Solid state RF oscillator-detector for flow cytometer

Details Solid state RF oscillator-detector for flow cytometer Solid state RF oscillator-detector for flow cytometer

1999-08-13

2001-11-27

Brown, Glenn W. (Department: 2858)

Electricity: measuring and testing

Determining nonelectric properties by measuring electric...

C324S071400, C324S610000, C324S316000

Reexamination Certificate

active

06323632

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates in general to RF oscillator/detectors of the type that are used for conducting electrical measurements of particles (e.g., blood cells) contained in a carrier fluid in a flow cytometer system. The invention is particularly directed to a new and improved solid state RF oscillator-detector circuit, that employs a dual junction field effect transistor (JFET)-based Hartley RF oscillator, having a relatively low Q tank circuit, that is coupled to the flow cell by an impedance-matching transformer.
BACKGROUND OF THE INVENTION
As an adjunct to the diagnosis and treatment of disease, the medical industry commonly employs various types of particle flow cytometers, such as that diagrammatically illustrated at
10
in
FIG. 1
, to analyze particles in a patient's body fluid (e.g., blood cells). For analyzing a patient's blood, for example, a whole blood sample is initially diluted with a saline solution, lysed to explode all the red cells, and then stabilized to return the remaining white cells to their original size.
The prepared blood sample is then placed in a sample holding chamber
12
, and a stream of the blood sample is conveyed along a flow channel
11
from the holding chamber
12
through a restricted orifice or aperture
14
, that allows particles to be counted one at the time, and into a receiving chamber
16
. Via electrodes
21
and
23
that are respectively coupled to either end of the flow cell's holding chambers (holding chamber
12
and receiving chamber
16
) a DC electrical field for measuring the displaced volume of each particle and an RF field for measuring the density of each particle passing through the aperture
14
are applied to the flow cell
10
by way of an oscillator-detector circuit
17
, which is preferably configured as a Hartley oscillator (although other oscillator architectures may also be used).
As particles pass through the flow cell orifice
14
, they introduce changes in the resistance of the orifice in proportion to their size or volume. These changes in resistance are reflected as DC voltage pulses at the electrodes
21
and
23
. The density or opacity of the blood cells is associated with changes in reactance of the flow cell aperture
14
. By coupling the electrodes
21
and
23
of the flow cell
10
in parallel with the resonance (LC tank) circuit of the RF oscillator-detector circuit
17
, changes in the reactance of the flow cell are reflected as a corresponding change in the operation of the RF oscillator, which is measured by means of an RF pulse detector/demodulator.
For non-limiting examples of U.S. Patent literature detailing conventional electronic tube based flow cell RF oscillator detector circuits, attention may be directed to the 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. No. 4,525,666; and Coulter et al, U.S. Pat. No. 4,791,355.
Now although a tube-based flow cell measurement circuit of the type shown in
FIG. 1
is effective to provide an indication of both particle size and density, it suffers from a number of problems which are both costly and time-consuming to remedy. A fundamental shortcoming is the fact that it was originally designed as and continues to be configured using relatively old electronic tube components. This potentially impacts component 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 RF (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 transconductance 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 flow cell.
SUMMARY OF THE INVENTION
While it might seem that a straightforward solution to the tube aging problem would simply involve replacing the electronic tube (e.g., triode) with a solid state device, such as a bipolar transistor, MOSFET, JFET and the like, such is not the case. Investigation by the present inventors has revealed that, in order to exhibit the sensitivity necessary to successfully function as a detector, the tube must operate over a relatively narrow, steep sloped region of its plate current versus plate voltage relationship, shown at
27
in the triode characteristic of FIG.
2
.
It has been found that the relatively short mean time before failure (MTBF) of a conventional electronic tube-based flow cell measurement circuit is due to the fact that, as the tube ages, the slope of its plate current versus plate voltage characteristic at V
GRID
=0 falls off quickly, and thereby degrades the tube's sensitivity to the extent that it no longer effectively functions as a detector, even though it may continue to operate as an RF oscillator.
If one considers the active device's (tube or JFET) operating range sensitivity (plate or drain voltage vs. grid or gate voltage) as a measure of transconductance (gm) dependence, from a comparison of the respective characteristic curve sets shown in
FIGS. 5A
(triode) and
5
B (JFETs), it can be readily seen that a JFET provides a considerable improvement over a tube.
Typically, for a triode, this becomes 300 v/0.1 v=3000:1 vs. for a JFET 20 v/0.1 v=200:1. This is very important, given the small change in grid/gate voltage for a disturbance caused by the blood cell in the flow cell. Thus, an electronic tube will see a times fifteen degradation over a JFET for the same grid/gate voltage change, which makes the tube very dependent upon it's transconductance gm. A small decay in the tube's gm will then result in complete loss of detection capability. Thus, simply reconfiguring a conventional tube-based Hartley oscillator out of solid state components will not necessarily solve the problem.
In accordance with the present invention, the discovery of the above-discussed sensitivity-dependent slope limitation requirement has led the present inventors to design a new and improved solid state-based Hartley oscillator-configured flow cell detection circuit, that not only solves the tube-aging problem, but provides substantially improved performance. As will be described, the oscillator-detection circuit of the invention employs a pair of JFETs as its principal active devices (respectively operating in Class C and Class AB mode), which enables the circuit to achieve near zero noise operation with a very high V
DS
vs. I
DS
slope at a V
GS
=0 volts.
Advantageously, JFETs are inherently noiseless, except for the thermal noise intrinsic with channel resistance between the drain and the source. In the operation of the oscillator/detector, it is very easy to be misled as to the value of rms noise level seen at the detector output. The circuit noise that is coupled to the detector output is primarily related to the conduction time of JFET channel resistance. The shorter conduction time, reduction of channel resistance, or reduction of channel current, the lower the effective noise.
As will be described, operation with two JFETs in different class modes helps reduce the noise floor. A low current in the Class AB JFET stage in combination with low channel resistance allow for a lower noise floor. When the Class C JFET stage switches on, then only for that time is the additional channel device a noise source. The tradeoff is conduction time vs. the product of conduction current and conduction resistance.
In accordance with a preferred embodiment of the invention, a pair of parallel-coupled JFETs having different transfer functions, in particular different pinchoff V
GS
and max I
DSS
characteristics, are employed as the principal active element of the RF oscillator. As pointed out briefly above, there are two modes of operation that occ

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