Field imager
A detection apparatus for detecting the presence of a sample, the detection apparatus comprising a chamber, ports for introducing a sample within the chamber, an actuation unit for establishing a controllable electromagnetic field in the chamber; and a sensing unit for sensing changes in the electromagnetic field due to the presence of the sample within the chamber. The sensing unit comprises a sensor device comprising a source and a drain embedded in a FET a gate for the FET, in which the gate is formed of a material whose conductivity is related to the electromagnetic field established in a nonconductive medium in contact with the gate.
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The behavior of matter in electrical or magnetic field, especially nonuniform fields, is of interest to scientists of various branches: Physics, chemistry, engineering, or life sciences. To chemists and physicists, it's a science of many and varied phenomena. To engineers, it's a source of new and useful techniques for separating, levitating, and rotating materials or improving material behavior.
In recent decades, Dielectrophoresis has become a fairly well known phenomenon in which a spatially nonuniform electric field exerts a net force on the field-induced dipole of a particle. Particles with higher polarizability than the surrounding medium experience positive dielectrophoresis and they move toward regions of highest electric field concentration. Particles less polarizable than the surrounding medium experience negative dielectrophoresis, and move towards regions of low electric field concentration. The force depends on the induced dipole and the electric field gradient, not on the particle's charge. Thus, dielectrophoresis has been used to precipitate DNA and proteins, to manipulate viruses (100 nm diameter), and to manipulate and separate cells and subcellular components such as microtubules.
Dielectrophoretic levitation fulfills a somewhat specialized need among the scientific and technical applications for dielectrophoresis. Two types of levitation, passive and feedback-controlled may be used to levitate particles exhibiting, respectively, negative and positive DEP behavior.
DEP is technologically important in its own right, as evidenced by the number of applications in such scientific and technical fields as biophysics, bioengineering, and mineral separation. As an example, which is important in cancer treatment, is cell fusion, as discussed by P. T. Gaynor, and P. S. Bodger in “Electrofusion processes: theoretical evaluation of high electric field effects on cellular transmembrane potentials”, IEE Proceedings-Science, Measurement and Technology, vol. 142, no. 2, pp. 176-182, 1995. In this process, the nonuniform electric field collects some fraction of these cells on electrode surfaces where cells of the two types inevitably encounter each other and form chains. A serious of short DC pulse is then applied to the electrodes. The strong DC field disturbs the membranes in the region of contact between cells and initiates their merge or fusion. A potential application of this technique is the production of antibodies useful in cancer research and treatment.
Lab-on-a-chip based on DEP phenomenon has become one of the hottest areas of research recently. It has many applications in the biological, pharmaceutical, medical, and environmental fields. These applications are characterized by complex experimental protocols, which need both microorganism detection and manipulation. Hence, lab-on-a-chip technology needs to integrate functions such as: actuation, sensing, and processing to increase their effectiveness. On the other hand, lab-on-a-chip technology holds the promise of cheaper, better and faster biological analysis. However, to date there is still an unmet need for lab-on-a-chip technology to effectively deal with the biological systems at the cell level.
Recently, two different lab-on-a-chip approaches have been proposed by G. Medoro, N. Manaresi, M. Tartagni, and R. Guerrieri, in “CMOS-only Sensors and Manipulation for microorganisms”, Proc. IEDM, pp. 415-418, 2000 and by N. Manaresi, A. Romani, G. Medoro, L. Altomare, A. Leonardi, M. Tartagni, and R. Guerrieri in “A CMOC Chip for Individual Manipulation and Detection”, IEEE International Solid-State Circuits Conference, ISSCC 03, pp. 486-488. 2003. The first, which was proposed in 2002, is the first lab-on-a-chip approach for electronic manipulation and detection of microorganisms. The proposed approach combines dielectrophoresis with impedance measurements to trap and move particles while monitoring their location and quantity in the device. The prototype has been realized using standard printed circuit board (PCB) technology. The sensing part in this approach can be performed by any electrode by switching from the electrical stimulus to a transimpedance amplifier, while all the other electrodes are connected to ground. The second lab-on-a-chip, which was proposed in 2003, is a microsystem for cell manipulation and detection based on standard 0.35 μm CMOS technology. This lab-on-a-chip microsystem comprises two main units: the actuation unit, and the sensing unit. The chip surface implements a 2D array of microsites, each comprising superficial electrodes and embedded photodiode sensors and logic. The actuation part is based on the DEP technique. The sensing part depends on the fact that particles in the sample can be detected by the changes in optical radiation impinging on the photodiode associated with each micro-site. During the sensing, the actuation voltages are halted, to avoid coupling with the pixel readout. However, due to inertia, the cells keep their position in the liquid.
The disadvantage of these lab-on-a-chip microsystems, can be summarized as follows:
- Based on these two systems, we can detect the position of the levitated cells. However, we cannot sense the actual intensity of the nonuniform electric field that produces the DEP force.
- The measurements here are indirect. In other words, there is no “real-time” detection of the cell response under the effect of the nonuniform electric field, as the actuation part is halted while the sensing part is activated.
- The sensing part in these two microsystems depends on the inertia of the levitated cells. In other words, this sensing approach depends on an external factor, which is the inertia of the levitated cells. Thus, only cells with higher inertia can be sensed and detected by using these two Microsystems.
What is needed is a lab-on-a-chip that can be used for direct measurements, where the variations in the electric field can be sensed and the cell can be characterized while the actuation part is still active.
SUMMARY OF THE INVENTIONThere is therefore provided, according to an aspect of the invention, a sensor device, comprising a source and a drain embedded in a FET; and a gate for the FET, in which the gate is formed of a material whose conductivity is sensitive to an electric, magnetic or electromagnetic field established in a nonconductive medium in contact with the gate. The field may be non-uniform. The FET may comprise two spatially separated gates and two spatially separated drains, with a common source. Two sensor devices may be connected, where wherein the FET of the first sensor device is a p-type FET and the FET of the second sensor device is a n-type FET. The sensor device may be connected in an array of sensor devices.
According to a further aspect of the invention, there is provided a detection apparatus, the detection apparatus comprising a chamber; a port or ports for introducing a sample into the chamber; an actuation unit for establishing a controllable electromagnetic field in the chamber; and a FET sensing unit for sensing changes in the electromagnetic field due to the presence of the sample within the chamber. The FET sensing unit may be comprised of sensor devices described above. The changes in the electromagnetic field sensed by the sensing unit may be used to determine the impedance of the sample, or a characterization unit may use the changes sensed by the sensor unit to make a 2D image of the electromagnetic field. The actuation unit may be responsive to feedback from the sensor device. The actuation unit may comprise an array of electrodes, for example in a quadrupole arrangement, and the sensing unit may comprise an array of sensors interspersed with the array of electrodes. At least one of the electrodes and sensors may receive power from an electromagnetic source, wherein the electromagnetic energy is directed by mirrors controlled by the actuation unit, or from a power source controlled by the actuation unit. The electrodes may be elongate members, the elongate members receiving power at one end and generating the electromagnetic field at the other end in response to the power.
According to a further aspect of the invention, there is provided a method of detecting a sample using dielectrophoresis, using the sensor device and detection apparatus described, where the electromagnetic field is generated and the changes in the electromagnetic field are sensed simultaneously. The particle may be organic matter or a cell.
Other aspects of the invention will be found in the detailed description and claims that follow.
BRIEF DESCRIPTION OF THE DRAWINGSThere will now be given a detailed description of preferred embodiments of the invention, with reference to the drawings, by way of illustration only and not limiting the scope of the invention, in which like numerals refer to like elements, and in which:
The electric field imager disclosed herein is based on conventional TSMC 0.18 μm CMOS technology. Some simulation and experimental results are presented at the end of the disclosure. Referring now to
The Actuation Unit
The actuation unit 12 comprises poles 24, or electrodes, that generate the electric field in the chamber 18. The poles 24 are spatially distributed as shown in
Referring now to
where GQUAD(Z) collects the geometric dependencies and
where ε*p is the complex permittivity of the cell with radius α immersed in a media with complex permittivity ε*m. From the first equation, we can observe that the force Fz is proportional to α5 (radius)5, so we can levitate the small particles using this configuration. On the other hand, the quadrupole levitator comprises an azimuthally symmetric electrode arrangement capable of sustaining passive stable particle levitation. Also, as a diagnostic tool, quadrupole levitation offers researchers insight into the detailed electrical composition of materials. For these reasons, we selected the quadrupole electrode configuration as an actuation part in our design. It will be apparent to those skilled in the art that other designs may also be used.
To implement a large (100 μm) quadrupole system in the 0.18 CMOS technology, we are using four identical octagons using metal2 layer. These octagons are in the x-y plane and arranged symmetrically about the z-axis (see
The Sensing Unit
The sensing unit 14 is composed of an array of the Differential Electric Field Sensitive MOSFET (DeFET) 40 shown in
The Electric Field Sensitive Field Effect Transistor (eFET)
In the DEP levitation process, the manipulating electric field is a nonuniform electric field (i.e. the electric field is a function of the distance). Thus, we can detect the electric field by using the Electric Field Sensitive MOSFET (eFET) 42 shown in
The Differential Electric Field Sensitive MOSFET (DeFET)
Referring to
The Read-out Circuit
For the read-out circuit 50, a higher differential gain is needed to amplify the small current signal at the output; also, it has to have a high common mode rejection ratio (CMRR) to reject any common mode signal. Referring to
The Characterization Unit
The characterization unit 16 reads the output of the sensors 28 and develops a 2D image for the values and compares it with the actuated value. The difference between the actuation values and the sensed values are used to detect and characterize the levitated sample 26 and the characteristics of the contents and liquid inside the micro-channel which may be used as the chamber 18. The characterization unit 16 can also use a sequence of images and process them using image and video processing algorithms to identify the contents of the sample, algorithms such as edge detection, motion tracking, or DSP techniques.
The Controller
The controller 20 adjusts the value of the actuation unit 12 so it generates the required force. The controller 20 may adjust the actuation values using preprogrammed values, or it can read values from the sensing unit 14 or the characterization unit 16 to adjust the actuation unit 12 if needed.
Sensor-Actuation Integration
The integrated quadruple poles 24 with the sensing unit 14 is shown in
- a) The Electric field sensors didn't disturb the profile of the electric field; alternatively, it improves the profile as we under a very small levitation height (Z=3 μm) the levitated particle is on the stable range of operation. In other words, the insertion of the DeFETs reduces the appearance of the unstable regime of operation, thus, we can easily levitate the cells can passively.
- b) The z component of the dielectrophoertic force is increased, so we can levitate the heavy cells without any need of any other external forces, also, we can levitate the cell far from the electrodes, so many processes can be done (e.g. cell fusion, . . . etc. . . . ).
The sensing part (i.e. DeFET) is analyzed, designed, simulated, and implemented using Cadence analog design tool. The schematic representation of a single DeFET 40 is shown in
DeFET as an Impedance Sensor
We can also use a DeFET 40 as an impedance sensor by using the technique shown in
Here we have a biocell 26 above the DeFET 40, so the output voltage (Vowcell) is related to Vin by the equation:
where RF is the feedback resistance, CF is the feedback capacitance, Rsen is the output resistance of the DeFET 40, Rcell is the biocell 26 resistance, and Ccell is the biocell 26 capacitance. To get Rsen, we will determine the output voltage without the biocell 26, and the above equation will be:
From the above equation, we can get Rsen, so we can simply use this value in the first equation to get the impedance of the biocell (i.e. Rcell//Ccell).
Simulation
To verify the operational characteristics of the proposed read out circuit 50, a simulation was developed using PSPICE version 7.1. Then, the proposed CMIA was prototyped and the simulation results were verified. The proposed current-mode instrumentation amplifier (CMIA) is shown in
Immaterial modifications may be made to the invention described here without departing from the invention. In the claims, the word “comprising” preceding a listing of claim elements does not exclude other elements being present in the method or apparatus referred to. In the claims, the use of the indefinite article preceding an element does not exclude more than one of the element being present.
Claims
1. A sensor device, comprising:
- a source and a drain embedded in a FET;
- a gate for the FET, in which the gate is formed of a material whose conductivity is sensitive to an electric or magnetic field established in a nonconductive medium in contact with the gate.
2. The sensor device of claim 1 wherein the electric or magnetic field is a time varying electromagnetic field.
3. The sensor device of claim 1 further comprising an additional gate and an additional drain forming an additional FET, with the source acting as a source for the additional gate and additional drain.
4. The sensor device of claim 3 in which the FET is a p-type FET and the additional FET is an n-type FET.
5. The sensor device of claim 1 connected in an array of sensor devices.
6. The sensor device of claim 1 connected to a detection apparatus, the detection apparatus comprising:
- a chamber;
- a port for introducing a sample into the chamber; and
- an actuation unit for establishing a controllable electromagnetic field in the chamber;
- whereby the sensor device in operation senses changes in the electromagnetic field due to the presence of the sample within the electromagnetic field.
7. The sensor device of claim 4 connected to a detection apparatus, the detection apparatus comprising:
- a chamber;
- a port for introducing a sample into the chamber; and
- an actuation unit for establishing a controllable electromagnetic field in the chamber;
- whereby the sensor device in operation senses changes in the electromagnetic field due to the presence of the sample within the electromagnetic field.
8. The sensor device of claim 7, wherein the changes in the electromagnetic field sensed by the sensor device are used to determine the impedance of the sample.
9. The sensor device of claim 7 wherein a characterization unit uses the changes sensed by the sensor unit to make a 2D image of the electromagnetic field.
10. The sensor device of claim 7 wherein the actuation unit is responsive to feedback from the sensor device.
11-40. (canceled)
Type: Application
Filed: Jun 22, 2007
Publication Date: Oct 18, 2007
Applicant: CETECH SOLUTIONS INC. (Calgary)
Inventors: Yehya Ghallab (Calgary), Wael Badawy (Calgary)
Application Number: 11/767,235
International Classification: H01L 29/82 (20060101); G01R 33/00 (20060101);