Electricity: measuring and testing – Determining nonelectric properties by measuring electric... – Particle counting
Reexamination Certificate
1999-05-26
2001-07-10
Brown, Glenn W. (Department: 2858)
Electricity: measuring and testing
Determining nonelectric properties by measuring electric...
Particle counting
C324S439000, C324S446000, C377S012000
Reexamination Certificate
active
06259242
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is related to application U.S. patent application Ser. No. 08/887,588, filed Jul. 3, 1997 and entitled “Method and Apparatus for Sensing and Characterizing Particles” (now issued as U.S. Pat. No. 6,111,398). This application is also related to a Continuation-In-Part of said application, filed Jul. 1, 1998 as U.S. patent application Ser. No. 09/108,997 and entitled “Potential-Sensing Method and Apparatus for Sensing and Characterizing Particles by the Coulter Principle”. Both related applications are incorporated herein by reference, being assigned in common with this application to the same assignee.
CROSS-REFERENCE TO RELATED PATENTS
Reference is made to the following U.S. patents, each owned by the assignee of the present invention: U.S. Pat. Nos. 2,656,508; 2,869,078; 2,985,830; 3,259,842; 3,502,974; 3,771,058; 3,810,010; 3,902,115; 3,949,198; and 4,797,624. The disclosures of these patents provide exemplary prior art of interest regarding the invention hereinafter described, each of said patents being incorporated herein by reference.
Reference is also made to U.S. Pat. No. 4,161,690. The disclosure of this patent provides a further example of the prior art related to the invention hereinafter described and is incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to improvements in methods and apparatus for sensing and characterizing small particles, such as blood cells or metallic powders, suspended in a liquid medium having electrical impedance per unit volume which differs from that of the particles. More particularly, one aspect of the invention relates to improvements in methods and apparatus for sensing and characterizing such particles, whereby increased sensitivity to particle characteristics other than physical volume is provided. A second aspect of the invention relates to improvements in the non-volumetric sensitivity of methods and apparatus for sensing and characterizing such particles by apparatus operating according to the Coulter principle.
2. Discussion of the Prior Art:
U.S. Pat. No. 2,656,508 to Wallace H. Coulter (the '508 patent) discloses a seminal method for sensing particles suspended in a liquid medium. An exemplary apparatus for implementing such method is schematically illustrated in FIG.
1
. Such apparatus comprises a dual-compartment dielectric vessel
6
, which defines first and second compartments
6
A and
6
B separated by a dielectric wall
7
. Each of the compartments
6
A and
6
B is adapted to contain, and is filled with, a liquid medium M. Wall
7
is provided with a relatively large opening
7
A, which is sealed by a thin wafer W made of a homogeneous dielectric material. A small through-hole formed in wafer W provides a conduit
10
, which constitutes the only operative connection between compartments
6
A and
6
B. The particles to be sensed and characterized are suspended at an appropriate concentration in liquid medium M and introduced into compartment
6
A through a suitable inlet port
8
(or
9
) formed therein. A vacuum, provided by an appropriate source in liquid-handling system
13
and operatively coupled to an outlet port
11
suitably formed in compartment
6
B, causes the particle suspension to flow from compartment
6
A into compartment
6
B through conduit
10
, discussed in detail below. Each particle in the suspension displaces its own volume of liquid medium M, and conduit
10
provides a consistent reference volume against which that displaced volume may be compared. If the dimensions of conduit
10
and the concentration of particles in the suspension are appropriately selected, particles can be made to transit conduit
10
more or less individually. Conduit
10
then functions as a miniature volumeter, capable under suitable conditions of making sensible the liquid displaced by individual microscopic particles.
To enable convenient sensing of the liquid displacement occasioned by particles transiting conduit
10
, liquid medium M is made to have electrical impedance per unit volume which differs from that of the particles. Both aqueous and non-aqueous liquid solutions of a variety of electrolytes have been used as medium M to suspend and carry the particles being characterized through conduit
10
. The electrical resistivity p of such liquid media is usually in the approximate range between 30 ohm·cm and 200 ohm·cm; e.g., at room temperature the resistivity of a commercial isotonic saline solution (Isoton II, Coulter Corporation) is approximately 61.4 ohm·cm. The contrast in electrical impedance between particle and medium M thus converts the volume of displaced liquid into a proportional change in the electrical impedance of the liquid column in conduit
10
.
The remainder of the apparatus in
FIG. 1
forms a two-electrode measurement system responsive to such changes in electrical impedance. Excitation electrodes
15
and
16
are positioned in respective compartments
6
A and
6
B and operatively connected to a source
17
of electrical current, whereby a nominal electrical current is caused to flow through conduit
10
simultaneously with the particle suspension. Sensing circuitry
18
, also operatively connected to excitation electrodes
15
and
16
, operates to sense and process pulsations in current between these electrodes. Thus, as individual particles pass through conduit
10
, sensing circuit
19
produces an electrical signal pulse having an amplitude which is proportional to the impedance change and therefore characteristic of the particle volume. Additional circuits
20
process the particle signal pulses to provide a count of particles exceeding some particular volumetric threshold. If current source
17
is caused to provide a constant current (so that pulse amplitudes are made insensitive to temperature-induced changes in the electrical conductivity of suspending medium M), the volumetric distribution of the particles may be conveniently characterized through use of multiple-threshold circuitry
21
as described in U.S. Pat. No. 3,259,842 to Wallace H. Coulter et al. Further, if current source
17
is caused to provide at least one alternating-current component at high frequency as discussed in U.S. Pat. No. 3,502,974 to Wallace H. Coulter and W. R. Hogg, an apparent volume reflecting the internal conductivity of biological cells may be similarly characterized. If liquid-handling system
13
comprises a positive-displacement metering system, e.g., such as disclosed in U.S. Pat. No. 2,869,078 to Wallace H. Coulter and Joseph R. Coulter, Jr., such particle counts may be readily displayed or recorded in terms of particle concentration by appropriate devices
22
. This method of sensing and characterizing particles, by suspending them in a liquid medium having electrical impedance per unit volume which differs from that of the particles and passing the resulting particle suspension through a constricting conduit while monitoring the electrical current flow through the conduit, has become known as the Coulter principle.
A substantial interphase layer of anions or cations may result when metallic conductors are immersed in a liquid medium comprising ionic species and the ionic medium is constrained to maintain a potential gradient in the vicinity of the conductive material. The predominant ionic type surrounding such conductors depends on the polarity of the potential gradient at the material surface, i.e., on whether electrons enter or leave the material. As noted in the '508 patent, excitation electrodes
15
and
16
develop such concentration polarization layers at their surfaces. At a given temperature, properties of said polarization layers depend on the material of each electrode, the electrolyte, and the local rate of electron exchange (i.e., the current density) through the polarization layer. In the electrode art it is known to minimize local gradients in current density, whereby polarization layers are substantially uniform in thickness and vary from approximat
Dunstan Harvey J.
Graham Marshall D.
Alter Mitchell E.
Brown Glenn W.
Coulter International Corp.
Kurz Warren W.
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