DC/RF blood cell detector using isolated bridge circuit...

Electricity: measuring and testing – A material property using electrostatic phenomenon – In a liquid

Reexamination Certificate

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C324S071100, C422S082020

Reexamination Certificate

active

06204668

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates in general to detectors of the type used for conducting electrical measurements of parameters of objects, such as but not limited to the detection of particles (e.g., blood cells) contained in a carrier fluid supplied to a hematology analyzer. The invention is particularly directed to a new and improved DC/RF bridge-configured object parameter detector having an automatic amplitude and phase balance circuit that models the behavior of the object, particularly an object having non-linear characteristics, and compensates for (non-linear) variations in conditions other than the parameter being measured.
BACKGROUND OF THE INVENTION
As an adjunct to the diagnosis and treatment of disease, the medical industry commonly employs various types of particle flow systems, such as that diagrammatically illustrated in
FIG. 1
, to analyze particles or cells in a patient's body fluid (e.g., blood cells). To this end, a carrier fluid (e.g., saline) stream
1
, containing particles/cells
2
of a centrifuged blood sample stored in a blood sample holding chamber
3
, is directed along a flow channel
4
through a restricted flowcell ‘measurement’ aperture
5
of a flowcell
6
into a receiving chamber
7
. The flowcell measurement aperture
5
is sized and configured to allow the particles to be counted one at the time as they pass through the flowcell, and includes a pair of electrodes
8
and
9
, to which a DC electrical field for measuring the size or volume of each particle and an RF field for measuring the density of each particle passing through the flowcell aperture
5
are applied.
In particular, the dimensions of the flowcell measurement aperture
5
define a “steady state” flowcell characteristic impedance R
a
, which may be represented by a single capacitance and resistance value at the frequency of interest. As particles pass through the flowcell measurement aperture
5
, they introduce changes in the resistance of the flowcell in proportion to their size or volume. These changes in aperture resistance are reflected as DC voltage pulses at the electrodes
8
and
9
, and can be measured directly.
In addition, the density or opacity of a blood cell or particle is reflected as a change in the reactance of the flowcell aperture, and has been conventionally measured by coupling the electrodes
8
and
9
in parallel with the resonance (LC tank) circuit of an associated RF oscillator-detector circuit
10
. This change in reactance of the flowcell causes a corresponding change in the operation of the RF oscillator, which can be measured by means of an RF pulse detector/demodulator. For an illustration of non-limiting examples of U.S. patent literature detailing such conventional oscillator-based flowcell RF detector circuits attention may be directed to the U.S. patents to Coulter et al, U.S. Pat. No. 3,502,974; Groves et al, U.S. Pat. No. 4,298,836; Groves et al, U.S. Pat. No. 4,525,666; and Coulter et al, U.S. Pat. No. 4,791,355.
Now although an RF oscillator-based flowcell measurement circuit of the type generally shown in
FIG. 1
is effective to provide an indication of both size and density of each blood cell, it suffers from a number of problems which are both costly and time-consuming to remedy. One fundamental shortcoming is the fact that the particle detection mechanism was originally designed as and continues to be configured as a tube-based RF Hartley oscillator circuit. This potentially impacts circuit availability, as the number of manufacturers of vacuum (as well as gas filled) electronic tubes continues to decline.
In addition, the effective lifetime of a newly purchased and installed tube in the Hartley oscillator is not only unpredictable, but experience has shown that the effective functionality of most tubes within the Hartley oscillator—detector circuit is very limited, (even though a tube tester measurement shows a tube to be good). At best a tube can expect to last somewhere in a range of three to nine months—and typically involves on the order of two repair/maintenance service calls per year per flowcell.
SUMMARY OF THE INVENTION
In accordance with the present invention, rather than use a change-in-reactance based, RF Hartley oscillator-configured detector to measure particle/cell density, both cell volume and internal cellular conductivity are measured by a DC/RF-stimulated bridge detector. The bridge detector of the invention has a circuit configuration generally of the type employed in a Wheatstone bridge, and uses opto-isolator components for galvanic isolation from sources of signal degradation that might otherwise substantially impair the ability of the bridge to conduct accurate particle detection measurements.
Like a conventional Wheatstone bridge, the DC/RF-driven bridge of the invention includes a first voltage divider branch, in which the object being monitored (e.g., a flowcell) is installed. The first branch of the bridge also includes a linear impedance element connected in a series circuit path between bridge stimulation terminals, across which a high frequency voltage (on the order of several tens of MHz), and a DC excitation voltage are applied. Also coupled in circuit with the flowcell and one of the stimulation terminals is an automatic amplitude and phase balancing, non-linear network (such as a resistor-capacitor network).
The DC/RF stimulated bridge detector of the invention also has a second voltage divider branch containing a flowcell circuit model, which mirrors the impedance of the actual flowcell, and another linear impedance element connected in a series circuit path between the bridge stimulation terminals. The flowcell circuit model functions as an automatic amplitude and phase balance circuit, and comprises an adjustable non-linear network, such as, but not limited to a variable capacitor and a linear resistor coupled in circuit between the high frequency voltage terminal and a bridge output node. The linear resistance elements of the DC/RF bridge of the invention virtually eliminate second order Laplacian effects associated with coupling amplifier circuits. The input capacitance of each coupling amplifier circuit—together with the linear resistor—forms a first order filter having a cut-off frequency defined by the values of the resistor and the input capacitance of an associated coupling amplifier.
A first bridge output node is coupled to a first current gain amplifier, whose output is coupled to a difference amplifier. The difference amplifier is also coupled to the output of a second current gain amplifier, the input of which is coupled to a second bridge output node. This differential amplifier connection effectively cancels inherent common-mode noise, as well as residual noise caused by the imbalance in the two branches of the bridge. The output of the difference amplifier is coupled to a DC/RF discriminator and associated downstream processing circuitry.
By virtue of opto-isolator coupling and its isolated self-powered architecture, the modified Wheatstone bridge detector of the invention is effectively a “floating” bridge, that galvanically isolates the front-end signal detection circuits from very high frequency noise components sourced from the RF oscillator. As a result, filter bandwidths in the downstream signal processing circuits can be made much wider to accommodate all of the signal energy density, with virtually no interference from RF noise in the detected signal path.
A fundamental drawback of a standard Wheatstone bridge network is the degradation of signal quality, and a complete loss of signal in cases involving very high frequency detection schemes, such as RF pulse detection in a flowcell. This signal degradation is mainly due to resistances and reactances parasitic in the interconnect components. For a properly functioning RF pre-amplifier, the parasitics inherent in the bridge must be virtually eliminated. This is effectively accomplished in the invention by using commercially available high noise rejection components, that allow parasitic-minimizing,

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