CA2178064A1 - Method and apparatus for aspirating and dispensing sample fluids - Google Patents

Abstract

A method and apparatus for aspirating and dispensing a sample fluid. The apparatus includes an air source having an output port coupled to a first port of a flow through pressure transducer. A
second port of the flow through pressure transducer is coupled to a first port of a sample probe. The flow through pressure transducer provides transducer signals to a detector circuit. In response to the transducer signals provided thereto, the detector detects the occurrence or non-occurrence of a plurality of different events.

Description

1 FIELD OF THE INVEN'I'IO1V

2 The invention relates to the field of automated fluid sample 3 devices and more particular~~.y, to apparatus for detecting when a 4 sample probe of an automated fluid sample sy item contacts a liquid.
BACKGROUND OF_ THE INVE,NT:LON
6 As is known in the art, automated ~inalyzers are used in 7 clinical laboratories to measure th.e various chemical constituents 8 of body fluids, such a.s whole blood, bl;~od serum, blood plasma, 9 cerebral spinal fluid, urine; and the liked obtained from patients.
Automated analyzers reduce the number of trained technicians 11 required to perform the analyses in a clinical laboratory, improve 12 the accuracy of the testing ,Inca reduce the ~::ost per test .
13 Typically, an automated analyzer includes an automated fluid 14 moving system which automatically aspirat.~~s ,:~ sample of body fluid from a patient's specimen container and dispenses the sample into 16 a reaction cuvette. The fluid zn.ovi.ng systez~~ typically includes a 17 pipette which accomplishes the aspirate and dispensing functions 18 under the control of a robot:i.c ar_m.
19 Chemical reagents, which are specific to the test being performed, are disposed into the sample-cont~-zining cuvette thereby 21 mixing the sample with the ~:hemical reagents . By examining the 22 reaction products resulting from the mixing of the sample and 23 reagents, the automated analyzer determines the concentration of 24 the specific chemical. constituent, for which the testing is being performed, in the pat:ient's spec.i.mer~. j.Tpon completion of the test, Wf;INCAH'I'IiN. S<'HURGIN.
liA<iNi-:81N & HAYF,S
'1'1'.I, (617) 542 =:'.'N) IvA7i (617) a51-~Ytl?

~'~~
1 the automated analyzer typically prinis t:he results of the test, 2 including a sample identifier, a numerical o°esult of the test, and 3 a range of values for the chemical consta.tuent as measured by the 4 test.
During an aspiration operation, the robc~ti.c arm, under command 6 of a system controller, positions the pipette above a specimen 7 container and moves the pipette into t:he container until the 8 pipette reaches the fluid in the c:ontaine:rv. A syringe type pump is 9 than typically operated to draw sample fl~zid from the specimen container into the pipette.
11 One problem that occurs with the fl.u:.~d moving systems is that 12 occasionally upon aspirating a sample, t:~m sample pipette~fails to 13 be properly disposed in the sample to be aspirated. In this case 14 air_, rather than a patient ;specimen, is drawn ::Lnto the pipette.
This prevents the necessary sample vo:Lum~i.e of the fluid specimen 16 from being aspirated or from being completely dispensed into the 17 reaction cuvette. If an improper sampli~ volume of specimen is 18 mixed with the reagents, an incorrect test. resazlt will typically be 19 obtained.
Generally, when a clinician obtains an unusual test result, 21 the test is repeated arzd the new result u~orxxpared to the previous 22 result. If the two results do not agree to within a predetermined 23 limit, the test mast be repeated a sE:~cond time in order to 24 determine which of the previcaus two x~esul is is valid.
Thus, it would be desirable to provide an automated fluid 26 sample aspiration/dispensation device whack detects physical _ 3 .
~VL~:INGAR'fH:N, SY'HlIRGIN, f)AGNE:fiIN & HAYf~.S
'f 1=.i. (61 ~ 542~32~X1 1>nx (s177 asW si?

1 contact between a probe tip and a surface of a liquid to thus 2 ensure that a fluid rather than. air is drawn in to the sample 3 probe.
4 SUMMARY OF 'fH>:: :INVET~"TIUN
In accordance with the present invention, an apparatus for 6 aspirating and dispensing a sample fl.ui;_~ ~ ncludes an air source 7 having an output port coupled i:c an input ~~ort of a flow through 8 pr~=ssure transducer. Ari output: of thl: :blow through pressure 9 transducer is coupled to a sample probe wrnich has a tip that contacts the sample fluid. With this particular arrangement an 11 apparatus for detecting physical contact between the sample probe 12 and a surface of a 7_iquid sample is ~>rov~zded. The pressure 13 transducer senses pressure chances which result from a number of 14 other events including but not limited t;c~: (a) fluid leaks in a fluid path; (b) aspiration through the sample probe; (c) 16 obstruction of a sample probe tip; arzd (d) attachment and 17 detachment of a sample tip t::o a sample p:_robe s The apparatus may 18 also include a detector circuit corzpled r_~, the transducer. In 19 response to each of the abovc~~identified evl'.nts, the flow through pressure transducer provides a differential voltage signal to the 21 detector circuit, 22 In a surface detection mode of oper~.ti.on the air source 23 provides a constant ait:~ flow the~c~ugh the pressure transducer and 24 the sample probe, and probe tip while the sample probe is being lowered toward a surface of a fluid. Unce the sample probe tip _ 4 _ WIv.IN(:AR'1'I~',N. S('HURCIN.
(~AniNE;BIN & HAYI?.S
'fF:l. (6171 S4~_~-?_~(1 PAX (61'n 4$1-0;i1;1 1 reaches the surface of the l.iqu:~_d, the pressure transducer senses 2 a change in pressure of t:he air path yin which the pressure 3 transducer is disposed. In response to tine pressure change the 4 transducer provides transducer signals too the detector circuit.
The detector circuit det:ect.s t:rze signals provided thereto and 6 provides a control signal to a system coritro7_ler.
7 The detector r_i.rcuit may be provided with the capability to 8 detect several events including but not liz~uited to: leaks; fluid 9 level; aspirate integrity; clots; tip pr~::sence and pump servo integrity. Each of the events result in :~_dentifying signals being 11 provided to a system controller fc~r c:ontx~r;~l .:of the air pump and the 12 sample probe.
13 In detecting the position of a surface of a fluid, a sample 14 probe is moved toward a fluid surface and when contact is made, a change in pressure i.n the a:ir path in7.irm with the flow through 16 pressure transducer provides a pressure transducer signal 17 representative of the contact, further permitting determination and 18 the location of the fluid surface.
19 Leaks in a fluid path of an aspirate and dispense apparatus uses the same apparatus operated to occlude t:he sample probe tip by 21 inserting the sample probe ti.p into a sample fluid and sensing the 22 signal provided by the pressure transducer. A sensed pressure below 23 a normalized pressure indicates leaks ~.n the fluid path of the 24 aspirate and dispense apparatus. Tf a leak exists the pressure will not: rise to the normal level each time. ~'tne mormal pressure can be 26 established by placing a calibration t~~:~ having no opening for _ , _ WIIN(iARTI:N, S<'HIIRUIN, (:AGNIiRIN &. HAYf:S
'1"L;I. 1617) .54? .390 FAX (6171 451-0313 1 aspiration onto the sample probe body.
2 The detector circuit also d~~t:ects wneia a sample probe tip is 3 being coupled to a sample probe at a tip loader and removal of the 4 sample probe tip at a tip dispense position by the increase in pressure when the smaller. tip opening i ~ Lylaced over the sample 6 probe. The detector circuit a.l.~cz de=tectr.:when a sample probe tip 7 is occluded by an obstruction during an aspirate or dispense 8 operation. The occlusion must be severe enough to trigger a 9 predetermined pressure change in the pre~~sure transducer. The detector circuit also provides an indicat:~.on whether a system bleed 11 va:Lve is closed or open. The df~Cector c~i rcui.t also evaluates the 12 pump servo integrity by comparing the voltage on the air pump 13 vo_Ltage with a voltage of the pressure tra.n.sducer in the tubing and 14 determining whether the voltage x°E.ala.t;ionship is within predetermined limits. The detector ~v.ir~~,~uit also determines 16 aspirate integrity by verifying that an a.ir aspiration results in 17 a pressure change within predet:.ermi.ned 1_ ~.mit: s .
18 BRIEF L'1ESCRIPTIUN OF THE L7R~WINGS

19 This invention is pointed out wit.r; particularity in the appended claims. The above and furC:~ner advantages of this 21 invention may be bettez: understood y rE~~~ex.ring to the following b 22 de:~cription the ac c.:ompanying drawing, taken in in conjunction with 23 which:

24 FIG. 1 is a block diagram of an automated fluid sample aspiration/dispensation apparatus;
WGINUAK'I'EN, S<'HUKCIIN, fiAC;NEBIN fi HAYFS
'I'1:1. (617) S4? 3_N0 I'AX (617f 451-0zl?

1 FIG. 2, is a diagx~ammata.ca.J_ view of: a~n automated fluid sample 2 aspiration/dispensation apparatus;
3 FIG. 3 is a b)_ock diagram ca f: a detector system; anct 4 FIG. 4 is a schematic diagram of detector circuits for various functions.
6 Referring now to FIG. 1, aspirating and dispensing apparatus 7 includes a constant air source 12 having a.n output port 12a coupled 8 through a two way bleed valve 14 to a first. port 16a of a three way 9 pump valve 16. Bleed valve 14 has a vent 14y which is controlled by bleed valve 14 t.o be open on closed awe described below.
11 The constant air source 12 should be of a type capable of 12 providing a constant air flow at a predetF~rmined rate and pressure 13 to the pump valve 1E> . This rate and pz:~f~5sure ~s fairly low and 14 depends on overall system parameters.
A second port ~L6b of pump va:Lve 16 :is ccaupled to a first input 16 port 18a of a T-junctian 18 and a third part 16c of the valve 16 is 17 coupled to a vent. A second part 18b of th=:-~ T-junction connector 18 18 is coupled to a sample probe diluter .?0 which may be provided 19 for example as a syringe or ~?umped dilutes c,ource.
A third port 18c of T-junction conraf.;ctor 1F3 is coupled to a 21 flow through pressure transducer 22 at a first port 22a. A second 22 port 22b of the transducer 22 is r_,aupled ~:1~ a sample probe 24 which 23 may, for example, be provided as a pipette tube holder. Thus the 24 pressure transducer 22 is ).orated in-line with a fluid conduit between the air source 12 and the sample probe 24.
26 The pressure transducer 22 :is p.referaLoly Located proximate the WI-;IN(iAK'1'L:N. 1('.HUK<:IN.
(7AUNF;HiN St HAYC~'.,S
'I'lil. (617) 54~ ?2911 PAX (617) 45111313 1 sample probe 24 to thus improve the signal to noise ratio of the 2 pressure measurement. The sample probe 24 is controlled by a robot 3 arm 23 to move to and/or from a cuvette 31 to aspirate or dispense 4 in an automated assay system or to/from a tap stations 25 and test tube 27. In response to fluid fl. ow through. the px.~essure transducer 6 22 the transducer provides an electrical signal through a signal 7 line 26 to a detector system 28. T:f~e det.e~c~tl~z° circuit 28 receives 8 input signals from the transducer 22 and prop°ides output signals to 9 the air source 12 and to a microprocessor based control system 33 via a microprocessor bus 30.
11 The detector system 28 detects r_he occurrence or non-12 occurrence of different events throuc~noL~t arz analyzer cycle 13 automated analyzer system.
14 In response to the input signals from ~:he transducer 22, the detector system 28 provides a plurality of functions to indicate by 16 appropriate output signals when a distal end of the sample probe 17 24, typically having a pipette tip, physically contacts a fluid 18 sample 31 disposed in tube 2'7 or r_mvette 32 into which the sample 19 probe 24 is lowered by arm 23.
FIG. 2 shows in more detail. the syst.enA e~f FIG. 1. As shown 21 therein an aspirating and dispersing appar°atus includes constant 22 air source which here includes an air pump 70 coupled to an 23 accumulator 72 having a vessel ~n which air provided from the air 24 pump 70 is stored at a particular pressurve such that a supply of air at a constant, low pressure is immediately available at an 26 output port 72a of the accumua_ator . In ths.s ,~aarticular embodiment, _ 3 _ W1~;IN(.iAH'I'I>N, scHUk(~1N.
l~A~.NENIN Re HAYI~:.V
'1'f:1. (617) Sd~-2~!)U
PnX (61~ 4ill)~IS

1 the accumulator 72 is provided as a coal cof tt.zbing 73 which acts to 2 regulate the pressure and ~wariable flow rates and is diminished 3 according to the needed slow regulation zn pressure measurement.
4 A three port connecting member 74 disposed between the coil 73 and the air pump 70 has a first port couple. to the output port of 6 the air pump 70 and a second port coupled too a first port of the 7 coil 73. A third port of them connecting member '74 provides a vent 8 port to which is coupled a vent tube '76.
9 To ensure proper operation of the aspa_rating and dispensing apparatus, the air pump 70 provides a relatively low air flow at 11 the output port 72a of the accu.mul.ator 72. To provide such an air 12 flow connecting member 24 vents a portion of the flow from air pump 13 70.
14 The vent tube 76 may preferably be provided as part of the coal 73 (e.g. proW _ded on an inside port~~.or~ the accumulator coil 16 73j. The vent 76 establishes an upper pressure limit to which the 17 pump 70 will be exposed even in the case of complete occlusion of 18 the sample probe.
19 The accumulator 72 may alsc7 be i.mplemerzted using other techniques well known to those of ordinary skill in the art.
21 The accumulator output port. 'T2a is co~.,zpled througrz a bleed 22 valve 14 to a common port 80a of pump valve 80 corresponding to 23 pump valve 16 . The pump va~_ve 80 also i ~ic.Lvzdes a normally open 24 port 80b to the sample probe and a normatly ~~losed port 80c to a vent 80d. The pump valve 80 is c.=on.trolleci r:sy a controller 94.
26 The port 80b of pump valve 80 is coupled to a first port 82a W61NCARTIiN. SCHURCI1N, (IAC:~NI:$IN .k~ HAYI;S
TFI. (6171 542-~_~_911 PAX (617) 45111313 1 of a three port connecting member 82. A second port 82b of the 2 three port connecting member 82 is coupled to a diluter 84. The 3 diluter 84 may be provided for example t~.~ a syringe pump in which 4 the movement of a piston f36 .in a fa.rst direction forces fluid from a housing 88 while movement of the pistozr 86 in a second opposite 6 direction pulls fluid into the housing 88 through port 82b.
7 A shaft 90 couples the piston 86 to a linear stepper motor 92.
8 In response to signals rece3.ved from ccfnt~voller 94, the stepper 9 motor 92 drives t:he pisto:~z 8e~ i.m fixst and second opposite directions within the housing X38. Irz a preferred embodiment, the 11 controller 94 is provided as a microprocessor based controller.
12 A third port 82c of tha three port c~~nnecting member 82 is 13 connected to a tube 96 having an :i..nner diameter which fits the port 14 82c sealing the connection.
A pressure transducer c~8 has a first port 98a coupled to a 16 second end of the tube 96 and a second por°t ~~ 8b coupled to a f first 17 end of a typically resilient tube 100. A second end of the tube 18 100 is coupled to a first port of a. sam~,~l.e probe 102. Thus the 19 connecting element 82 and tubes 9E~, 100 aiud pressure transducer 98 provide a fluid path between the sample: pa:obe 102 and the pump 21 valve 80 and diluter 84.
22 The pressure transducer 98 is here provided as a flow through 23 pressure transducer of the type rnanufact~.zz:ed by the Micro Switch 24 Division of Honeywell Corporation and i.dent:i.fied as a 26PC Series pressure transducer and more particularly as part number 26PC BFG
26 6G. The sensitivity of the transducer 98 corresponds to about 10 W1~:IN(iAk~('I:N. St'HIJktiLN.
tiA(.INI:HIN ~ HAYf;iS
rla, tel7> Sa. ~z~tl FA\ ~EI'n 451-t131a 1 mV/PSI of pressure differencva. Gtlmz: glow through pressure 2 transducers having suitable f=t.nzid and e:_ectrical charar_teristics 3 ma.y also be used.
4 To facilitate connecting of the transducer ports 98a, 98b to the respective ones of the t:.ubE=.s 96, 1~)0 with substantially 6 different diameters, each of the ports 98a, 98b has coupled thereto 7 a mating tube 101. The mating tubes 10:~ are provided from a 8 relatively flexible material. having a r~:.~.atively high elasticity 9 characteristic and a non-stretched diameter selected to accept the outside diameter of the tubes 9(~, 100 wu.th a slight interference 11 fit.
12 The sample probe 102 includes a probe body having a channel 13 110 between a first f_.luid port 10~a to wh~cr~ the system tubing 100 14 is coupled and having a second fluid pord 706b to which a sample probe tip 108 is coupled. In tYLis pay°ti,:ul.ar embodiment, the 16 sample probe tip 108 is provided as a disposable sample probe tip 17 which is removably coupled to the sample probe body 106. It should 18 be appreciated, however, that in some applications it may be 19 desirable to provide the sample probe t:ixas a non-disposable plastic tip which is permanently secured to the sample probe body 21 106.
22 The tube 100 which couples tL~e t;ransdtxcer 98 to the sample 23 probe 102 is here provided having a :LengtY~ typically of about nine 24 and one-half inches. It is des:irabl.e to cnz.nimize the distance between the sample probe 102 arid the 'pressure transducer 98. In 26 some applications, it may be desirable or even necessary to place - ~_ 1 ..
WEINGAR'CCiN. Sl'.HUkCiIN, fIAC:NEIiIN ~ HAYF;.S
TEL <617) 542-290 1~Ah f617) 4511Yi13 1 the pressure transducer 98 closer than nirxe and one-half inches 2 from the sample probe 102 and as close as possible to the sample 3 probe 102.
4 In applications in which it. is desirable to maximize sensitivity of the apparatus 6~ to small changes in pressure, for 6 example, it would be desirable t.ro directly mate the transducer 98 7 to the sample probe 102. In prac=tical applia:ations, however, it is 8 often not possible due the size of circuit ccamponents and available 9 packaging space to achieve this goal. Thn.~s, as trade-off, the pressure transducer 98 should be coupled to the sample probe 102 11 via a tube which minimizes the length of the fluid path between the 12 transducer 98 and the sample prof>e 102.
13 For this purpose the pressure transducer 98 may be disposed on 14 a printed circuit board (PCB) coupled to the sample probe 102 or as mentioned above, if space permits the pressure transducer may be 16 directly disposed on the sample probe 102_ 17 In this particular embodiment the flow through pressure 18 transducer 98 has a. pair of eler_:tr:ical. t;~:~rnuinals 98c, 98d one of 19 which corresponds to a positive output termi~ual and one of which corresponds to a negative output terminal of the transducer 98.
21 The transducer 98 provides a differential output voltage on the 22 output terminals 98c, 98d representative of the pressure difference 23 between the pressure in the sample probe tip and an ambient 24 atmospheric pressure.
The transducer 98 i.s electri.cal.ly coupled through lines 111 to 26 a detector circuit 112 at a pair of inp~.~t termi..nals 112a, 112b.

W1~;IN<;Ak'1'L:N, S'~'HUk(~IN.
GA(iNFRIN & HAYFS
~rrl. t~sm say z2m Fnx cey asi ~oi~

1 The detector circuit 112 rec~.eives input ;aic3nals from the pressure 2 transducer 112 and provides at :~.ts output tc-~rminals output signals 3 to controller 94 and to the air pump '70.
4 In operation, prior to aspirating a sample fluid from a tube 27 or cuvette 32, the vent port 80c of pum~;~ valve 80 i.s initially 6 closed and the common and sample ~>robe poxt.s 80a, 80b are initially 7 open. Also, the vent port: of the bleed valve 78 is closed and the 8 piston 86 is positioned so that no fluid :LS inside the housing 88.
9 The air pump 70 is then turned ran, f_orcing ai r through a fluid path which leads to the sample probe= tip 108x. "thus air is forced out 11 of the sample probe tip at a predetermineck rate which creates a 12 predetermined pressure measured by Pressure Transducer 98.
13 The sample probe 106 is mczved toward a region in which fluid 14 is expected to be contacted such as :in the tube 27. When the sarnple probe tip 108a initially contacts f:Luid, the tip 108a is 16 occluded by the fluid. This results in the fluid conduit coupled 17 between air pump 70 and the sample probe tip 108, including fluid 18 limes 96, 100, being pressurized. The px:essure transducer 98 19 senses the increased pressure level arrcl ~;irovides a transducer signal to the detector circuit 1.12.
21 The detector circuit 112 then provides a control signal to the 22 controller 94 which stops the sample po:~c:~be from being lowered 23 further or beyond a preset po~.nt into th~~~ fluid samp:Le. The 24 controller 94 provides control signals to copen the vent port of the bleed valve 78 to thus de-pressurize the f a.uid path between the air 26 pump 70 and sample probe 102 including the fw..uid path in which the - 1. 3 ._ WI:INGAR'I'GN, S('HUR(:IN.
GAGNI:BIN & HAYES
'PF;I. (617) 542-2~'Xl I~AX (617) 45141,'tlz 1 pressure transducer 98 is disposed.
2 After the fluid lines have been de-pressurized, the controller 3 94 closes the vent port of tree bleed valve 73. De-pressurizing the 4 fluid path between. the d.ilutezw 84 and ~.he connecting member 82 prior to moving the piston 8E~ improves tam at~i lity of the system to 6 accurately determine the aspirate a.nd dispense fluid volumes. If 7 the fluid path between d:iluter 84 and r_onru.ecting member 82 were 8 pressurized when the piston 86 began. to move the diluter 84 would 9 initially be forced. to overcome t:he press,arE built up in the fluid path. Thus, rather than aspirating fluid in response to movement 11 of piston 86, pressure in the f:Lxz~.d path between the dilut:er 84 and 12 sample probe 102 would be equalized with the pressure in the 13 di:Luter, otherwise it: is relat:ive:Ly difficult to precisely 14 determine the amount of fluid which was drawn in by the diluter 84.
However, by opening and then closin~.~ the bleed valve 78 the 16 pressure in the fluid line is set to atmospr~eric pressure. Thus, 17 florid can be immediately drawn into the sample probe tip 108 in 18 response to operation of the dilutes 84.
19 The apparatus also de tests leaks i.n t ~ze f laid paths . To detect leaks, the sample probe tip 108 is completely occluded and the 21 tubing is pressurized by t.urn.ing on the pump 70. The probe tip 108 22 is occluded and the pump 70 is left on. rC'rne pressure in the fluid 23 path between sample probe 102 and connec~.ting member 82 is thus 24 allowed to rise to a predetermined lim~~.t established during a calibration routine. ?~f no leaks exist, then the pressure will 26 rise to substantially the same cMalibrati.on level each time the 1. 4 WliINCiAK'I'GN. S<'.HUK(iIIV.
CiAC7N6AIN cF HAYU.S
'I'f:f: (6171 542-~=a0 FAX f617) 451-0913 1 sample probe is occluded. If a 1_eak exist:;, however, the pressure 2 will not rise to substantially t:.he same _eve.~ each time.
3 For each system a ca.Libra.tion rc~~.it=i.ne will be performed 4 whereby the tip is occluded and the pressure:, to which fluid in the fluid paths rise is determined.. T:rbe tip 108a may be occluded, for 6 example, by placing a calibration t:ip onto the sample probe body 7 106. Such a calibration tip would be providkad having an opening in 8 one end thereof to be attached to the sample probe port 106b and no 9 opening in the secand end thereaf.
The system controller X34 wauld them perform a sample probe 11 calibration routine to estab~~isYx a th.restxald pressure and voltage.
12 Referring now to FIG. 3, detector ;:i~cuit 112 is shown to 13 include a fluid pressure transducer 1'~?2 (corresponding to 14 transducer 98 and 22) having a pair of flui<:i ports 122a, 122b and a pair of electrical signal terminals 122c, 122d on which a 16 differential electrical signal is coupled to an amplification 17 circuit 124. The transducer 122 detects pressure changes which 18 result in the fluid path due to the occurrence of particular 19 events. For example, the transducer 122 senses pressure changes which result from a number of events including, but not limited to 21 some or all of the following: (a) fluid :1.(=_aks in a fluid path; (b) 22 contact between a sample probe ti.p and a surface of a fluid; (c) 23 aspiration of air r_hrough a sample probe; (d) obstruction of a 24 sample probe tip; anal (e) attachment. a.nd c3~atachment of. a sample tip to a sample probe.
26 In response to each o.f these events, the flow through pressure _ -t 5 ..
WF:INGAR'P1:N, 1('HUR(:IN, <~AI:NI:RIN 5i HAYS
'1'1a. (fil7> Sa_-32W
FAX (617) 4<Ill:l:

1 transducer 122 provides a corresponding differential voltage signal 2 to an amplifier circuit 124 at input terminals 124a, 124b. The 3 amplifier circuit 1.24 receives the different- ial signal fed thereto 4 from the pressure t:ransducer~ 122 and prc».r:ides am amplified single ended output signal a.t an otit:.put:. terrra_rzal 124c thereof. The 6 amplified output signal is fed to an input terminal 126a of a 7 signal conditioner and pump control circ~zit 126.
8 A plurality of event detector circuits 128-136 are coupled to 9 an output terminal 126b of the s:i.gnal. con~3ationer and pump control circuit 126 to receive a pressure signal. and a pump servo integrity 11 circuit 128 is coupled to an output t:erm:inal 126c of signal 12 conditioner and pump control circuit 126. While each of the 13 circuits 128-136 will be described .f_urthe~: b~,~low in general each of 14 th(=_ circuits 128-138 receives <zrr :i_n~:mt signal from signal conditioner and pump control c~irctrit: ~:?:6 at respective input 16 terminals 128a-136a thereof and compares tr~.e signal level of the 17 input signal to one or morel threshold ~:ignal. levels internally 18 generated. Each of_ the ciraui..ts 128-138 may be provided having 19 dii:ferent threshold signal levels. ~'ircuis~ 12~ may be software implemented or otherwise as may be effective 21 In response to the input signal having a signal level either 22 greater or less than the threshold signal levels, each of the 23 circuits 128-138 provide rt~presentativ~:~ o~at.put signals at the 24 output terminal thereof. Each of r_.he output: terminals 1:?8b -138b are: coupled to controller 94 described ak:~ove in conjunction with 26 FIG. 2.
- 1. F, _ W1~;INCiAR'1'liN. S('HtJH(71N.
(:ACiNEBIN k HAYL?S
'1'E.l, (61'n 542_2~~
PAX (6I'n 451-0313 1 The output signals indi.cat.E= wlnet:her or not a particular event 2 occurred or the status of the asp~.rate dispense apparatus. It 3 should be noted th<~t each o~ t. he circuits 1.28-138 and 126 may be 4 implemented via a programmed microprocessor(or: alternatively may be implemented via comparator circuits.
6 An output terminal 1264 of the signal conditioner and pump 7 control circuit 126 is coupled to an air p~.imp 140 corresponds to 8 pump 70.
9 The leak detector circuit 128 receivEa t:he signal on line 126b and detects whether any leaks exist iz~ tY~.e fluid paths of the 11 apparatus (FIG. 2) . When ofaerating in a l~:>ak detection mode the 12 controller 94 (FIG. 2) pz:~essux°izes the fluid paths in the 13 apparatus. Leak detector cix:coif 128 measux°es the signal level of 14 the signal on line 126b and in response to the signal level detector circuit 128 provides a signal to controller 94. The 16 signal level of the line 128b signal indicates to controller 94 17 whether or not a leak exists in r_he fluid paths of apparatus 66.
18 Fluid level detector circuit 130 detects when the distal end 19 108a of the sample probe r_ip 108 physically contacts and is inserted into a sample fluid.
21 Aspirate integrity detect circuit 132 detects whether or not 22 pump valve 80 is operating correctly, After a tip is placed on 23 the sample probe, the sample probe part 8C~b c:af pump valve 80 (FIG.
24 2) is closed and air is aspirated. "This should result in a pressure change to a predetermined level... If there is a leak in 26 the tubing or the sample probe part 80b did not close, then the ._ Wf:INGARTEN. S('HUItGIN.
GAC)NFBIN 3c HAYhS
TI;L. (61~ 54?-2-H(1 FA?i (6171 451-1)313 1 pressure change will not reach the propex° level. Thus the aspirate 2 integrity detect circuit 132 indicates whether or not the pump 3 valve 80 has worked correctly.
4 Clot detector circuit X34 detects whether or not the sample probe tip 108 was occluded durirx~~ asp:i.rate a.rtd dispense operations.
6 In those applications where probe t:ip 108 :i;;provided as a plastic 7 disposable probe tip, tip detector cirmxit 136 detects when the 8 probe tip is coupled to and decoupled from the sample probe body 9 106 based on a change in pressure to predetermined levels in each case.
11 Pump servo integrity circuit. 138 morl.i.t;ors the voltage signal 12 used to servo the .air pump 140 and dete:r°mz.nes whether or not an 13 appropriate servo voltage i:~ be:ing appa._i.ed t.a the pump 140. An 14 incorrect voltage would indicate an errc.>~~ i.r~ condition such as a blocked flow path.
16 By examining detector signals provided from detector circuits 17 128-138, a number of failures in the aspirate and dispense 18 apparatus of FIG. 2 can be detected. Foi: example, a failed 19 pressure transducer, a failed a.lr~ pump o~.~ a bleed valve stuck in the open position (i.e. always bleeda.u:~g) may be detected by 21 examining signals on lines 130b, 1:~6b and 1~~8b. A bleed valve 22 stuck in the closed position (i.e. never bleeding) may be detected 23 by examining the line 130b signal.
24 Similarly, the 132b signal may be examined to detect i.f the sample probe port of the pump valve i.s stl,~ck: in the open position 26 so as to continuously provide a~c f:r_c>m tl-iF aa.r° pump 70 (FIG.
2) to L 8 _.
wclNank rlcN, scHUltcl v.
(:AONEBIN .f. HAYI:B
'1'h;1, (6171 542 ~?~0 1~AX (617) 451-Oalz 1 the sample probe 102. A pump valve st.uc:k in the closed position 2 such that the pump valve fails t:o providr~ ai:r. tca the sample probe 3 102 may be detected by examining the 13c)t~ a.:nci 138b signals.
4 A leak in the tubin~~ large enoagr~ to affect dispense performance or the level .sense operation may be det:ected by 6 examining the line 138b, 132b anal 128b sagna~s.
7 It should be noted that: each of. the event detector circuits 8 128-138 compares the respective input;. signal fed thereto to 9 internally generated threshold voltage levels to determine the occurrence or non-occurrence of pax~ti.c:ular eve=nt5. In response to 11 the compare operations, each of the event c~.et.ector circuits 128-138 12 provides an appropriate. output signal to controller 94.
13 Referring now to F'TG. 4, the details of the signal conditioner 14 and pump control circuit 126 are shown.
The input to the signal conditioner and pump control circuit 16 is coupled through a resistor 155 to an ~...nverting input of an 17 inverting amplifier 160. The inverting amplifier 160 provides the 18 line 126b signal to the detectors 128-136.
19 A resistor R1 and capacitor C~1 ar(~ coupled in a negative feed-back path as shown between the oi.ztput terminal of the 21 inverting amplifier 160 and the inverting input terminal of the 22 amplifier 160. A non-inverting input of the inverting amplifier 23 160 is coupled to a first termpnal 162, ~~f a sample and hold 24 circuit 162.
A charge storing capal~.it:c>:r 1.~4 fnr r:he hold function is 26 coupled between a second term:i.nal 162b of t:he sample and hold _ 1g Wl:INCARTl:N, SY'HURlUIN, GA(~NE81N & HAYBS
TGI.(617) 54~ .390 I~AX (617) 451-031 1 circuit 162 and ground. A third terminal 162c of the sample and 2 hold circuit 162 is coupled to an output terminal of a second 3 inverting amplifier 166 and a f oux°th te.rmioual. 162a of the sample 4 and hold circuit 162 is coupled too the s~~~tem controller 94.
The non-inverting input of:' ~..he seconc:l znvert:ing amplifier 165 6 is coupled to ground arnd the irme.rting :i.r:c~:~u~. of the amplifier 165 7 is coupled through a resistor R.2 to ttr~~ coutput:. terminal of the 8 first inverting amplifier 160, A f_eedbaci~ capacitor C2 is coupled 9 between the output and the invext.ing :input: ~;:W th.e amplifier 166.
The output terminal 160c of the firat amplifier 160 is also 11 coupled through a resistor R3 to an in~rerting input of a third 12 inverting amplifier 170. The non-inverti,rlg i.nput:. of the inverting 13 amplifier 170 is coupled to a reference voltage 171 through a 14 voltage divider network 172 having resisto.>~s R4, R5 selected in conjunction with the voltage lavel of true reference voltage 171 16 such that a predetermined threshold voltage is provided to the non-17 inverting input terminal 170b of the inverting amplifier 170.
18 A capacitor C3 is coupled between th~c output terminal and 19 inverting input of amplifier 170.
The output terminal 170=v clf the thi:coi inverting amplifier 170 21 is coupled to a first terminal 174a of a sample and hold circuit 22 174. A charging capacitor 1'76 ~.s c~orar~ecte.d between a second 23 terminal 174b of the sample and hold ci.:rcu:i.t 174 and ground. A
24 third terminal 174c of the samp:Le a.nd ho.l.~3 c:~ircuit 174 is coupled through a resistor R6 to an ir~~>ut termin<~~.1 178c of a voltage 26 regwlator circuit 1'.78 and a faurtr~ t::erminaZ ~f.74d of the s<~mple and W) -Wf:IN<:AK'PEN, SC'HUKOIN.
<:At.iNIBIN & HAYF'.,S
rH:l., (em so? ~:vo FA7i (61'>) aSlflili 1 hold circuit 174 is c:ouplec~ t:c~ the sy~;t.erri cor:~troller 94. The 2 system controller provides a cc>ntrol si.g-r~al to tine sample and hold 3 circuit causing it to operate zn either a samp:Le mode or a hold 4 mode.
The voltage regulator 178 has a voltage input terminal 178a 6 coupled to a refe:renc:e voltage source 17~~ . A voltage output 7 terminal 178b of regu7.ator 178 ~ s c;oup:l.ed through a resistor to 8 control pump 140. A zener diode 184 i.s <:~raupled between the input 9 178c and ground clamping the input to not exceed a predetermined voltage.
11 A resistor 186 is coupled between ric~de 180 and the anode of 12 the' zener diode 189: as shown. A switch L~,~<:is coupled :between a 13 second terminal of pump 140 ( cr_:frx°espomd:~.ng to air pump 70 ) and 14 ground. In response to a fi__rst c:o:r~trol aigr~al from controller 94 the switch 192 is made condu.rti_ng, activating the air pump 140.
16 The sample and hold circuit 162 establishes a reference or 17 normalized voltage level for the signal orl 1_ine 126b corresponding 18 to a reference or normali~,ed pressure lcwel in the pressure 19 transducer 122.
The sample and hold circuit 162 is L:~laced a-n sample mode by 21 the controller 94 in which it cJonnects a signal path between the 22 output of amplifier 166 and the non-invex:°ting input of amplifier 23 16C . Amplifier 166 provides am output s~.gna~. to sample and hold 24 input terminal 162c.
Amplifier 166 provides a bias signa.L at its output that is 26 applied to the non-inverting input of ampl.if:~_er 160 via sample and WfT.IMOAR'f'EN, SCHUR(iIIV, 'flil. (617) S4?-'2:'.90 1~AX (617) 4.5111313 1 hold circuit 162 until the signal pravided at the output of 2 amplifier 160 is driven to a voltage lever. ca~rresponding t:o ground.
3 At this point controller 94 4 provides a second control signal tc7 sa.mpl.e and hold terminal 162d which places the sample and held circuit: in the hold mode. The 6 voltage level of the sample axed hold ca.rc~zit is thus setting a 7 va:Lue which causes the line 126b output to be zero for what ever 8 pressure is sensed. 'Thereafter the voltage level of the signal on 9 line 126b is representative of relative pressure changes detected by the pressure transducer.
11 System operation:
12 (1) a system cycle begins witYx the sample probe 102 (FIG. 2) 13 wit:bout a tip. A control signal. from t~n:~ cv~ontroller 94 (FIG. 2) 14 biases the switch 192 into its non conduct:~~on state thus decoupling the air pump 140 from ground and thereby turning off the air pump 16 140. With air pump 140 off, no pressure exists in the fluid path 17 in which the flow through pressure transducer 122 is disposed.
18 Thus, the pressure transducer 122 provides a differential output 19 signal corresponding to zero pressui.°e t.o the input: terminals of the amplifier 124 (FIG. 3) . Also w~.th the pum~,a 140 turned off, the 21 voltage regulator 1'78 and zer~er c:3:i.ode 184 zv~i:ntain the voltage at 22 line 178b at a set voltage lez~el.. Fi,zrthex°rr~orf~, the output terminal 23 of amplifier 170 provides a voltage level. c~orrespanding to the rail 24 voltage.
(2) The controller 94 then provides a control signal to the 26 sample and hold circuit 1F~2. zn response to the control signal, _ ~ 2 ._ WE1NGAR'PGN. 1('HIJRGIN.
(,1A(iNG;HIN & HAYI~;S
'fla_ (617) ~~1~_-~°VO
1'A\ (6171 9sla)~13 1 the sample and hold circuit 162 drives c~~atvput. 126b to zero 'volts.
2 (3) The controller 94 here provides a control signal to turn 3 th? pump valve 80 on (FIG. 2) and also px:ovides a second control 4 signal to bias the switch 192 into it.s ~oxrduction state thereby turning on the air pump. When the pump is initially turned on the 6 vo:Ltage across the pump is <~t a high vol.ta.ge. When pump 140 is 7 first turned on amplifier 170 servas the pump voltage so that line 8 12 Gb is at the vol tape at i is nonirmerti rig input . Prior to the 9 pump turn-on, the output ofamplifier :i_s at the positive rail driving current through resistor 1'7C and fog:°cing line 178c to the 11 zener voltage set by zener 184. This canrses a rapid spinning of 12 pump 140 . Over time, amplif. ier 1 a0 ser~~c:~s the loop resulting in 13 its output falling as line 1~6b i..nc.rease, wi;~h th.e build up of the 14 pressure signal from transducer 122. At a desired pressure voltage, the sample and hold circuit 174 i5 caused by controller 94 16 to hold that voltage far a cycle, Also, in response to the pump 17 being turned on the pressure in tyre system fluid lines rises 18 rapidly.
19 (4) After a period c;f typicall.y 5~:)0 milli-seconds the controller 94 provides a control_ signal on li:r~e 176d to the control 21 poet of the second sample axed hold c:~:i.rcr,~~ t x..74 thus placing the 22 sample and hold circuit. in the hc~lc:3 mode. The zeroing of output 23 line 126b procedure of step "2" is repeated here as a very fast 24 recalibration step.

(5) The controller 94 then measures the output of the 26 integrity circuit 138 to determine if the signal is within a _ 2 3 ..
W1?INC3AH'1'I:N. SC'HIJR(ilN.
GAGNEBIN & HAYFS
'1'6L (61'>l 542W90 UAa (619) 4.!I-031:i 1 predetermined voltage range. If the signal has a voltage level 2 outside a predetermined voltage range ::hen an error signal is 3 generated by the controller G4 and processing stops. If the signal 4 has a voltage level within a predeterminf=.d vcaltage r<~nge then processing continues and the cant::rc)lle:r mcwr:~s the sample probe 102 6 via robot arm 23 to a station 25 (5'IG. 1.? ar which it may pick up 7 a disposable probe tip.

8 (6) Line 126b is again zeroed as in step "2" and a fresh tip 9 is placed on the probe . Du rind p:Lac:emerut: of a probe t:ip on the probe body, the air in the line ex:perierr~:;e5 a brief t.:ransient as 11 the tip is inserted. Controller 94 examines the signal on line 12 136b from detector 136 to determ:irre whethE~r the signal corresponds 13 to a preset level for a predetermined periled of time to confirm tip 14 placement . The pump falter :is oc~ and a.l:i w<-dues stay as set .
(7) The controller 94 turns aff. tha pump valve 80. The air 16 pump 140 remains running.
17 (8) Line 126b is zeroed again accordirig to step "2"
18 (9) Once the tip is coupled try the sample probe body, the 19 controller 94 engages the stepper rnot:or 92 which draws the piston 86 into the cylinder 84. Since r_he tip has not yet been disposed 21 in a fluid, this results in air being asp:~.rated into the fluid 22 paths through the disposable sample ~ rot~c~ tip. A:Eter the 23 as~~iration is complete, the cant~rr_ol:Le:e determines whether an error 24 exists via the aspirate integrity detectar c:a_rcuit 130 (FIG. 3) as follows 26 (10) The controller 94 turns true pump valve 80 on thus .. 2 4 ..
WFIN(iAKI'GN. SY'.HUR(.IN, (7A<~Nf:RIN & HAYF~,S
'1'I:1. (617) 54=-290 FAX (617) 451m1z 1 supplying air flow to the sample L~robe 10;~~ . The controller 94 then 2 zeros line 126b .
3 ( 11 ) The controller 94 moves tYie samy:l.e probe via robot arm 23 4 to a position in which the samp:Lh~ px~obE: c:4a.x~ <:gccess a sample tube holding a fluid sample.
6 (12) The sample probe is lowered in tmhe direction of the fluid 7 tube 27. Once the disposable probe tip reaches the fluid, the 8 prE~ssure transducer 122 senses a change izn pressure and provides a 9 signal to the detector circ~zit 112. Ire response to the signal provided thereto from the pressure trarm;d~cer 122, the detector 11 circuit 130 generates a signal ors output .30b and provides the 12 signal to the controller.
13 (13) While monitoring line 130b, the cc~n.troller 94 moves the 14 disposable tip into the fluid sample to a. predetermined penetration depth selected to allow aspiration of the needed fluid.
16 (14) After the disposable tip is moved to the predetermined 17 depth, the controller waits for a predetermined period of time, 18 typically about 500 msec, and then examines the signal on line 128b 19 provided by leak detect circuit 128 (FZCa" 3> to determine if any leaks are present in the system.
21 ( 15 ) The controller 94 provides .ront~-o1 signals to turn on the 22 bleed valve and turn off the a.ir pump a~ described above to 23 normalize the fluid line in preparation f.or aspirating fluid.
24 (16) The controller 95 then turns off the pump valve 80 and ( 17 ) engages the stepper motor 92 ( F:~(s . 3 ) causing the diluter 26 to aspirate fluid into the sample probe tip 108. The controller 94 _ ~~ r";
WF:INtiAk'1'IiN, SC'HUkt~iN, (~ACNFHIN & HAYF;S
'TEI_ (617) 542-329(1 F'AX (617) 4SIa1'i13 1 also monitors the lira.e 1_34b signal pc~~:w~.ded by clot detector 2 circuit 134 to determine if the sample probe fluid path has been 3 obstructed during the aspirate operation.
4 (18) If no clot detection occurs then the controller 94 moves the sample probe to a position in which a sample fluid may be 6 dispensed into a cuvette 32.
7 (19) The controller 94 provides a corztral signal causing the 8 stepper motor to dispense the sample fluid into the cuvette 32.
9 ThE=_ controller again examine s the .line 1..'3~Eb s:Lgnal to determine if the sample probe fluid path has been obstr-~zct.ed during the dispense 11 operation.
12 (20) After the dispense aperat:.ion is c,:amplete the controller 13 94 moves the probe body to eject the disposable tip. The signal on 14 line 136b provided by tip detector circuit '~36 (FIG. 3) should be present a few msec. thereby :inda_cat:ing that t:he disposable tip is 16 removed from the sample probe body.
17 A leak is detected by leak det:ec:t:ion c rcuit 128 (F:ig. 3) in 18 the following manner. As described above ~n conjunction with FIG.
19 4, the disposable tip of the sample probe -1s moved toward the fluid sample with the air pump on thus allowimg the detection of the 21 fluid sample level. Once the disposable t.i.p is disposed in the 22 fluid, the air pump remains oii thereby letting pressure build up in 23 the fluid lines.
24 The air pump provides the ai.r at a flaw rate which does not allow the pressure t;o rise to a level which causes a bubb_Le in the 26 sample fluid. Rather, pressure in the sampl~:r probe and fluid path _ 2~; ..
WEINGARTf:N, SCHURCIN, C7A(:NEHIN & HAYPS
'1'1I. (617) .54:-x'90 PAX (617) 4$I-11313 1 leading thereto builds to a static pressure. The pressure range of 2 the static pressure will be known from a calibration step to be 3 described below.
4 The predetermined static pressure level corresponds to an equalizing pressure. Ideally the pressure should build up to the 6 same value each time although ir:a prarti~c.e it is recognized that 7 this will not be the case. However, if a kmale or fluid leak exists 8 in the fluid path then the pressure wall not rise to the 9 predetermined level and thus the line 12~b signal will not reach a comparison threshold voltage levF~~. E~stabl.ished in. circuit 128. The 11 circuit 128 will thus provide an output ~ig~>.al on line 128b which 12 indicates that the threshold has not been reached and that a leak 13 exists in the fluid path.
14 The static pressure and tYws the thr°eskuold needed i:n circuit 128 will not be the same for every inst runr~ent . Rather it is a 16 function of the tubing length, tubing diameters, and mechanical 17 tolerances of each of the ;system compormnts, etc.... Thus, a 18 calibration step is used t.o :yet the thx:PSho:~.d.
19 To cal ibrate the system, steps 1 - 5 a r_ a repeated as above . The sample probe is completely occluded such as by placing a 21 calibration tip having a closed end ora tire probe body. This 22 establishes a calibration voa..tagf=~ foz: th,a cc::dmpar:ison thrE~shold of 23 circuit 128. The actual threshold voltage in circuit 128 is set a 24 small voltage below that to insure that t:he voltage on line 126b exceeds the threshold where leaks are nc>C present and the output 26 128b changes to reflect. that.
WF:INGAN'f'I~i,N. SCHUR(iIN, (iA(:NIiBIN & HAYIi;S
'l'L;L (617) 54v 229(1 1~AX (617) 451-0'ilz 1 The level sense detect ci-:r~~c:ui t~ 130 c E~spands to the line 126b 2 signal and compares it to an iezternal reference. The output on 3 line 130b is high until the disposable tip contacts a sample fluid.
4 Then, with the air pump continuing to provide an air flow resulting in the pressure transducer 122 causing a si~~nal rise on line 126b 6 above the threshold voltage t,txe signal are :~:irre 13()b drops typically 7 to about zero volts, thus incticat::i.xlg that physical r_antact between 8 the sample probe anal the sample fluid has occurred.
9 The aspirate integrity circuit 132 receives the signal on line 126b and if it is below a threshold voltage level established 11 internally provides an output signal an l..ime 132b having a high 12 vo-1 tage (typically 5 volts) ,. t:)nce the s:Lgrva:l li~vel on :line 126b 13 reaches the threshold voltage, true (vi.r.c~b:i..t~ 7_32b provicie;3 on line 14 182 b a low voltage (typically a~ero) .
During an aspiration operation, the vent port of the pump 16 valve is opened and the sample probe part of the pump valve should 17 be closed to thus isolate the bleed valvE~, the coil and air pump 18 from the diluter and pressure transducer. However, it is not 19 possible to determine whether the pump v~:a:Lve operated correctly.
Thus with the sample probe pc5r~: of the pi.~mp value closed, air is 21 aspirated through the sample probe. This should result in a 22 pressure change in the fluid path in which the transducer is 23 disposed.
24 If a leak exists in the pump valve, Enowever, the pressure generated due to the aspirate opFrat.ion w:i.:~l ascot xise to the proper 26 threshold level for circuit. 132. C'c.~x~se~:~uent.ly the pressure WI;IN(:AR'1'L;N, SC'HIJRCIIN, GACiNEBIN & HAYFS
'PHI. (617) 542-2290 FAX (617) 451-0313 1 transducer 122 would provide a signal having an amplitude 2 insufficient to reach the threshold vo:Lta.ge~ The circuit: 132 thus 3 provides at the output. terminal 132b a signal having a voltage 4 level indicating that a leak in the pump valve was detected during an aspirate operation.
6 The clot detection circuit: 134 has a dual.. comparison. function 7 with a pair of threshold levels set to detel~t whether the voltage 8 level of the signal c>n line 12F>b fal.l~; w::it.hira. a predetermined 9 voltage range between them, This ~.~ because the pressure transducer 122 (FIG. 3) measures different pressure levels during 11 aspirate and dispense operations. For e:,~ample, when this diluter 12 piston stops after being mowed during ara. a~ap:irate operation, the 13 pressure measured by the transducer should drop below a 14 prE=_determined threshold voltage. L:~ the Llressure transducer fails to indicate such a pressure drop then the ~rolt~ge level of the line 16 12E>b signal would likewise not: change, thus indicating that the 17 sample probe tip was occluded.
18 Similarly, during a dispense operat:i.on the pressure should 19 stay above a predetermined threshold voltage. If the pressure transducer senses a pressur.~e drop or' ripe during a dispense 21 operation, then the voltage level of the l:Lne 1.26b signal would 22 likewise change to a level outside the predetermined threshold 23 voltage range thus indicating trrat. the: sample probe tip was 24 occluded during the dispense operation.
The clot detection circuit may also be of the type described 26 in co-pending patent applicat ion serial ____~ ~ number filed .j ca Wf~:IN(iAR'I~I:N, Sl.'HIIfL(:IN.
(:A<:NT:BIN X HAYES
TI:1. f617) Sa? ~?411 f~AX (61~ 451J1713 1 (CCD-192XX - V07JLTME DETECT I:C,;'N APPARATUS AND METHOD) 2 assigned to the assignee of the present izivention and incorporated 3 herein by reference 4 The pump servo integrity circuit 138 with input terminal is coupled to an output terminal, line 126,:, ~~)f the sample and hold 6 circuit 174 (FIG. 4) . :If this air pump serve: voltage signal is not.
7 within a predetermined range, then the pump servo integrity circuit 8 138 provides an output signal so indicatiing ate output terminal 9 138b. This signal is only examined by the controller 94 when setting the pump voltage.
11 Two threshold voltages are provided in circuit 138 12 respectively set at opposite voltage f:~xt~remes. The threshold 13 voltage levels are selected such. that if t:~e l..ine 126c signal level 14 exceeds these threshold levels, it indicates that the pump control circuit is unable to servo the pump iru t::Yne desired manner. Thus 16 when the line 126c signal is between these thresholds, the line 17 138c output voltage level is h~c~Yi. Wherz the :Lizie 126c Signal is 18 outside the threshoa_d voltage range the oz.zrp~zt signal is about zero 19 volts.
It should be noted, txnat in some embodiments, it may be 21 preferable to detect the signal level of the line 126b signal 22 rather than the line 126c signal i.n w2~~i.ctn case the i~hreshold 23 voltage levels would be set differently.
24 The tip detection circuit 13h has a ~~a.i.r of threshold levels set internally at +/- 1. ow voltages defini.r_q <~ range about zero for 26 the line 126b signal level above which t~Lie Line 12~b signal goes WI;1N(:AHTGN, SC'HUHC71N.
(IA(.lNf~:RIN & HAYES
'1'1;l., (61'7) 542-23N0 1'Ah (61'n a5I-0z13 1 upon tip installation and below whicY~. lzne 126b goes an tip 2 removal.
3 Inside this range, the output 136b :i.~ rai.gh; outside the range 4 tha output is low.
When a disposable samp:Le t ip is p:1<.~ced on the sample probe 6 body, the voltage leve3. of the la..ne 1.26b ~~ignal will. rapidly rise.
7 The controller 94 examines the signal level of line 136b at the 8 output terminal of the tip detection ci.rv,.:ua t . The cant roller 94 9 detects the signal level of t: he line l3Fib si.~~nal and verifies that the signal remains high for a predetermined time period, typically 11 about 10 msec. Then there exists a re:L;~ta vely high probability 12 that a tip was in the ti.p r~olde~:~ arid t:r,at ~~ disposable tip was 13 actually placed onto the probe body.
14 In a similar manner, when ~:~ Iaispc~asabl~~ t: ip is removed from the probe body, a pressuz°e changed~ oc:curs :end is detected by the 16 pressure transducer. The pressure transducer provides a 17 cox-responding output signal having a volt:age transient below the 18 range which is detect=ed. In the everzt: that a tip is nat removed, 19 the controller 94 detects the line 136b s.i.gnal staying in range and acts to prevent a new tip from bt.=_ing dispcseci over an old tip that 21 way; not removed.
22 Having shown the preferred embodiment, those skilled in the 23 art. will realize many variat~_ons ax°e possib:~.e which will still be 24 within the scope and spirit ~7f the claimet3 invention. Therefore, it is the intention to limit t:he invention only as indicated by the 26 scope of the claims.

WI~;INtiAH'I'I~;N. 1<'HUNGIN.
(:A(7NFRIN & HAYFS
rla.tFl7> sa= ~_=w~
rAx c6m a;i ~zn

Claims (23)

1. An apparatus far aspirating and dispensing a sample fluid comprises:
a constant air source having an output port;
a pump valve having a first port coupled to the output port of said constant air source, having a sample probe port and having a vent port;
a connecting member having a first port coupled to the sample probe port of said pump valve, having a second port and having a third port;
a diluter having an output port coupled to the second port of said connecting member;
a flow through pressure transducer having a first port coupled to the third port of said connecting element and having a second port to provide a pressure signal; and a sample probe having a first port coupled to the second port of said flow through pressure transducer; and a controller for said air source, pump valve, diluters and sample probe operating as a function of said pressure signal.

2. The apparatus of Claim 1 further comprising a bleed valve hawing a first port coupled to the output port of said constant air source and having a second port coupled to the first port of said pump valve and controlled vent.

3. The apparatus of Claim 2 further comprising an accumulator having a first port coupled to the output port of said air pump an output port coupled to the input port of said bleed valve.

4. The apparatus of Claim 3 further comprising a connector having a first port coupled to the output port of said constant air source, a second port coupled to the input port of said accumulator and output port coupled to a vent tube.

5. The apparatus of Claim 4 wherein said flow through pressure transducer provides said pressure signal on a pair of electrical output terminals and in response to pressure changes in a fluid path between said sample probe and said connector element said flow through pressure transducer provides a differential output signal at the pair of electrical output terminals.

6. The apparatus of Claim 1 wherein said controller comprises a microprocessor.

7. The apparatus of Claim 1 further comprising a detector circuit coupled to said pressure signal from said flow through pressure transducer to signal to said controller a plurality of conditions reflected by the pressure in said transducer.

8. The apparatus of Claim 7 wherein said detector circuit comprises :
an amplifier circuit having a first terminal coupled to said flow through pressure transducer and having a second terminal;
a signal conditioning circuit having a first terminal coupled to the output terminal of said amplifier circuit and having a second terminal coupled to at least one of:
(a) a leak detector circuit;
(b) a fluid level detector circuit;
(c) an aspirate integrity circuit;
(d) a clot detection circuit;
(e) a tip detector circuit; and (f) pump servo integrity each of which has a nominal state signal set therein by said signal level conditioning circuit under operation of said controller.

9. The apparatus of Claim 8 wherein said signal conditioning circuit comprises:
a first inverting amplifier having a negative input terminal coupled to the first terminal of said signal conditioning circuit, having a positive input terminal and having an output terminal;
a second inverting amplifier having a negative input terminal coupled to the output terminal of said first inverting amplifier having a positive input terminal coupled to ground and having an output terminal;

a sample and hold circuit having an input terminal coupled to the output terminal of said second inverting amplifier, having an output terminal coupled to the positive output terminal of said first inverting amplifier and having a control terminal; and said controller coupled to the control terminal of said sample and hold circuit.

10. An apparatus for aspirating and dispensing a sample fluid comprising:
a constant air source having an output port;
a bleed valve having a first port coupled to the output port of said constant air source and having a second port;
a pump valve having a first port coupled to the output port of said bleed valve, having a sample probe port and having a vent port;
a connecting member having a first port coupled to the sample probe port of said pump valve, having a second port and having a third port;
a diluter having an output port coupled t o the second port of said connecting member;
a flow through pressure transducer having a first port coupled to the third port of said connecting element and having a second port to provide a pressure signal;
a sample probe having a first port coupled to the second port of said flow through pressure transducer; and a controller for said air source, bleed value, pump value, diluter and probe operating as a function of said pressure signal.

11. The apparatus of Claim 10 further comprising a detector circuit coupled to said flow through pressure transducer.

12. The apparatus of Claim 11 wherein said detector circuit comprises:
an amplifier circuit having a first terminal coupled to said flow through pressure transducer and having a second terminal;
a signal conditioning circuit having a first terminal coupled to the output terminal of said amplifier circuit and having a second terminal coupled to at least one of:
(a) a leak detector circuit;
(b) a fluid level detector circuit;
(c) an aspirate integrity circuit;
(d) a clot detection circuit; and (e) a tip detector circuit; and (f) a pump servo integrity circuit each of which has a nominal state signal level set therein by said signal conditioning circuit under operation of said controller.

13. The apparatus of Claim 12 wherein said signal conditioning circuit comprises:
a first inverting amplifier having a negative input terminal coupled to the first terminal of said signal conditioning circuit, having a positive input terminal and having an output terminal;
a second inverting amplifier having a negative input terminal coupled to the output. terminal of said first inverting amplifier hawing a positive input terminal coupled to ground and having an output terminal;
a sample and hold circuit having an input terminal coupled to the output terminal of said second inverting amplifier, having an output terminal coupled to the positive input terminal of said first inverting amplifier and having a control terminal; and said controller coupled to the control terminal of said sample and hold circuit.

14. A method for determining the occurrence of physical contact between a probe and a surface of a liquid comprising the steps of:
(a) establishing a normalized pressure representing voltage corresponding to a zero pressure signal in a flow through pressure transducer;
(b) providing a constant air flow through the pressure transducer and a sample probe;
(c) moving the sample probe in a direction of a fluid;
(d) sensing a change in pressure in a fluid path inline with a flow through the pressure transducer; and (e) providing a transducer pressure signal representing the fluid contact in response to tree change in pressure in the fluid path.

15. The method of Claim 14 wherein the step of establishing a normalized pressure voltage comprises tree step of:
depressurizing a fluid path between an air source and a sample probe wherein the fluid path includes a flow through pressure transducer;
providing a first signal having a first voltage level to a first input terminal of an inverting amplifier coupled to the flow through pressure transducer;
driving an output signal of the inverting amplifier to a reference voltage representative of an existing pressure level in the flow through pressure transducer;
sampling, in a sample and hold circuit, the predetermined reference voltage at the output terminal of the amplifier;
placing the sample and hold circuit in a hold mode to maintains a threshold voltage at a second terminal of the amplifier circuit.

16. A method of detecting leaks in a fluid path of an aspirate and dispense apparatus includes the steps of:
engaging a constant air source to pressurize a fluid path having an inline flow through pressure transducer disposed between the constant air source and a sample probe;
occluding the sample probe; and comparing a signal provided by the pressure transducer with the probe occluded to a threshold signal.

17. The method of Claim 16 wherein the step of occluding the sample probe includes the step of inserting the sample probe into a sample fluid.

18. The method of Claim 17 wherein after the step of inserting the sample probe into the sample fluid the method further comprises the step of comparing a signal provided by the flow through pressure transducer to a threshold signal.

19. A method of verifying aspirate integrity of an aspirate and dispense apparatus including the steps of:
engaging an inline flow through pressure transducer disposed between an air source and a dilutes on one hand and a sample probe on the other hand when the fluid path is in an aspirate mode which isolates the air source from the diluter by a valve;
comparing an output from the pressure transducer during aspiration to a reference to determine the integrity of the valve.

20. A method of detecting the occurrence of a clot in an aspirate and dispense apparatus including the steps of:
engaging an inline flow through pressure transducer disposed between a diluter and a sample probe where the fluid path is in each of an aspirate and dispense mode;
comparing an output from the pressure transducer during aspiration and dispensing to respective references to determine the integrity of the fluid path.

21. A method of verifying tip placement and removal in an aspirate and dispense apparatus including the steps of:
engaging an air source to provide an air flow in a fluid path part an inline flow through pressure transducer disposed between the air source and a sample probe when the probe is receiving and removing a sample tip;
comparing an output from the pressure transducer during tip insertion and removal against respective references to determine the integrity of tip insertion and removal respectively.

22. A method of verifying pump integrity of an aspirate and dispense apparatus including the steps of:
engaging an air source with a servo circuit to provide an air flow in a fluid path past an inline flow through pressure transducer disposed between an air source and a diluter on one hand and a sample probe on the other hand where the air flow is to provide a desired pressure; and comparing a servo signal during engaging of the air source to respective references to determine whether the servo circuit is able to servo the air source.

23. The method of claims 16, 19, 20, 21, or 22 further including the step of establishing a normalized pressure and servo signal respectively for said comparing step.