U.S. patent application number 11/597156 was filed with the patent office on 2012-02-09 for magnetic particle resuspension probe module.
Invention is credited to Martin Fletcher, Ann Jacob, Martin Trump.
Application Number | 20120034132 11/597156 |
Document ID | / |
Family ID | 35451502 |
Filed Date | 2012-02-09 |
United States Patent
Application |
20120034132 |
Kind Code |
A1 |
Trump; Martin ; et
al. |
February 9, 2012 |
Magnetic Particle Resuspension Probe Module
Abstract
An acid injection module (100) comprising a dual probe nozzles
(102).
Inventors: |
Trump; Martin; (Pforzheim,
DE) ; Fletcher; Martin; (Winchester, MA) ;
Jacob; Ann; (Stormville, NY) |
Family ID: |
35451502 |
Appl. No.: |
11/597156 |
Filed: |
May 24, 2005 |
PCT Filed: |
May 24, 2005 |
PCT NO: |
PCT/US05/18238 |
371 Date: |
November 15, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60574000 |
May 24, 2004 |
|
|
|
Current U.S.
Class: |
422/32 |
Current CPC
Class: |
B01L 2200/143 20130101;
B01L 9/06 20130101; B01L 2200/025 20130101; G01N 2035/0429
20130101; G01N 2035/0493 20130101; Y10T 436/11 20150115; G01N
35/026 20130101 |
Class at
Publication: |
422/32 |
International
Class: |
B01L 3/02 20060101
B01L003/02 |
Claims
1. A resuspension nozzle module for enabling resuspension of
accumulated particles in a reaction vessel comprising: a probe
housing mountable in an analytical instrument; a mounting recess on
a rear surface of the probe housing for interfacing the module to a
source of resuspension liquid; plural channels, defined within the
probe housing, in fluid communication with the mounting recess;
plural probes, defined within the probe housing, each in fluid
communication with a respective one of the channels; and plural
probe nozzles, formed on a front surface of the probe housing, each
in fluid communication with a respective one of the probes, wherein
the plural probes and probe nozzles are mutually parallel.
2. The resuspension nozzle module of claim 1 wherein the plural
probe nozzles are configured to dispense parallel streams of
resuspension liquid.
3. In an automated analysis system having at least one resuspension
liquid nozzle and serially conveyed reaction vessels in which
solids particles are accumulated against an interior wall of each
reaction vessel and require resuspension, a method of verifying
each nozzle can project a stream of resuspension liquid within a
target field on the interior wall of each reaction vessel relative
to the accumulated solids particles, the method comprising the
steps of: defining linear and angular dimensional offset values
between the nozzle and the target field necessary for the
resuspension liquid stream to hit the target field; for all system
components having non-zero positional tolerances in a respective
dimension or dimensions, identifying the respective positional
tolerance; determining the nominal value and tolerance for the
difference in the respective dimension or dimensions between the
nozzle and the respective target as a closure value; calculating
the total deviation of the closure value in the respective
dimension or dimensions for all components having a non-zero
positional tolerance in the respective dimension; for all system
components having an asymmetric tolerance distribution in the
respective dimension or dimensions, determining the mean values and
deviation for each; for all system components having a folded
normal tolerance distribution in the respective dimension or
dimensions, determining the mean values and deviations for each;
determining the statistical closure value with tolerance based upon
the determined mean values and deviations and the calculated total
deviation in the respective dimension or dimensions; from the total
deviation of the closure value in each dimension or dimensions,
calculating the arithmetic deviation of the target; from the
statistical closure values in each dimension, estimating the total
statistical deviation from the target; and from the total
statistical deviation, deriving the statistical error from the
target with tolerance.
4. In an automated analysis system having at least one resuspension
liquid nozzle and serially conveyed reaction vessels in which solid
particles are accumulated against an interior wall of each reaction
vessel, the solid particles requiring selective resuspension, a
method of verifying each nozzle can project a stream of
resuspension liquid within a target field on the interior wall of
each reaction vessel relative to the accumulated solid particles,
the method comprising the steps of: defining ideal linear and
angular offset values for the nozzle, relative to the cuvette,
along vertical and horizontal linear dimensions and in the angular
plane defined thereby, the ideal linear and angular offset values
enabling resuspension liquid to impact the cuvette within the
target field; identifying all structural components contributing to
tolerance stack-up in each linear dimension and angular plane;
identifying the nominal linear dimension or angular orientation and
the tolerance range, if any, for each structural component in each
linear dimension and angular plane, respectively; arithmetically
calculating a nominal closure value for each linear dimension and
angular plane as the difference between the ideal linear and
angular offset values and the respective summed structural
component nominal linear and angular measurements; determining the
tolerance range for the nominal closure value for each linear
dimension and angular plane as the arithmetic sum of the respective
tolerances of the structural components in the respective linear
dimension and angular plane; determining tolerance mean and
deviation values for each structural component in each linear
dimension and angular plane; statistically calculating the nominal
closure value for each linear dimension and angular plane as a
distributed average of the tolerance mean values of the respective
structural components; statistically calculating the respective
tolerance zone for each linear dimension and angular plane from the
tolerance deviation values of the respective structural components;
and orienting the nozzle in the linear dimensions and the angular
plane according to the respective statistically calculated nominal
closure values and tolerance zones.
5. The method of claim 4, wherein the step of orienting comprises
compensating for a cuvette sidewall draft.
6. The method of claim 4, wherein the solid particles are
accumulated against an interior wall of each reaction vessel by
action of a magnet array, and wherein the step of orienting
includes orienting according to statistically calculated nominal
horizontal closure values and tolerance values associated with the
magnet array.
7. The method of claim 4, wherein the step of orienting comprises
compensating for the effect of gravity on a stream of resuspension
liquid.
8. The method of claim 7, wherein the step of compensating for the
effect of gravity comprises further identifying the rate at which
the resuspension liquid flows and the diameter of each nozzle.
9. The resuspension nozzle module of claim 1, further comprising a
buffer zone defined within the housing intermediate the mounting
recess and the plural channels, the buffer zone enabling pressure
equalization between the plural channels.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Prov. Appl. No.
60/574,000, filed May 24, 2004, the entirety of which is hereby
incorporated by reference.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] N/A
BACKGROUND OF THE INVENTION
[0003] Heterogeneous immunoassays typically require the separation
of sought-for components bound to component-selective particles
from unbound or free components of the assay. To increase the
efficiency of this separation, many assays wash the solid phase
(the bound component) of the assay after the initial separation
(the removal or aspiration of the liquid phase). Some
chemiluminescent immunoassays use magnetic separation to remove the
unbound assay components from the reaction vessel prior to addition
of a reagent used in producing chemiluminescence or the detectable
signal indicative of the amount of bound component present. This is
accomplished by using magnetizable particles including, but not
restricted to, paramagnetic particles, superparamagnetic particles,
ferromagnetic particles and ferrimagnetic particles. Tested-for
assay components are bound to component-specific sites on
magnetizable particles during the course of the assay. The
associated magnetizable particles are attracted to magnets for
retention in the reaction vessel while the liquid phase, containing
unbound components, is aspirated from the reaction vessel.
[0004] Washing of the solid phase after the initial separation is
accomplished by dispensing and then aspirating a wash solution,
such as de-ionized water or a wash buffer, while the magnetizable
particles are attracted to the magnet.
[0005] Greater efficiency in washing may be accomplished by moving
the reaction vessels along a magnet array having a gap in the array
structure proximate a wash position, allowing the magnetizable
particles to be resuspended during the dispense of the wash
solution. This is known as resuspension wash. Subsequent positions
in the array include additional magnets, allowing the magnetizable
particles to recollect on the side of the respective vessel.
[0006] Once the contents of the reaction vessel have again
accumulated in a pellet on the side of the reaction vessel and the
wash liquid has been aspirated, it is desirable to resuspend the
particles in an acid reagent used to condition the bound component
reagent. In the prior art, a single stream of acidic reagent is
injected at the pellet. Because the size of the pellet and
limitations on the volume and flow rate of reagent, insufficient
resuspension may result. To address this inadequacy, prior art
systems have resorted to the use of an additional resuspension
magnet disposed on an opposite side of the process path from the
previous separation magnets. The resuspension magnet is configured
to assist in drawing paramagnetic particles into suspension, though
the magnetic field is insufficient to cause an aggregation of
particles on the opposite side of the vessel from where the pellet
had been formed. In addition, since the prior art approach utilizes
a resuspension magnet, there is less motivation to accurately aim
the acid resuspension liquid. Any inhomogeneity in the suspended
particles is addressed by the resuspension magnet.
[0007] It would be preferable to provide a system in which the use
of a resuspension magnet is obviated.
BRIEF SUMMARY OF THE INVENTION
[0008] An improved acid injection module includes dual, parallel
injection probes. A high-precision aiming strategy is employed to
ensure that complete, homogenous resuspension of accumulated
solid-phase particles is achieved, obviating the need for
subsequent resuspension magnet positions.
[0009] The dual, parallel injector probe nozzles are spaced by a
degree necessary to provide substantially adjacent impact zones on
the reaction vessel wall, also referred to as "hit zones" or "hit
points." Through careful control over lateral spacing of the two
nozzles, and thus the two hit zones, and by performing an exacting
analysis of the various physical tolerances which can effect hit
zone location relative to the solid-phase pellet, thorough
resuspension can be achieved without use of a resuspension
magnet.
[0010] Other features, aspects and advantages of the
above-described method and system will be apparent from the
detailed description of the invention that follows.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0011] The invention will be more fully understood by reference to
the following detailed description of the invention in conjunction
with the drawings of which:
[0012] FIG. 1 illustrates an optimal orientation of resuspension
probes relative to a reaction vessel according to the presently
disclosed invention;
[0013] FIG. 2 illustrates certain physical parameters employed in
defining the optimal orientation of the probes of FIG. 1;
[0014] FIG. 3 illustrates additional physical parameters employed
in defining the optimal orientation of the probes of FIG. 1;
[0015] FIG. 4 illustrates additional physical parameters employed
in defining the optimal orientation of the probes of FIG. 1;
[0016] FIG. 5 illustrates additional physical parameters employed
in defining the optimal orientation of the probes of FIG. 1;
[0017] FIG. 6 pictorially illustrates system components which
contribute vertical tolerances and which must be accommodated in
defining the optimal probe orientation of FIG. 1;
[0018] FIG. 7 is a vector diagram representation of the tolerance
contributors of FIG. 6;
[0019] FIG. 8 pictorially illustrates system components which
contribute horizontal tolerances and which must be accommodated in
defining the optimal probe orientation of FIG. 1;
[0020] FIG. 9 is a vector diagram representation of the tolerance
contributors of FIG. 8
[0021] FIG. 10 is a perspective view of a probe module according to
the presently disclosed invention;
[0022] FIG. 11 is a front view of the probe module of FIG. 10;
[0023] FIG. 12 is a section view of the probe module of FIGS. 10
and 11 taken along lines A-A; and
[0024] FIG. 13 is a section view of the probe module of FIGS. 10
and 11 taken along lines B-B.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The presently disclosed concept finds particular
applicability to automated laboratory analytical analyzers in which
paramagnetic particles are drawn into a pellet on the side of a
reaction vessel as part of a separation and wash process. In
particular, in an analyzer in which chemiluminescence is utilized
for determining analyte concentration, the accumulated particles
must be thoroughly resuspended to obtain an accurate reading. One
approach in such systems is to resuspend the accumulated, washed
particles in acid prior to introducing a base, and thus triggering
the chemiluminescent response, at an optical measuring device such
as a luminometer. However, it is noted that the presently disclosed
concept is also applicable to any environment in which thorough
resuspension of accumulated particles is required.
[0026] FIG. 1 illustrates a reaction vessel (also referred to as a
cuvette), a probe nozzle, and the ideal orientation of the probe
with respect to the cuvette. Note that two probes are employed,
though only one is visible in the profile illustrated of FIG. 1.
Linear distance values are given in millimeters. As shown, the
ideal distance below the cuvette top plane where the liquid stream
hits the cuvette wall, referred to as the hit point, is 25.98 mm.
In the illustrated embodiment, this hit point is 5.74 mm above the
centerline of a magnet array which forms the solids pellet and
represents an empirically determined ideal locus of the hit point
for achieving thorough particle resuspension. The probe is angled
6.9 degrees from vertical, with the probe tip being located 0.92
millimeters behind the cuvette centerline and 2.304 mm above the
cuvette top plane. These values are obtained, as described below,
by calculating the worst-case tolerance errors which could effect
the hit point and by finding the locus where, even assuming all
tolerances have a maximum deviation, the hit point will still be
above the magnet centerline.
[0027] One practical aspect not accounted for in the configuration
described in FIG. 1 is the effect of gravity on the liquid stream
itself. The ideal hit point illustrated in FIG. 1 is calculated by
extending the axis of the probe towards the cuvette wall. Because
of the effect of gravity, the actual hit point is slightly below
the one illustrated in FIG. 1. That distance is calculated in the
following.
[0028] With respect to FIG. 2, given values include:
TABLE-US-00001 Pump flow rate V = 1300 .mu.l/s Probe inner diameter
id = 0.65 mm Probe inclination from vertical .phi. = 6.9.degree.
Vertical probe tip to hit point h = 27.868 mm Axial probe tip to
hit point l = 28.071 mm
[0029] The speed v.sub.0 of the liquid at the probe tip can be
derived from the pump flow rate and the needle inner diameter:
A = .pi. r 2 = .pi. ( 0.325 mm ) 2 = 0.332 mm 2 ##EQU00001## v 0 =
V . A = 1300 l / s 0.332 mm 2 = 1300 mm 3 s 0.332 mm 2 = 3915 mm s
= 3.91 m s ##EQU00001.2##
With reference to FIG. 2, the horizontal distance between the probe
tip and the cuvette wall can be calculated from:
s= {square root over (l.sup.2-h.sup.2)}
s=3.37 mm=3.37 10.sup.-3m
With reference to FIG. 3, the arc of the liquid stream can now be
calculated:
with h ' = v 0 t sin .alpha. ' - g 2 t 2 and t = s v 0 cos .alpha.
' ##EQU00002## h ' = s sin .alpha. ' cos .alpha. ' - g 2 ( s v 0
cos .alpha. ' ) 2 = s tan .alpha. ' - g 2 ( s v 0 cos .alpha. ' ) 2
= 2.78 10 2 m - 2.52 10 - 4 m ##EQU00002.2##
The first part of the term is equal to h and the second part gives
the difference between the ideal shown in FIG. 1 and actual hit
point.
[0030] Overall, there are four tolerance chains which can affect
the hit point: [0031] 1) Height tolerances--Tolerance summation of
parts which affect the vertical gap between the probe tip and the
cuvette top plane; [0032] 2) Axial tolerances--Tolerance summation
of parts which affect the horizontal or axial gap between the probe
tip and the central axis of the cuvette; [0033] 3) Angle
tolerances--Tolerance summation of parts which affect the probe
injection angle (any angle tolerances of the cuvette transport
system are considered to result in a height error and therefore are
considered part of the height tolerance chain); and [0034] 4)
Magnet array--Tolerance summation of parts which affect the
vertical distance between the cuvette and the magnet array
centerline.
[0035] In the following, every tolerance chain is treated
individually. Eventually, the total tolerance is estimated by
adding the results of the individual tolerance chains.
[0036] The calculations for the individual tolerance chains are
performed by executing the following steps:
[0037] Identification of related parts and their respective
tolerances, providing a graphical description of the tolerance
chain;
[0038] Graphical vector analysis of the tolerance chain;
[0039] Generation of a table of dimensions, tolerances, maximum
dimensions, minimum dimensions;
[0040] Calculation of the ideal closure dimension;
[0041] Calculation of the arithmetic maximum and minimum closure
dimensions and the arithmetic tolerance;
[0042] Identification of mean values from asymmetric tolerance
zones and means values of shape and positional tolerances;
[0043] Generation of closure dimension as distribution average;
[0044] Identification of deviation .sigma./variance .sigma..sup.2
for every dimension and calculation of the total error according to
the theorem of error propagation; and
[0045] Evaluation of statistical closure dimension and
tolerance.
[0046] The dimensions of all parts are considered to have normal,
Gaussian distributions with a deviation of .+-.3.sigma.. This means
that 99.73% of all parts are inside the tolerance zone. This
assumption is realistic for lot sizes of 60 to 100 parts and
greater. The shape and position tolerances have a folded normal
distribution.
[0047] For statistical calculation of the hit point tolerance, a
mathematical description of the hit point depending upon linear
position and angle of the probe is necessary. The arc of the liquid
stream is omitted at this point for simplicity, but is factored in
subsequently.
[0048] A simplified arrangement of a probe module and cuvette is
shown in FIG. 4. The draft or outward curvature of the cuvette wall
is omitted. h is the distance between the cuvette top plane and the
hit point on the inner wall of the cuvette. The width of the
cuvette is assumed to be constant. cw thus gives half the width of
the cuvette such that cw=2.73 mm.
h = h g - y ##EQU00003## and h g = x + cw tan .PHI. ##EQU00003.2##
h = x + cw tan .PHI. - y ##EQU00003.3##
The draft angle .beta., not taken into account in the foregoing, is
0.5.degree..
[0049] FIG. 5 illustrates the offset produced by the cuvette wall
draft. The value h.sub.r has to be deducted from h to get the
actual value of the hit point h.sub.real.
h real = h - h r ##EQU00004## with h r = l cos .PHI. ##EQU00004.2##
and l = h sin ( 180 .degree. - .beta. - .PHI. ) sin .beta. h real =
x + cw tan .PHI. - y - [ ( x + cw tan .PHI. - y ) 1 sin ( 180 -
.beta. - .PHI. ) sin .beta. cos .PHI. ] ##EQU00004.3##
(Eq. 1). Substituting the projected values from FIG. 1 into x, y,
and .phi. as control gives the correct value for h.sub.real, 25.98
mm.
[0050] Height tolerances are now considered with respect to FIG. 6,
which illustrates all parts which add tolerances in height. These
parts include a washer plate on which is mounted the acid injection
probe module, the probe module, a cuvette transport ring segment in
which the cuvettes are disposed, and a transport ring on which the
ring segments are disposed. The transport ring is supported by a
taper roller bearing and opposing circlips. Both the washer plate
and the taper roller bearing/circlips are supported upon an
incubation ring.
[0051] For the worst case in terms of height, it is assumed all
tolerances are at their maximum, so that clearance between the
washer plate and the cuvette is minimal. The hit point is thus
lowered towards the bottom of the cuvette. To achieve this, parts
of the left side of FIG. 6 must be at their minimum thickness
whereas the parts on the right side must be at their maximum
thickness. These requirements are illustrated in FIG. 6 by the
large arrows.
[0052] The vector diagram of FIG. 7 shows all dimensions with their
maximized or minimized direction. M0 is the so-called closure
dimension, or the vertical gap between the probe tip and the
cuvette upper plane. In the equations, this value is referred to as
y. The const. vector sums the two constant values shown in FIG. 6,
the thickness of the cuvette top plane and the vertical distance
between the probe tip and the washer plate.
[0053] In the following table, all factors with the respective
maximum and minimum values and resulting tolerance zones are
provided:
TABLE-US-00002 Max. Min. vector Dimension dimension G.sub.o
dimension G.sub.u Tolerance zone +const. 3.596 3.596 3.596 0 +M1 0
0.1 -0.1 0.2 -M2 90 90 89.95 0.05 +M3 6.15 6.17 6.13 0.04 +M4 1.75
1.75 1.69 0.06 +M5 15 15.2 15 0.2 +M6 1.2 1.2 1.14 0.06 +M7 52
52.04 51.96 0.08 +M11 0 0.2 -0.2 0.4 +M8 0 0.2 -0.2 0.4 +M9 5 5.1
4.9 0.2 +M10 3 3.1 2.9 0.2
[0054] The nominal closure dimension M.sub.OH:
M 0 H = M i + - M i - ##EQU00005## M 0 H = 3.596 + 0 - 90 + 6.15 +
1.75 + 15 + 1.2 + 52 + 0 + 0 + 5 + 3 = - 2.304 ##EQU00005.2##
[0055] The arithmetic maximum closure dimension y.sub.max:
y max = G o i + - G u i - ##EQU00006## y max = ( 3.596 + 0.1 + 6.17
+ 1.75 + 15.2 + 1.2 + 52.04 + 0.2 + 0.2 + 5.1 + 3.1 ) - 89.95 = -
1.294 ##EQU00006.2##
[0056] The arithmetic minimum closure dimension y.sub.min:
y min = G u i + - G o i - ##EQU00007## y min = ( 3.595 + ( - 0.1 )
+ 6.13 + 1.69 + 15 + 1.14 + 51.96 + ( - 0.2 ) + ( - 0.2 ) + 4.9 +
2.9 ) - 90 = - 3.184 ##EQU00007.2##
[0057] The arithmetic closure dimension with tolerance zone is
thus:
M 0 H = y = 2.304 + 0.88 - 1.01 ##EQU00008##
[0058] Some statistical calculations are necessary to account for
component fluctuations. The mean values from asymmetric tolerance
zones M2, M4, M5 and M6 are now defined. For M2:
.mu. 2 = 90 + 89.95 2 = 89.975 ##EQU00009##
Similar calculations for M4, M5, and M6 yield:
.mu..sub.4=1.72
.mu..sub.5=15.1
.mu..sub.6=1.17
[0059] As for M1, M8, and M11, shape and positional tolerances are
distributed with a folded normal distribution. Mean values and
deviations must therefore be calculated with the following
equations. A deviation of 3.sigma. is thereby assumed.
.sigma. 1 = F 1 3 = 0.2 3 = 0.066 .mu. F 1 = 2 .sigma. 1 2 .pi. =
0.053 .sigma. F 1 = 1 - 2 .pi. .sigma. 1 = 0.04 M1 .sigma. 8 =
0.133 .mu. 8 = 0.106 .sigma. F 8 = 0.08 M8 .sigma. 11 = 0.133 .mu.
11 = 0.106 .sigma. F 11 = 0.08 M11 ##EQU00010##
[0060] The closure dimension .mu..sub.0H is calculated as a
distribution average:
3.596 + 0.053 - 89.975 + 6.15 + 1.72 + 15.1 + 1.17 + 52 + 0.106 +
0.106 + 5 + 3 = - 1.974 ##EQU00011##
[0061] The deviation .sigma..sub.0H of the closure dimension:
0.04 2 + ( 0.05 6 ) 2 + ( 0.04 6 ) 2 + ( 0.06 6 ) 2 + ( 0.2 6 ) 2 +
( 0.06 6 ) 2 + ( 0.08 6 ) 2 + 0.08 2 + 0.08 2 + ( 0.2 6 ) 2 + ( 0.2
6 ) 2 = 0.135 ##EQU00012## T SH = 6 .sigma. 0 H = 0.81
##EQU00012.2##
[0062] The statistical closure dimension with tolerance zone
is:
M.sub.0H=y=.mu..sub.0H.+-.(T.sub.SH/2)=1.974.+-.0.405
[0063] Axial tolerances are now considered. FIG. 8 illustrates the
components which contribute tolerances in the axial direction. The
worst case is reached if the probes are displaced towards the
inside of the incubation ring and the cuvette is displaced away
from the probes. The large arrows in FIG. 8 illustrate these
conditions.
[0064] The vector diagram of FIG. 9 the various contributing
factors with the respective direction. M0 is the closure dimension,
here the horizontal gap between the probe tip and the cuvette
centerline. In the equations that follow, this value is identified
as x.
[0065] The const. vector is the constant value shown in FIG. 8 and
represents the horizontal distance between the probe tip and the
cuvette centerline. The tolerance of this separation can be
neglected due to the construction of a preferred instrument.
[0066] In the following table, all of the contributors with their
maximum and minimum dimensions and tolerance zones are
provided.
TABLE-US-00003 Max. Min. Vector Dimension dimension G.sub.o
dimension G.sub.u Tolerance zone -const. 0.3 0.3 0.3 0 -M11 23.03
23.13 22.93 0.2 +M12 226 226.02 225.98 0.04 -M13 0 -0.05 0.05 0.1
-M14 215.87 215.92 215.82 0.1 +M15 14.12 14.22 14.02 0.2
[0067] The nominal closure dimension M.sub.0A is given by:
M 0 A = M i + - M i - - 0.3 - 23.03 + 226 - 0 - 215.87 + 14.12 =
0.92 ##EQU00013##
[0068] The arithmetic maximum closure dimension x.sub.max is given
by:
x max = G o i + - G u i - ( 226.02 + 14.22 ) - ( 0.3 + 22.93 + 0.05
+ 215.82 ) = 1.14 ##EQU00014##
[0069] The arithmetic minimum closure dimension x.sub.min is given
by:
x min = G u i + - G o i - ( 225.98 + 14.02 ) - ( 0.3 + 23.13 + ( -
0.05 ) + 215.92 ) = 0.7 ##EQU00015##
[0070] From these values, the arithmetic closure dimension with
tolerance zone is given by:
M 0 A = x = 0.92 + 0.22 - 0.22 ##EQU00016##
[0071] Some statistical calculations are necessary to account for
component fluctuations. The mean values for shape and position for
tolerance M13 are now defined.
[0072] M13: .sigma..sub.13=0.033 .mu..sub.F13=0.027
.sigma..sub.F13=0.02
[0073] Closure dimension .mu..sub.0A is given as a distribution
average:
-0.3-23.03+226-0.02-215.87+14.12=0.9
[0074] The deviation .sigma..sub.0A of the closure dimension is
determined from:
( 0.2 6 ) 2 + ( 0.04 6 ) 2 + 0.02 2 + ( 0.1 6 ) 2 + ( 0.2 6 ) 2 =
0.054 ##EQU00017##
[0075] The statistical closure dimension with tolerance zones is
given by:
M.sub.0A=x=.mu..sub.0A.+-.T.sub.SA/2=0.9.+-.0.162
[0076] Injector inclination tolerances are now addressed. The
tolerance of the bores in the washer plate is M16=.+-.0.05.degree..
The parallelism of the axis of the probe bore and the axis of the
injector outer diameter is M17=0.05 mm. With the length of 18 mm
this results in an angle tolerance of:
TABLE-US-00004 .PHI. = M 16 + arctan ( M 17 18 ) ##EQU00018## Max.
Min. Vector dimension dimension G.sub.o dimension G.sub.u Tolerance
zero M16 6.9.degree. 6.95.degree. 6.85.degree. 0.1.degree. M17 0
0.05.degree. -0.05.degree. 0.1.degree.
[0077] The nominal angle .phi..sub.0 is given by:
.PHI. 0 = 6.9 .degree. + arctan ( 0 18 ) = 6.9 .degree.
##EQU00019##
[0078] The arithmetic maximum angle .phi..sub.max is given by:
.PHI. max = 6.85 .degree. + arctan ( - 0.05 18 ) = 6.69 .degree.
##EQU00020##
[0079] The arithmetic minimum angle .phi..sub.min is given by:
.PHI. min = 6.95 .degree. + arctan ( 0.05 18 ) = 7.11 .degree.
##EQU00021##
[0080] The closure dimension with tolerance zone is thus given
by:
.PHI. 0 = .PHI. = 6.9 .degree. + 0.21 - 0.21 ##EQU00022##
[0081] Some statistical calculations are necessary to account for
component fluctuation. The mean values for shape and position for
tolerance M17 are now defined.
[0082] M17: .sigma..sub.17=0.033.degree. .mu..sub.F17=0.027.degree.
.sigma..sub.F17=0.02.degree.
The average angle distribution .mu..sub.0.phi. is given by:
.mu. 0 .PHI. = 6.9 .degree. + arctan ( 0.027 .degree. 18 ) = 6.986
.degree. ##EQU00023##
[0083] The deviation of the angle error is given by:
.mu. F 17 = 0.027 .degree. .sigma. M 16 = ( 0.1 .degree. 6 )
.sigma. F 17 = 0.02 .degree. ##EQU00024## .sigma. 0 .PHI. = [ M 16
( M 16 + arctan ( .mu. F 17 18 ) ) ] 2 .sigma. M 16 2 + [ .mu. F 17
( M 16 + arctan ( .mu. F 17 18 ) ) ] 2 .sigma. F 17 2
##EQU00024.2## .sigma. 0 .PHI. = 0.017 .degree. ##EQU00024.3## T S
= 6 .sigma. 0 = 0.102 .degree. ##EQU00024.4##
[0084] The statistical angle error with tolerance zone is thus
given by:
.PHI. 0 = .PHI. = .mu. 0 .+-. T s 2 = 6.9 .degree. .+-. 0.05
.degree. ##EQU00025##
[0085] The worst case calculation for hreal can now be calculated
by setting the arithmetic maximum values for x.sub.max, y.sub.max,
and .phi..sub.max into Eq. 1, above.
x max = 1.14 ##EQU00026## y max = 1.294 ##EQU00026.2## .PHI. max =
6.69 .degree. ##EQU00026.3## h real = x + cw tan ( .alpha. ) - y -
[ ( x + cw tan ( .alpha. ) - y ) 1 sin ( .pi. - .beta. - .alpha. )
sin ( .beta. ) cos ( .alpha. ) ] ##EQU00026.4## h real = 29.504
##EQU00026.5##
[0086] The arithmetic minimum can be calculated using the
analog:
x min = 0.7 ##EQU00027## y min = 3.184 ##EQU00027.2## .PHI. min =
7.11 .degree. ##EQU00027.3## h real = x + cw tan ( .alpha. ) - y -
[ ( x + cw tan ( .alpha. ) - y ) 1 sin ( .pi. - .beta. - .alpha. )
sin ( .beta. ) cos ( .alpha. ) ] ##EQU00027.4## h real = 22.725
##EQU00027.5##
[0087] Thus, the arithmetic derivation of the hit point with
tolerance zone is given by:
h real = 25.98 + 3.52 - 3.25 ##EQU00028##
[0088] The hit point .mu..sub.h as distribution average with
.mu..sub.0H=1.974, .mu..sub.0A=0.9, .mu..sub.0.phi.=6.986.degree.
and employing Eq. 1:
.mu..sub.h=25.812
The statistical deviation .sigma..sub.h of the hit point, depending
upon the variables .sigma..sub.0A, .sigma..sub.0H,
.sigma..sub.0.phi., can now be calculated using Eq. 1. Using
partial derivatives at the distribution average:
.sigma. h 2 = ( .differential. h real .differential. x ) 2 .sigma.
0 A 2 + ( .differential. h real .differential. y ) 2 .sigma. 0 H 2
+ ( .differential. h real .differential. .PHI. ) 2 .sigma. 0 .PHI.
2 ##EQU00029##
With .mu..sub.0H=1.974, .mu..sub.0A=0.9,
.mu..sub.0.phi.=6.986.degree. and .sigma..sub.0H=0.135,
.sigma..sub.0A=0.054, and .sigma..sub.0.phi.=0.017.degree., the
result is:
.sigma..sub.h=0.435
T.sub.SH=6.sigma..sub.h=2.61
[0089] The statistical error of the hit point with tolerance zone
is thus given by:
h real = 25.98 .+-. T SH 2 = 25.98 .+-. 1.305 ##EQU00030##
[0090] In the embodiment in which the pellet is formed by a magnet
array, the tolerance of the array relative to the cuvettes must
also be accounted for. The magnets, in a preferred embodiment, are
fixed in a ring which is suspended under the transport ring. Most
of the tolerance of the magnets is addressed in the height
tolerances previously calculated. Thus, there are only the
following tolerances to be accounted for:
[0091] M18--slide bearing;
[0092] M19--magnet ring (i.e. the position of the magnet assembly
in the magnet ring);
[0093] M20--magnet assembly (i.e. the tolerance of the fixture into
which the magnet assembly is fixed); and
[0094] M21--the slide bearing support.
All of the above contribute to movement in the same direction.
TABLE-US-00005 Min. Tolerance Vector dimension Max. dimension
G.sub.o dimension G.sub.u zone M18 4 4.1 4.05 0.05 M19 7.4 7.45
7.35 0.1 M20 0 0.05 -0.05 0.1 M21 1 1.1 0.9 0.2
[0095] The nominal closure dimension M.sub.0M is given by:
M.sub.0M=.SIGMA.M.sub.i
4+7.4+1=12.4
[0096] The arithmetic maximum closure dimension P.sub.0M is given
by:
P.sub.0M=.SIGMA.G.sub.0i
4.1+7.45+0.05+1.1=12.7
[0097] The arithmetic minimum closure dimension P.sub.0M is given
by:
P.sub.0M=.SIGMA.G.sub.0i
4.05+7.35-0.05+0.9=12.25
[0098] The arithmetic closure dimension with tolerance zone is thus
given by:
M 0 M = 12.4 + 0.3 - 0.15 ##EQU00031##
[0099] Mean values from asymmetric tolerance zone M18 is given
by:
.mu..sub.18=4.075
[0100] The closure dimension .mu..sub.0M as a distribution average
is found according to:
5.075+7.4+1=12.475
[0101] The deviation .sigma..sub.0M of the closure dimension is
given by:
( 0.05 6 ) 2 + ( 0.1 6 ) 2 + ( 0.1 6 ) 2 + ( 0.2 6 ) 2 = 0.042
##EQU00032## T SM = 6 .sigma. 0 M = 0.252 ##EQU00032.2##
[0102] The statistical closure dimension with tolerance zone is
thus:
M 0 M = .mu. 0 M .+-. T SM 2 = 12.475 .+-. 0.126 ##EQU00033##
[0103] The nominal distance between the magnet centerline and the
cuvette top plane at the acid injection position is 31.72 mm. This
value can be calculated with the nominal dimensions listed
above:
3.9+12.4+6.35+5+3+1.067=31.717
(3.9 being the distance between the upper magnet and the magnet
ring, 6.35 being the magnet width).
[0104] The deviation .sigma..sub.h and the tolerance zone T.sub.SH
of the hit point relative to the cuvette top plane was estimated
above as 25.98.+-.1.305 mm. The nominal measure between hit point
and magnet centerline is thus:
h.sub.total=31.717-25.98=5.737
[0105] The total deviation .sigma. of the difference between hit
point and magnet centerline is thus calculated by:
{square root over (0.435.sup.2+0.042.sup.2)}=0.437
T.sub.s=6.sigma.=2.622
[0106] The statistical error of the hit point versus magnet
centerline with tolerance zone can then be written as:
h total = 5.737 .+-. T s 2 = 5.737 .+-. 1.311 ##EQU00034##
Once 0.25 mm is added to compensate for the arc of the liquid
stream, the acid injection is calculated to hit the cuvette wall
not deeper than 4.167 mm above the magnet centerline.
[0107] One embodiment of a probe housing 100 is illustrated in FIG.
10. This housing, which supports dual probe nozzles 102 is mounted
in order to direct a parallel stream of liquid, preferably acid,
above a pellet of particles such as paramagnetic particles which
have accumulated on the interior wall of a reaction vessel such as
a cuvette. By following the tolerance analysis procedure detailed
above, the hit point for both acid streams can be assured to be
above the pellet, regardless of variations in the physical
components of the system.
[0108] The linear dimensions in FIGS. 11, 12 and 13 are all given
in millimeters. A front view of the probe housing 100 is provided
in FIG. 11, showing the mutually adjacent nozzles which produce
parallel streams of resuspension liquid. In FIG. 12, a
cross-section taken along lines A-A in FIG. 11, it can be seen that
ideally a source of resuspension liquid is coupled to the back of
the probe housing. As can be seen in FIG. 13, a cross-section taken
along lines B-B of FIG. 11, the liquid source feeds both nozzles
102 in generating the parallel streams, five millimeters apart.
[0109] On the back of the probe housing 100 is a mounting recess
110 for interfacing to a resuspension liquid-supplying conduit (not
shown). Secure attachment of the conduit to the housing 100 is
preferably through interlocking threads or other means known to one
skilled in the art. Preferably a buffer zone 112 exists between the
forward end of the conduit once installed in the recess 110. Liquid
from the conduit passes into the buffer zone and then into each of
two channels 114 which lead to respective probes 116 and the probe
nozzles 102 themselves. In the illustrated embodiment, the probes
116 and nozzles 102 are 0.65.+-.0.02 mm in diameter.
[0110] Having described preferred embodiments of the presently
disclosed invention, it should be apparent to those of ordinary
skill in the art that other embodiments and variations
incorporating these concepts may be implemented. Accordingly, the
invention should not be viewed as limited to the described
embodiments but rather should be limited solely by the scope and
spirit of the appended claims.
* * * * *