Method And Apparatus For Characterizing And Counting Particles, In Particular, Biological Particles
First Claim
1. Method for the detection of the presence of particles (BEADS) possibly present in points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL) comprising the steps of:
- i. deactivating the force field (F);
ii. measuring, in at least a time interval following to the deactivation and selected as a function of the dynamic of the settling and/or Brownian movements to which the particles with a deactivated field are subjected, the grey level generated by first sensors (PIXEL_IJ) associated with said stable equilibrium points (PEQ) and by second sensors (PIXEL_REF) associated with space regions which can not certainty be occupied by particles because of the current configuration of said force field (F);
iii. reactivating the force field (F);
iv. repeating the steps from i) to iii) a number of times, substantially comparable with the convergence rate to its asymptotic value, of the variance of the values of the grey level measured on said second sensors, assumed as a reference (PIXEL_REF);
v. classifying a point of equilibrium as occupied by particles if, in the considered temporal series of measurements, the standard deviation of the grey level values detected on the first sensors, associated with such point of equilibrium (PEQ), results higher than a pre-fixed threshold (THR).
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Abstract
The present invention relates to a method and an apparatus for the characterization and/or the counting of particles by means of non uniform, time variable force fields and integrated optical or impedance meter sensors. The force fields can be of positive or negative dielectrophoresis, electrophoresis or electro-hydrodynamic motions, characterized by a set of stable equilibrium points for the particles (solid, liquid or gaseous); the same method is suitable for the manipulation of droplets (liquid particles) by exploiting effects known to the international scientific community with the name of Electro-wetting on dielectric. The aim of the present invention is to act on the control of the position of each particle which is present in the sample, for the purpose of displacing such particles in a deterministic or statistical way, in order to detect their presence with the integrated optical or impedance meter sensors and/or characterize their type, for the purpose of counting or manipulating them in an efficient way.
104 Citations
26 Claims
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1. Method for the detection of the presence of particles (BEADS) possibly present in points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL) comprising the steps of:
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i. deactivating the force field (F); ii. measuring, in at least a time interval following to the deactivation and selected as a function of the dynamic of the settling and/or Brownian movements to which the particles with a deactivated field are subjected, the grey level generated by first sensors (PIXEL_IJ) associated with said stable equilibrium points (PEQ) and by second sensors (PIXEL_REF) associated with space regions which can not certainty be occupied by particles because of the current configuration of said force field (F); iii. reactivating the force field (F); iv. repeating the steps from i) to iii) a number of times, substantially comparable with the convergence rate to its asymptotic value, of the variance of the values of the grey level measured on said second sensors, assumed as a reference (PIXEL_REF); v. classifying a point of equilibrium as occupied by particles if, in the considered temporal series of measurements, the standard deviation of the grey level values detected on the first sensors, associated with such point of equilibrium (PEQ), results higher than a pre-fixed threshold (THR). - View Dependent Claims (2, 8, 15, 16, 17, 18, 19)
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3. Method for the detection of the presence of particles (BEADS) possibly existing in points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL), comprising the steps of:
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i. measuring the grey level generated by first sensors (PIXEL_STA) associated with said points of stable equilibrium (PEQ), and by reference sensors (PIXEL_REF) associated with space regions which certainly can not be occupied by particles in a first current configuration of said force field (F); ii) modifying said force field (F) in order to impart it a second current configuration wherein said stable equilibrium points are displaced in correspondence with second sensors (PIXEL_TGT), different from the first sensors; iii) measuring the grey level generated by the second sensors (PIXEL_TGT) and by reference sensors (PIXEL_REF) associated with space regions which can not certainly be occupied by particles in said second current configuration of said force field (F); iv) determining the difference (DIFF_IMG) between the grey level values detected to the preceding points i) and iii); v) repeating the steps i) to iv); vi) processing differential grey level values in order to classify the points of stable equilibrium (PEQ) occupied by particles and those not occupied. - View Dependent Claims (4)
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5. Method for the detection of the presence of particles (BEADS) possibly existing in points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL), comprising the steps of:
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i. modifying said force field (F) so as to displace said points of stable equilibrium (PEQ) to get said particles (BEADS) pass in correspondence with respective sensors (PIXEL_IJ); ii. measuring the grey level generated by sensors (PIXEL_IJ) associated with the passage of said different points of stable equilibrium (PEQ), with a frequency substantially higher than the settling time of said particles in the new equilibrium position; iii. classifying the presence or the absence of particles through the measurement of at least a characteristic parameter of the temporal evolution of the grey level measured by said sensors (PIXEL_IJ). - View Dependent Claims (6, 7)
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9. Method for the characterization of particles (BEADS) existing in points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL), comprising the steps of:
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i. modifying said force field (F) so as to displace said points of stable equilibrium (PEQ) by passing said particles (BEADS) in correspondence with respective sensors (PIXEL_IJ); ii. measuring the grey level generated by sensors (PIXEL IJ) associated with the passage of the different points of stable equilibrium (PEQ) containing particles, with a frequency substantially higher than the settling time of said particles in the new position of equilibrium; iii. processing characteristic parameters of the temporal evolution of the grey level measurement in order to estimate the nature of said particles. - View Dependent Claims (10)
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11. Method for counting the number of particles (BEADS) of a multiplicity of types (NTP), existing in points of stable equilibrium (PEQ) of a force field (F) acting on said particles and generated by an array of electrodes (EL), through the execution of the following steps:
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i. modifying the force field (F) so as to displace said points of stable equilibrium (PEQ) by passing said particles (BEADS) in correspondence with respective sensors (PIXEL_IJ); ii. measuring the grey level detectable by the sensors (PIXEL_IJ) associated with the passage of the different points of stable equilibrium (PEQ) containing particles, with a frequency substantially higher than the settling time of the particles in the new position of equilibrium; iii. processing characteristic parameters of the temporal evolution of the grey level measurement associated with each point of stable equilibrium (PEQ) for detecting if the associated cage is empty, if it contains a particle of a type or if it contains more particles; iv. determining in a numerical way the combination of countings of particles of each type (NCELLSt) which better approximates to the measured value of cages with a single particle of each type (Pt_1_MEAS) and empty cages (EC_MEAS). - View Dependent Claims (12, 13, 14)
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20. Apparatus for the detection and/or characterization of particles (BEADS) comprising:
- means for the generation of points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL); and
optical sensors (PIXELS) associated with said electrodes;
characterized in that said optical sensors are made so as to detect the incident optical power on a sensor portion substantially lower than the dimensions of the particles. - View Dependent Claims (21, 23, 24, 25, 26)
- means for the generation of points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL); and
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22. Apparatus for the detection and/or characterization of particles (BEADS) comprising means for the generation of points of stable equilibrium (PEQ) of a force field (F) acting on said particles, generated by an array of electrodes (EL);
- and sensors (PIXEL) associated with said electrodes, characterized in that to each electrode (EL) a first sensor (PIXEL_V) for detecting the transit of said particles in a vertical direction, and a second sensor (PIXEL_H) for detecting the transit of said particles in a horizontal direction are associated.
Specification