(18), e-pub ; 2 pages, 2004. |
| Chung, W-Y. et al., “ISFET performance enhancement by using the improved circuit techniques”, Sensors and Actuators B, vol. 113, 2006, pp. 555-562. |
| Eijkel, J. et al., “Measuring Donnan-related phenomena using a solid-state ion sensor and a concentration-step method”, J. Membrane Sci., vol. 127, 1997, pp. 203-221. |
| Eltoukhy, H. et al., “A 0.18um CMOS 10-6 lux Bioluminescence Detection System-on-Chip”, ISSCC 2004/Session12/Biomicrosystems/12.3, 2004, pp. 1-3. |
| Eltoukhy, H. et al., “A. 0.18-um CMOS Bioluminescence Detection Lab-on-Chip”, IEEE J Solid-State Circuits, vol. 41(3), 2006, pp. 651-662. |
| Eriksson, J. et al., “Pyrosequencing technology at elevated temperature”, Electrophoresis, vol. 25, 2004, pp. 20-27. |
| Esfandyarpour, H. et al., “Gate-controlled microfluidic chamber with magnetic bead for DNA sequencing-by-synthesis technology”, Proc 5th Intl Conf Nanochannels, Microchannels, Minnichannels, Puebla, Mexico (Jun. 18-20, 2007), pp. 1-5. |
| Eversmann, B. et al., “A 128×128 CMOS Biosensor Array for Extracellular Recording of Neural Activity”, IEEE J. Solid-State Circ., vol. 38(12), Dec. 12, 2003, pp. 2306-2317. |
| Faramarzpour, N. et al., “CMOS-Based Active Pixel for Low-Light Level Detection: Analysis and Measurements”, IEEE Trans Electron Devices, vol. 54(12), Dec. 2007, pp. 3229-3237. |
| Finn, A. et al., “Towards an Optimization of FET-Based Bio-Sensors”, European Cells and Materials, vol. 4, Sup 2, 2002, pp. 21-23. |
| Fraden, J., “Handbook of Modern Sensors—Physics, Designs, and Applications . . . ”, 17.3.2 CHEMFET Sensors, 1996, pp. 499-501. |
| Fritz, et al., “Electronic detection of DNA by its intrinsic molecular charge”, PNAS, vol. 99(22), 2002, pp. 14142-14146. |
| GB0811656.8, , “Search and Examination Report”, Mar. 12, 2010. |
| GB0811656.8, , “Search Report”, Sep. 21, 2009. |
| GB0811657.6, , “Examination Report”, Jun. 30, 2010. |
| GB0811657.6, , “Search Report under Section 17”, Oct. 26, 2009. |
| Gracia, I. et al., “Test Structures for ISFET Chemical Sensors”, Proc IEEE 1992 Intl Conf Microelec Test Struct, vol. 5, 1992, pp. 156-159. |
| Hammond, P. et al., “A System-on-Chip Digital pH Meter for Use in a Wireless Diagnostic Capsule”, IEEE Transactons on Biomedical Engineering, vol. 52(4), 2005, pp. 687-694. |
| Hammond, P. et al., “Design of a Single-Chip pH Sensor Using a Conventional 0.6-μm CMOS Process”, IEEE Sensors Journal, vol. 4(6), 2004, pp. 706-712. |
| Hammond, P. et al., “Encapsulation of a liquid-sensing microchip using SU-8 photoresist”, MicoElectronic Engineering, vol. 73-74, 2004, pp. 893 897. |
| Hammond, S. et al., “Genomic sequencing and analysis of a Chinese Hampster ovary cell line using Illumina sequencing technology”, BMC Genomics, 12:67, 2011, pp. 1-27. |
| Han, Y., “Label-free detection of biomolecules by a field-effect transistor microarray biosensor with bio-functionalized gate surfaces”, Masters Dissertation, 2006, pp. 1-63. |
| Hara, H. et al., “Dynamic response of a Ta205-gate pH-sensitive field-effect transistor”, Sensors Actuators B, vol. 32, 1996, pp. 115-119. |
| Hizawa, T. et al., “Fabrication of a two-dimensional pH image sensor using a charge transfer technique”, Sensors and Actuators B Chemical, 117, 2006, pp. 509-515. |
| Hizawa, T. et al., “32×32 pH Image Sensors for Real Time Observation of Biochemical Phenomena”, Transducers & Eurosensors '07, 14th International Conference on Solid-State, Actuators and Microsystems, Lyon, France, Jun. 10-14, 2007, pp. 1311-1312. |
| Jakobson, C. et al., “Low frequency noise and drift in Ion Senstive Field Effect Transistors”, Sensors Actuators B, vol. 68, 2000, pp. 134-139. |
| Ji, H. et al., “A CMOS contact imager for locating individual cells”, ISCAS, 2006, pp. 3557-3560. |
| Ji, H. et al., “Contact Imaging: Simulation and Experiment”, IEEE Trans Circuits Systems-I: Regular Papers, vol. 54(8), 2007, pp. 1698-1710. |
| Kim, D. et al., “An FET-type charger sensor for highly sensitive detection of DNA sequence”, Biosens Bioelectron, vol. 20(1), Jul. 30, 2004, pp. 69-74. |
| Klein, M., “Time effects of ion-sensitive field-effect transistors”, Sens Act B, vol. 17, 1989, pp. 203-208. |
| Koch, S. et al., “Protein detection with a novel ISFET-based zeta potential analyzer”, Biosensors & Bioelectronics, vol. 14, 1999, pp. 413-421. |
| Kruise, J. et al., “Detection of protein concentrations using a pH-step titration method”, Sensors Actuators B, vol. 44, 1997, pp. 297-303. |
| Leamon, J. et al., “A Massively Parallel PicoTiterPlate Based Platform for Discrete Picoliter-Scale Polymerase Chain Reactions”, Electrophoresis, vol. 24, Nov. 24, 2003, pp. 3769-3777. |
| Leamon, J. et al., “Cramming More Sequening Reactions onto Microreactor Chips”, Chemical Reviews, 107:, 2007, pp. 3367-3376. |
| Li, et al., “Sequene-Specifc Label-Free DNA Sensors Based on Silico Nanowires”, Nano Letters,, vol. 4(2), 2004, pp. 245-247. |
| Lohrengel, M. et al., “A new microcell or microreactor for material surface investigations at large current densities”, Electrochimica Acta, vol. 49, 2004, pp. 2863-2870. |
| Lui, A. et al., “A Test Chip for ISFET/CMNOS Technology Development”, Prooceedings of the 1996 IEEE International Conference on Microelectronic Test Structures, vol. 9, 1996, pp. 123-128. |
| Martinoia, S. et al., “A behavioral macromodel of the ISFET in SPICE”, Sensors Actuators B, vol. 62, 2000, pp. 182-189. |
| Martinoia, S., “Development of ISFET Array-Based Microsystems for Bioelectrochemical measurements of cell populations”, Biosensors & Bioelectronics, vol. 16, 2001, pp. 1043-1050. |
| Medoro, G. et al., “A Lab-on-a-Chip for Cell Detection and Manipulation”, IEEE Sensors J, vol. 3(3), 2003, pp. 317-325. |
| Meyburg, S. et al., “N-Channel field-effect transistors with floating gates for extracellular recordings”, Biosens Bioelectron, vol. 21(7), Jan. 15, 2006, pp. 1037-1044. |
| Milgrew, M. et al., “A large transistor based sensor array chip for direct extracellular imaging”, Sensors and Actuators B Chemical, vol. 111-112, 2005, pp. 347-353. |
| Milgrew, M. et al., “Microsensor Array Technology for Direct Extracellular Imaging”, Apr. 5, 2006, pp. 1-23. |
| Milgrew, M. et al., “The development of scalable sensor arrays using standard CMOS technology”, Sensors and Actuators B, 103, 2004, pp. 37-42. |
| Milgrew, M. et al., “The fabrication of scalable multi-sensor arrays using standard CMOS technology”, 2003 IEEE Custom Integrated Circuits Conference, 2003, pp. 513-516. |
| Milgrew, M. et al., “A 16×16 CMOS proton camera array for direct extracellular imaging of hydrogen-ion activity”, IEEE Intl Solid-State Circuits Conf, Session 32:24, 2008, pp. 590-591; 638. |
| Milgrew, M. et al., “Matching the transconductance characteristics of CMOS ESFET arrays by removing trapped charge”, IEEE Trans Electron Devices, vol. 55(4), 2008, pp. 1074-1079. |
| Miyahara, Y. et al., “Direct Transduction of Primer Extension into Electrical Signal Using Genetic Field Effect Transistor”, Micro Total Analysis Systems 2004, vol. 1, Proceedings of uTAS 2004, 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Malmo, Sweden, Sep. 26-30, 2004, pp. 303-305. |
| Nyren, P. et al., “Enzymatic Method for Continuous Monitoring of Inorganic Pyrophosphate Synthesis”, Analytical Biochemistry, vol. 151, 1985, pp. 504-509. |
| Oelbner, W. et al., “Encapsulation of ESFET sensor chips”, Sensors Actuators B, vol. 105, 2005, pp. 104-117. |
| Oelbner, W. et al., “Investigation of the dynamic response behaviour of ISFET pH sensors by means of laser Doppler velocimetry (LDV)”, Sensors Actuators B, vol. 26-27, 1995, pp. 345-348. |
| Offenhausser, A. et al., “Field-Effect transistor array for monitoring electrical activity from mammalian neurons in culture”, Biosensors & Bioelectronics, vol. 12(8), 1997, pp. 819-826. |
| Patolsky, F. et al., “Nanowire-Based Biosensors”, Analyt Chem 1, vol. 78(13), 2006, pp. 4261-4269. |
| PCT/US/2009/05745, “International Preliminary Report on Patentability”, 2009. |
| PCT/US/2009/05745, “International Search Report”, 2009. |
| PCT/US/2009/05745, “Written Opinion”, 2009. |
| PCT/US10/48835, “International Search Report and Written Opinion” Mailed Dec. 16, 2010. |
| PCT/US2007/025721, “Declaration of Non-Establishment of International Search Report”, Jul. 15, 2008. |
| PCT/US2007/025721, “International Prelimary Report on Patentability”, Jun. 16, 2009. |
| PCT/US2007/025721, “Written Opinion”, Jun. 16, 2009. |
| PCT/US2009/003766, “International Preliminary Report on Patentability”, Jan. 5, 2011. |
| PCT/US2009/003766, “International Search Report”, Apr. 8, 2010. |
| PCT/US2009/003766, “Written Opinion”, Apr. 8, 2010. |
| PCT/US2009/003797, “International Search Report”, Mar. 12, 2010. |
| PCT/US2009/003797, “Written Opinion”. |
| PCT/US2010/001543, “International Preliminary Report on Patentability”, Nov. 29, 2011, pp. 1-8. |
| PCT/US2010/001543, “International Search Report and Written Opinion”, Oct. 13, 2010, pp. 1-12. |
| PCT/US2010/001553, “International Search Report”, Jul. 28, 2010, pp. 1-2. |
| PCT/US2010/001553, Interntional Preliminary Report on Patentability,Dec. 8, 2011, pp. 1-10. |
| PCT/US2010/001553, “Written Opinion”, Jul. 14, 2010, pp. 1-6. |
| PCT/US2011/042665, “International Search Report”, Mailed Nov. 2, 2011. |
| PCT/US2011/42669, “International Search Report”, Jan. 9, 2012, pp. 1-5. |
| PCT/US2011/42669, “Written Opinion”, Jan. 9, 2012, pp. 1-5. |
| PCT/US2011/42683, “International Search Report”, Feb. 16, 2012. |
| PCT/US2011/42683, “Written Opinon”, Feb. 16, 2012. |
| Poghossian, A. et al., “Functional testing and characterization of ISFETs on wafer level by means of a micro-droplet cell”, Sensors, vol. 6, 2006, pp. 397-404. |
| Pourmand, N. et al., “Direct electrical detection of DNA synthesis”, PNAS, vol. 103(17), 2006, pp. 6466-6470. |
| Pouthas, F. et al., “Spatially resolved electronic detection of biopolymers”, Phys Rev, vol. 70, 2004, pp. 031906-1-031906-8. |
| Premanode, B. et al., “A composite ISFED readout circuit employing current feedback”, Sensors Actuators B, vol. 127, 2007, pp. 486-490. |
| Premanode, B. et al., “A novel, low power biosensor for real time monitoring of creatine and urea in peritoneal dialysis”, Sensors Actuators B, vol. 120, 2007, pp. 732-735. |
| Premanode, B. et al., “Ultra-low power precision ISFET readout using global current feedback”, Electronic Lett, vol. 42(22), Oct. 26, 2006, 2 pages. |
| Purushothaman, S. et al., “Towards Fast Solid State DNA Sequencing”, IEEE ISCAS 2002 Proceedings, 2002, pp. IV-169-IV-172. |
| Purushothaman, S. et al., “Protons and single nucleotide polymorphism detection: A simple use for the Ion Sensitive Field Effect Transistor”, Sensors and Actuators B Chemical, vol. 114, 2006, pp. 964-968. |
| Rodriguez-Villegas, E., “Solution to trapped charge in FGMOS transistors, vol. 39(19)”, Electronics Letters , 2003. |
| Sakata, T. et al., “Cell-based field effect devices fo cell adhesion analysis”, International Conference on Microtechnolodies in Medicine and Biology, May 9-12, 2006, Okinawa, Japan, pp. 177-179. |
| Sakata, T. et al., “Detection of DNA recognition events using multi-well field effect transistor”, Biosensors and Bioelectronics vol. 21, 2005, pp. 827-832. |
| Sakata, T. et al., “Detection sensitivity of genetic field effect transistor combined with charged nanoparticle-DNA conjugate”, Proceedings of 2006 International Conference on Microtechnologies in Medicine and Biology, May 9-12, 2005, Okinawa, Japan, 2006, pp. 97-100. |
| Sakata, T. et al., “Direct detection of single nucleotide polymorphism using genetic field effect transistor”, Digest of Papers Microprocesses and Nanotechnology 2004, Osaka, Japan, 2004 International Microprocesses and Nanotechnology Conference, 2004, pp. 226-227. |
| Sakata, T. et al., “Direct Detection of Single-Base Extension Reaction Using Genetic Field Effect Transistor”, Proceedings of 3rd Annual International IEEE EMBS Special Topic Conference on Microtechnologies in Medicine and Biology, Kahuku, Oahu, HI, May 12-15, 2005, pp. 219-222. |
| Sakata, T. et al., “Direct transduction of allele-specific primer extension into electrical signal using genetic field effect transistor”, Biosensors and Bioelectronics vol. 22, 2007, pp. 1311-1316. |
| Sakata, T. et al., “DNA Analysis Chip Based on Field-Effect Transistors”, Japanese Journal of Applied Physics, vol. 44, No. 4B, 2005, pp. 2854-2859. |
| Sakata, T. et al., “DNA Sequencing Based on Intrinsic Molecular Charges”, Angewandte Chemie International Edition, 2006, vol. 45, pp. 2225-2228. |
| Sakata, T. et al., “DNA Sequencing Based on Intrinsic Molecular Charges”, Angewandte Chemie International Edition, 2006, vol. 118, pp. 2283-2286. |
| Sakata, T. et al., “DNA Sequencing Using Genetic Field Effect Transistor”, 13th International Conference on Solid-State Sensors, Actuators and Microsystems, Jun. 5-9, 2005, Seoul, Korea, pp. 1676-1679. |
| Sakata, T. et al.,“Immobilization of oligonucleotide probes on Si3N4 surface and its application to genetic field effect transistor”, Materials Science and Engineering: C, vol. 24, 2004, pp. 827-832. |
| Sakata, T. et al., “Potential Behavior of Biochemically Modified Gold Electrode for Extended-Gate Field-Effect Transistor”, Japanese Journal of Applied Physics, vol. 44, No. 4B, 2005, pp. 2860-2863. |
| Sakata, T. et al., “Potential Response of Genetic Field Effect Transistor to Charged Nanoparticle-DNA Conjugate”, Digest of Papers Microprocesses and Nanotechnology 2005, 2005 Intl Microprocesses and Nanotech Conference, Tokyo, Japan, pp. 42-43. |
| Sakata et al., “Potentiometric Detection of Allele Specific Oligonucleotide Hybridization Using Genetic Field Effect Transistor”, Micro Total Anslysis Systems 2004, vol. 1, 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Sep. 26-30, 2004, Malmo, Sweden, pp. 300-302. |
| Sakata, T. et al., “Potentiometric Detection of DNA Molecules Hybridization Using Gene Field Effect Transistor and Intercalator”, Materials Research Society Symposium Proceedings, vol. 782, Micro- and Nanosystems, Dec. 1-3, 2003, Boston, Massachusetts, 2004, pp. 393-398. |
| Sakata, T. et al., “Potentiometric Detection of Single Nucleotide Polymorphism by Using a Genetic Field-effect transistor”, ChemBioChem 2005, vol. 6, 2005, pp. 703-710. |
| Sakurai, T. et al., “Real-Time Monitoring of DNA Polymerase Reactions by a Micro ISFET pH Sensor”, Anal Chem, vol. 64(17), 1992, pp. 1996-1997. |
| Salama, K., “CMOS luminescence detection lab-on-chip: modeling, design, and characterization”, Thesis, Presented at Stanford University, 2005, pp. ii-78. |
| Salama, K., “Modeling and simulation of luminescence detection platforms”, Biosensors & Bioelectronics, 2004, pp. 1377-1386. |
| Sawada, K. et al., “A novel fused sensor for photo- and ion-sensing”, Sensors Actuators B, vol. 106, 2005, pp. 614-618. |
| Sawada, K. et al., “Highly sensitive ion sensors using charge transfer technique”, Sensors Actuators B, vol. 98, 2004, pp. 69-72. |
| Schasfoort, B. et al., “Field-effect flow control for microfabricated fluidic networks”, Science, vol. 286(5441), Oct. 29, 1999, pp. 942-945. |
| Schasfoort, B. et al., “A new approach to immunoFET operation”, Biosensors & Bioelectronics, vol. 5, 1990, pp. 103-124. |
| Schoning, M. et al., “Bio FEDs (Field-Effect Devices): State-of-the-Art and New Directions”, Electroanalysis, vol. 18(19-20), 2006, pp. 1893-1900. |
| SG200903992-6, , “Search and Examination Report (Favourable) Mailed Jan. 20, 2011”, 12. |
| Shah, N., “Microfabrication of a parellel-array DNA pyrosequencing chip”, NNIN REU Research Accomplishments, 2005, pp. 130-131. |
| Shepherd, L. et al., “Towards direct biochemical analysis with weak inversion ISFETS”, Intl Workshop on Biomedical . . . , 2004, S1.5-5-S1.5-8. |
| Shepherd, L. et al., “A biochemical translinear principle with weak inversion ISFETs”, IEEE Trans Circuits Syst-I, vol. 52(12), Dec. 2005, pp. 2614-2619. |
| Shepherd, L. et al., “A novel voltage-clamped CMOS ISFET sensor interface”, IEEE, 2007, pp. 3331-3334. |
| Shepherd, L. et al., “Weak inversion ISFETs for ultra-low power biochemical sensing and real-time analysis”, Sensors Actuators B, vol. 107, 2005, pp. 468-473. |
| Simonian, et al., “FET bases biosensors for the direct detection of organophosphate neurotoxins”, Electroanalysis, vol. 16(22), 2004, pp. 1896-1906. |
| Souteyrand, E. et al., “Direct detection of the hybridization of synthetic homo-oligomer DNA sequences by field effect”, J Phys Chem B, vol. 101(15), 1997, pp. 2980-2985. |
| Tomaszewski, D. et al., “Electrical characterization of ISFETs”, J Telecomm Info Technol, Mar. 2007, pp. 55-60. |
| Toumazou, C. et al., “Using transistors to linearase biochemistry”, Electronics Letters, vol. 43(2), Jan. 18, 2007, 3 pages. |
| Truman, P., “Monitoring liquid transport and chemical composition in lab on . . . ”, Lab on a Chip, 2006, pp. 1220-1228. |
| Uslu, F. et al., “Labelfree fully electronic nucleic acid detection system based on a field-effect transistor device”, Biosens & Bioelectron, vol. 19(12), 2004, pp. 1723-1731. |
| Van Der Wouden, E. et al., “Directional flow induced by synchronized longitudinal and zeta-potential controlling AC-electrical fields”, Lab Chip, vol. 6(10), 2006, pp. 1300-1305. |
| Van Hal, R.E.G. et al., “A general model to describe the electrostatic potential at electrolyte oxide interfaces”, Advances in Colloid and Interface Science, vol. 69, 1996, pp. 31-62. |
| Van Kerkhof, J. et al., “The ISFET based heparin sensor with a monolayer of protamine as affinity ligand”, Biosensors & Bioelectronics, vol. 10(3), 1995, pp. 269-282. |
| Van Kerkhof, J. et al., “ISFET Responses on a stepwise change in electrolyte concentration at constant pH”, Sensors Actuators B: Chemical, vol. 18-19, Mar. 1994, pp. 56-59. |
| Wagner, T. et al., ““All-in-one” solid-state device based on a light-addressable potentiometric sensor platform”, Sensors and Actuators B, vol. 117, 2006, pp. 472-479. |
| Woias, P. ,“Modelling the short time response of ISFET sensors”, Sensors and Actuators B, vol. 24-25, 1995, pp. 211-217. |
| Woias, P. et al., “Slow pH response effects of silicon nitride ISFET sensors”, Sensors and Actuators B, vol. 48, 1998, pp. 501-504. |
| Wu, P. et al., “DNA and protein microarray printing on silicon nitride waveguide surfaces”, Biosensens Bioelectron, vol. 21(7), 2006, pp. 1252-1263. |
| Xu, J-J. et al., “Analytical Aspects of FET-Based Biosensors”, Frontiers in Bioscience, 10, 2005, pp. 420-430. |
| Yeow, T.C.W., “A very large integrated pH-ISFET sensor array chip compatible with standard CMOS processes”, Sensor and Actuators B, vol. 44, 1997, pp. 434-440. |
| Yuqing, M. et al., “Ion sensitive field effect trnasducer-based biosensors”, Biotechnology Advances, vol. 21, 2003, pp. 527-534. |
| Zhang, X. et al., “32-Channel Full Customized CMOS Biosensor Chip for Extracellular neural Signal Recording”, Proceedings of the 2nd International IEEE EMBs Conference on Neural Engineering, Arlington, VA-, 2005, pp. v-viii. |
| Number | Date | Country | |
|---|---|---|---|
| 20120001236 A1 | Jan 2012 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61360493 | Jun 2010 | US | |
| 61360495 | Jul 2010 | US | |
| 61361403 | Jul 2010 | US | |
| 61365327 | Jul 2010 | US |
