throbber
United States Patent
`Hinman
`
`[191
`
`3,863,049
`1111
`1451 Jan. 28, 1975
`
`[54] TEMPERATURE CONTROL APPARATUS
`_
`ngsYggfmucAL TYPE CHEMISTRY
`A
`Inventor: Clyde D. Hinman, Wilton‘ Conn,
`[75]
`[73] Assignee: Union Carbide Corporation. New
`York. NY-
`[22]
`Filed:
`May 31 1972
`[21] Appl. No.: 258,259
`
`[52] US. Cl.................. .. 219/389, 165/39, 219/370,
`219/441, 219/494, 233/“
`Int. Cl. ......................... F27b 7/00, F27d 11/02
`[51]
`Field of Search ........." 219/370, 385, 388’ 389,
`[58]
`219/400, 413, 430’ 441, 494., 34/8, 58’ 59;
`165/39; 233/11
`
`[56]
`
`2,742,190
`
`References Cited
`UNITED STATES PATENTS
`6/1973 Glam ................................ .. 219/389
`
`2.768.546
`3,246,688
`3,322,338
`3,529,358
`3,566,070
`
`Shipes ................................. .. 165/39
`10/1973
`4/1966 Colburn .............................. 1. 165/39
`5/1967
`Stallman et al. ...................... 233/23
`9/1970
`Robinson ...................... .. 219/400 x
`2/1971
`Pesgzlt ............................. 219/388 X
`
`Primary Examiner—Volodymyr Y. Maycwsky
`Almrncy, Agent, or Firm—Frederick J. McCarthy
`
`1571
`
`ABSTRACT
`
`,
`.
`A temperature control apparatus for raising and con-
`trolling the temperature of small volumes of liquid by
`heating the liquid and detecting the instantaneous
`temperature and rate of temperature increase and uti-
`lizing this information to control the heating of the liq-
`uid so that the desired liquid temperature is attained
`and maintained in a minimum time interval.
`
`4 Claims, 5 Drawing Figures
`
`:t
`
`
`
`
`1
`54
`_
`\
`L A \\\
`
`2-":\ “\V|1_fllllt\\\\\\‘l
`""
`///'r
`
`-
`.
`//¢11I
`I11 /A\
`
`=7’W AW
`
`2.3 A%
`nun-.50
`xx I g 11%
`
`Ir‘Er—‘-
`-_=
`g I
`
`~
`~
`\ ’6/
`~
`,
`N
`\
`['0’
`
`
`i

`§ [51’
`s
`1:
`g .4112
`s
`1
`
`
`t,
`1!, KM W
`n
`
`- 1V/////)
`
`
`
`
`1\\ I
`
`z
`NI!”
`70 557065
`ElfifU/f lflfl
`
`
`
`i
`
`g:
`
`:
`i
`i
`i
`3
`:
`3
`
`
`
`Page 1 0f 10
`
`'
`
`Samsung Exhibit 1010
`
`
`
`Page 1 of 10
`
`Samsung Exhibit 1010
`
`

`

`PAIENIEUJMIQIS
`
`‘
`
`3.863 . 049
`
`SHEEI
`
`1 or
`
`'5
`
`
`\IIIIIA_'llllllllllnlllllll- I I
`
`
`
`
`
`‘
`
`:1;
`
`:3
`
`—
`
`
`
`
`‘Tlllllllffi-‘Vllfvza-Ti .
`
`
`
`
`II «Inn ‘|- m
`ill!!!“ ‘I_ l‘
`"'|>II_IIl_I
`illLll’Irlvll
`
`
`
`
`
`F§ '
`
`
`
`
`
`W 7059/065C/RCU/T/flfl
`
`
`
`
`‘ V N iu‘i'if-igiffi
`\
`
`
`v § sulnuwmln§
`
`
`
`
`
`
`‘Lii'
`-.
`l_IIu
`IIIt
`g
`
`
`‘6 ‘i'gl/I/Illigvzlfi;fl§
`wmi"
`H
`i
`
`r
`' v \V
`h
`Q
`
`
`
`
`
`
`E
`
` _ __ ; ‘\\\\\\\)}})_\_‘1 \V
`\fi
`
`
`V
`$53;
`
`
`/;
`smunmumlmwr§
`
`
`
`
`
`aA-.m-
`
`:'1'"III, &
`-..aJ r‘
`“\“““‘
`
`7///1’.’.’{‘...
`
`I:
`'
`V/Iili..,
`"nunnunlllln’lnln_"umII ’4
`u-u -
`
`
`
`
`
`
`r
`
`
`“
`
`1
`
`'¢
`
`nfl
`
`
`
`Page ‘2 of 10
`
`
`
`Page 2 of 10
`
`

`

`PATENIEDJANZBWS
`
`3.863.049
`
`'
`
`SHEET 20F 5
`
`
`
`
`
`Page 3 of 10
`
`
`
`Page 3 of 10
`
`

`

`PATENTED JAN 2 8 l975
`
`3.863.049
`
`SHEET 30F 5
`
`m
`
`
`
`9%,“sh%\\Smw_\\_
`
`IV-IIIJF+11|hIHHHIWIHIIHIHWIIIII.Illl..\l\...HHIIII|I|III
`
`
`
`
`wkxkvfii__QN.N_Wbeéxkzqu____.______~_____V.____3+___ll.‘\\|lz__x/__w0\\\\\l/./kxI_E_\_§\m\mwa,.\.5:3qu\.\JmLI!
` WkknD9k_________kxbbmxxuNmkxxxxuwkwk.._xmQmuuqkkéauREE
`
`
`
`
`A|WkQK
`
`symya'aawyx
`
`kakV‘QWQanxINh
`
`QWWCWNQ
`
`U0.kwu‘
`
`Page 4 of 10
`
`
`
`Page 4 of 10
`
`

`

`PATEN IED JAN 2 8 [915
`
`3.863.049
`
`SHEEI NF 5
`
`gvfifii
`
`RxMkv‘w,MKQ-QSI_
`
`QW\
`
`wabkxm
`
`WWWV§nx
`
`QWQWPKN
`
`k\§UQ\U
`
`
`
`
`
`WQVQkafiwxv‘Ill.
`
`Page 5~0f10
`
`
`
`Page 5 of 10
`
`
`
`
`

`

`PATENIEDJAnzams '
`
`3.863.049
`
`SHEET 5 OF 5
`
`
`
`hmm,
`
`_m_lqa_M:Vm
`
`_Ir.
`
`NVM:
`
`mNm.Nam.
`
`gm.
`
`Page 6 of 10
`
`
`
`Page 6 of 10
`
`
`
`
`
`

`

`1
`TEMPERATURE CONTROL APPARATUS FOR A
`CENTRIFUGAL-TYPE CHEMISTRY ANALYZER
`
`3,863,049
`
`2
`
`The present invention is directed to an improved
`temperature control system. More particularly,
`the
`present invention is directed to a temperature control
`system for controlling the temperature of small vol—
`umes of liquid undergoing analysis in a centrifugal-type
`chemistry analyzer.
`,
`Centrifugal-type chemistry analyzers, such as the
`type disclosed in
`“Analytical Biochemistry",
`28
`545—562 (1969) introduce by centrifugal force small
`volumes of liquid sample and reagent, e.g., a combined
`volume of 300—600 milliliters into a series of cuvettes
`arranged around the periphery of a rotor. The reaction
`in the cuvettes is monitored with precision by photo-
`metric means. The reactions involved are usually tem-
`perature sensitive, with a constant temperature in the
`range of 25° to 40°C being usually required. Since the
`liquids involved in the tests are rarely at the desired
`temperature to begin with, and often are under refrig-
`eration until just prior to testing, it is important that a
`system be provided for raising and controlling the tem-
`perature of the liquids involved. Also, since most of the
`reactions involved in the use of centrifugal analyzers
`proceed rapidly, it is important that the temperature of
`the test liquid be brought rapidly, e.g., within about 30
`to 40 seconds, to the desired value and held closely at
`this value throughout the testing period.
`It is therefore an object of the present invention to
`provide a system for raising and accurately controlling
`the temperature of small volumes of test liquids in a
`centrifugal-type chemistry analyzer.
`Other objects will be apparent from the following de-
`scription and claims taken in conjunction with the
`drawing wherein:
`FIG. 1 is a sectional elevation veiw of a centrifugal
`type analyzer,
`FIG. 2 is a plan view of the analyzer of FIG. 1 show-
`ing means for applying heated air to the analyzer,
`FIG. 3 shows a series of curves representing various
`heating conditions in an analyzer of the type illustrated
`in FIG. 1,
`FIG. 4 shows a block diagram of the temperature
`control system of the present invention and,
`FIG. 5 shows a specific embodiment of a temperature
`control system in accordance with the present inven-
`tion. With reference to the drawing FIG. 1 shows in ele-
`vation a centrifugal—type analyzer comprising a remov-
`able sample-reagent disc 10 supported on a rotor 11
`and indexed theretoby pin 14. Rotor 11 is affixed to
`drive assembly 12 by pin 15. Drive assembly 12 is rotat—
`ably driven by way of v-belt pulley 13 attached to drive
`shaft 17. The portion 16 of rotor 11 is suitably of stain-
`less stell over which is arranged a glass plate 18. The
`body portion 20 of sample-reagent disc 10 is suitably
`formed of Teflon* and contains a plurality, usually
`about 30, of concentrically arranged inter-connecting
`cavities indicated at 22. Reagent cavity 24, contains for
`example a glucose reagent such as a 0.3 molar trietha—
`nolamine buffer of pH 7.5 containing 0.0004 Mol/liter
`NADP, 0.0005 MOI/liter ATP, 70 mg/liter hexokinase,
`140 m'g/liter glucose-6-phosphate dehydrogenase and
`0.004 Mol/liter MgSO4. The reagent, indicated at 26,
`upon spinning of the sample-reagent disc 10‘, passes
`into sample cavity 28, containing for example blood
`serum, and both liquids pass via transfer passage 30
`
`IO
`
`15
`
`20
`
`25
`
`30
`
`35
`
`into cuvette 32 located in ring member 34 which is af-
`fixed at 31 to rOtor ll. Cuvette 32, and all other cu—
`vettes, are enclosed by ring member 34 and are in that
`transfer relation therewith. Ring member 34 is formed
`of aluminum, coated for corrosion resistance purposes
`with a thin layer of Teflon* 35 in which is mounted a
`temperature sensing element, e.g., a thermistor, indi-
`cated at 36 which is adapted to provide an electrical
`signal indication of the temperature of the liquid in cu~
`vette 32. Cuvettes 32 are also provided with a thin Tef-
`lon* coating 33 for purposes of corrosion resistance.
`The extent of the reaction between the liquids in cu-
`vette 32 is measured photometrically by means of light
`source 38 and photomultiplier 40. The electrical signal
`derived from thermistor 36 is conducted via wire leads
`40 to slip rings 41 and to brushes 44 from which the sig’
`nal is conducted by wires 46 to the temperature con-
`trolling circuit illustrated in FIGS. 4 and 5 hereinafter
`more fully described.
`*Trademark of El. duPont de Nemours
`As shown in FIG. 1, the reaction in the cuvettes will
`take place within a substantially confined space'en—
`closed by metal housing 48, plastic ring shield member
`50 and plastic cap member 52. This arrangement essen-
`tially separates the interior of the housing from the out-
`side ambient temperature conditions. Hot air, con-
`trolled by the circuit of FIGS. 4 and 5 is introduced into
`the confined reaction environment at opening 54 and
`exits through openings 56 in housing 48. The general
`heating arrangement
`is illustrated in FIG. 2 which
`shows schematically a conventional blower motor and
`blower unit 60 which forces air over heating element
`62 through duct 64 and into housing 48.
`’
`With reference to FIG. 3 of the drawing, this Figure
`shows a series of curves, obtainable using a conven-
`tional “Brush” millivolt recorder which relate to the
`raising of the temperature ofa liquid in a cuvette 32 to
`a desired temperature. Curve A represents the charac—
`teristic variation of temperature with time in the cu-
`vette upon introduction of cold liquid into the cuvette
`without any heat being added. This characteristic varia-
`tion is obtained in the practice of the present invention
`due to the fact that the cuvette is located in a member,
`i.e., aluminum ring member 34, which has a substan-
`tially larger thermal mass than the liquid in the cuvette
`and is at the desired reaction temperature. Ring mem-
`ber 34 can be quickly raised to the desired reaction
`temperature simply by actuating the control circuit
`without any liquid in the cuvettes. The heat stored in
`the ring member is conducted to the liquid in the cu-
`vettes causing the cuvette temperature to rise as gener-
`ally indicated by curve A. The temperature control sys—
`tem of the present invention is most effective, if the'
`temperature of the liquid in the cuvettes be raised,
`without the direct application of heat, from an initial
`“cold” condition in the range of about 15°C to 20°C,
`to within 04° to 08°C of the desired value in the range
`of about 25°C to 40°C, within 20 to 40 seconds. This
`can be readily provided through the use of a metal ring
`member 34 having a thermal mass of about 5 to 20
`times or more of the thermal mass of the total liquid in
`the cuvettes. Aluminum is preferred for the ring mem-
`ber 34 because of its high heat conductivity although
`generally all structural metals and high heat conducting
`materials can be used. By way of example, the thermal
`mass of a 1 kilogram aluminum ring member would be
`1,000 X 0.23 (the specific heat of aluminum) or about
`
`'
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`v
`
`Page 7 of 10
`
`
`
`Page 7 of 10
`
`

`

`3
`
`3,863,049
`
`4
`
`230. The thermal mass of 12 grams of reagent plus sam-
`ple (95 percent or more water) would be 12 X 1 (the
`specific heat of water) or about 12. The ratio of the
`thermal mass of the ring to the liquid would be about
`20. A ring member of about 2,500 grams of copper
`would provide about the same ratio. Care should be
`taken in coating the cuvette with any substance that in-
`troduces significant thermal resistance between the liq-
`uid in the cuvette and the ring member so that the de-
`sired temperature increase is not unduly delayed. For
`example, a 3—7 mil Teflon“ coating has been found to
`be satisfactory where a ring to liquid thermal mass ratio
`of about 20 is provided. Referring further to FIG. 3, at
`time T, the temperature in the empty cuvette is the de-
`sired value, e.g., 30°C. The temperature in the cuvette
`is initially at the desired value, e.g., 30°C, due to prior
`heating of ring member 34 with hot air from the heater
`unit illustrated in FIG. 2. When cold liquid fills the cu-
`vette the temperature drops rapidly and then, on ac-
`count of the heat stored in the relatively larger rotor
`mass, and the small liquid volume in the cuvette, the
`temperature fairly rapidly rises. However the tempera-
`ture in the cuvette will never get within a tolerable
`value of the desired temperature, e.g., i0.1°C, indi-
`Cated at 100 without the addition of heat.
`‘Trademark of El. duPont de Nemours
`If excess heat is rapidly and continuously applied to
`the enclosed cuvette system from time T. to T2, the
`temperature-time relationship will be generally as indi-
`cated in curve B, i.e., the desired temperature will be
`reached rapidly and then exceeded by an undesirably
`large amount and will “over shoot” requiring a rela-
`tively long time to return to within an acceptable toler-
`ance of the desired value as indicated at T3. If, on the
`other hand, insufficient heat is applied, the situation
`approaches the condition of curve A.
`The desirable situation is illustrated by curve C when
`the temperature rapidly reaches the desired value and
`where any “over shoot” is within the acceptable toler-
`ance, e.g., about 01°C.
`This is accomplished in the present invention by the
`arrangement illustrated in FIGS. 4 and 5. With refer-
`ence to FIG. 4, the output voltage signal from the eu-
`vette thermistor 36 is applied to a standard bridge cir—
`cuit 100 having adjustments 101, 103 and 105 whereby
`the bridge circuit 100 will indicate a “zero” value when
`the signal from thermistor 36 corresponds to the pre-
`set desired temperature, e.g., 30°C. In the case where
`a cold sample is introduced into the cuvette, the signal
`from thermistor 36 will cause the bridge 100 to be un-
`balanced and a signal proportional to the temperature
`difference, indicated at 135, will be applied to amplifier
`110 to actuate trigger unit 120. Pulses from the trigger
`unit 120 are applied to a power switch 130 which per-
`mits alternating current power to be applied to how air
`heater 140 so long as pulses are received from trigger
`unit 120. The hot air from heater 140 is directed to the
`cuvette rotor assembly as previously described to raise
`the temperature in the cuvette. When the “no added
`- heat” profile (curve A) of the unit is approximately
`known as shown in FIG. 3, an initial “hold off" temper-
`ature can be estimated. This “hold off” temperature
`can be initially selected as about one half the total tem—
`perature drop, indicated at 145 in FIG. 3. This “hold
`of ” may be on the order of 2°C. With the approximate
`“hold off” value determined, “hold off” circuit 150 is
`set so that the output of rate limiter circuit 160 is iso-
`
`Page 8 of 10
`
`lated from the trigger circuit 120 by gate 165 for as
`long as the temperature in the cuvette is below the set
`“hold off" temperature. Under these circumstances,
`the signal from bridge 100 is applied via amplifier 110
`to trigger circuit 120 and heater 140 supplies heat to
`the cuvette containing ring member 34. When the tem-
`perature in the cuvette raises to the “hold off" level,
`the output of rate limiter circuit 160 will be applied to
`trigger circuit 120 by the closing of “hold off” gate
`165. Rate limiter circuit 160 detects the increase in
`rate of the output of amplifier 110, i.e., the rate of tem-
`perature increase in the cuvette. If the rate of tempera—
`ture increase is too fast, as compared to a predeter-
`mined value, i.e., an “over shoot" will eventually occur
`unless heating is discontinued, and under these condi-
`tions, a signal from the rate limiter circuit 160 “turns
`of ” the trigger circuit 120. Heat is no longer applied
`to the rotor assembly until the rate of temperature in-
`crease falls below the desired predetermined value, at
`which time the signal of rate limter 160 is no longer ap-
`plied to trigger circuit 120 and heat is again supplied to
`the rotor assembly. This operation continues until the
`desired temperature is reached and “zerO” output is
`present at bridge 100. The desired pre—selected rate of
`temperature increase to provide a temperature profile
`as indicated at “C” can be obtained by trial and error.
`Also, this rate can be initially approximated by obtain-
`ing a “no heat added” profile, such as curve A and
`marking off an increment equal to the maximum per—
`missable temperature tolerance, e.g., 01°C, as indi-
`cated at 115. The corresponding slope on curve A, in—
`dicated at 167, can serve as a first approximation of the
`maximum desired rate.'Further routine adjustment of
`the rate limiter circuit will optimize the heating cycle.
`In the event that with the initial “hold off" setting, the
`rate limiter circuit 160 never “turns on,” i.e., the maxi-
`mum desired slope is always exceeded,
`then lower
`“hold off” settings should be successively applied until
`the rate limiter circuit 160 becomes operative. The
`maximum rate setting can then be adjusted to minimize
`the time T4 required to reach an acceptable tempera-
`ture. For most tests using a centrifugal photometric an-
`alyzer, this time should be less than thirty to forty sec-
`onds.
`’
`With further reference to curve C of FIG. 3, illustrat-
`ing a temperature curve where temperature control is
`provided in accordance with the present
`invention,
`continuous hot air is supplied in the interval T. to T,'.
`Hot air is then turned off until the slope of curve C de-
`creases at 490 to just below the maximum desired slope
`500. Rate Limiter circuit 160 then causes hot air to be
`re-applied and the maximum desired rate of tempera-
`ture increase is essentially maintained until the desired
`temperature is achieved at 510, at which time the con-
`trol system is “off” since the voltage at the output of
`bridge 100 is “zero.” The cuvette temperature will then
`“over shoot” only within the desired tolerance. In the
`event that curve C goes below the desired tolerance at
`520 a signal will be developed at bridge 100 and trigger
`circuit 120 will cause heat to be re—applied and the tem-
`perature will be maintained within the desired toler~
`ance.
`'
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`4o
`
`45
`
`50
`
`55
`
`60
`
`65
`
`FIG. 5 illustrates more specifically the system of FIG.
`4. With reference to FIG. 5 the output of cuvette ther-
`mistor 36 is applied via slip rings 42 to bridge circuit
`100 which,
`in addition to thermistor 36, comprises
`fixed resistors 300 and 302 and the conventional ad-
`
`
`
`Page 8 of 10
`
`

`

`S
`
`3,863,049
`
`6
`
`_
`lO
`
`l5
`
`20
`
`25
`
`30
`
`35
`
`justable resistor arrangement which includes fixed re-
`sistors 306, 308 and 310 and adjustable resistors 312,
`314 and 316. Switch 318 is positioned to select the
`temperature value at which the bridge output will be
`“zero,” i.e., balanced, for the desired cuvette tempera-
`ture. For example, if the desired cuvette temperature
`is to be 30°C, switch 318 is placed in that position and
`a temperature of 30°C established in the cuvette. Ad-
`justable resistor 314 is then varied until the bridge out-
`put at 320, more practically, the amplifier output at
`340, is “zero.” The bridge circuit 100 is thus calibrated
`for a desired cuvette temperature of 30°C. The bridge
`can be similarly calibrated for other desired cuvette
`temperatures. The output of bridge circuit 100 is ap—
`plied to amplifierillo, for example a commercial dif-
`ferential amplifier Such as Fairchild ,u A 725. Custom-
`ary +15 VDC and -15VDC supplies to amplifier 110
`are provided at 322 and 324 respectively. A~conven—
`tional feedback circuit 326, c0mprising resistor 328
`and capacitor 330, is provided together with a conven-
`tional temperature balancing resistor 334. The output
`of amplifier 110 appears at resistor 338. By way of ex-
`ample, if the output of bridge circuit 100 is 0.02 volts
`for each degree Centigrade that the cuvette tempera-
`ture is below the desired temperature (which can be
`determined by routine calibration) amplifier 110 will
`provide an increased signal, e.g., 1 volt per degree Cen-
`tigrade, depending on the amplifier gain. Under these
`exemplary circumstances, if upon introduction of cold
`test liquid into the cuvette, the temperature drops from
`its initial value of 30° to 20°C, an output signal of 10
`volts will be provided at location 340 at the output of
`amplifier 110. This signal is applied at the input 342 of
`trigger circuit 120 and the input 344 of “hold off" cir-
`cuit 150. As shown in FIG. 5. “hold off” circuit 150
`comprises amplifier 344, which can be a commercial
`differential amplifier such as Fairchild u A741, which
`is provided with +15 volts and -15 volts at 346 and
`348. A reference voltage input signal for “hold off”
`amplifier 344 is provided by way of adjustable resistor
`350 and fixed resistor 352 supplied with +15VDC as
`indicated at 354. This reference signal from adjustable
`resistor 350 is the “hold off” signal. For example, if as
`previously noted, the desired cuvette temperature is
`30°C, and the cuvette temperature falls to 20°C upon
`introduction of cold test liquid, the “hold off” voltage
`at adjustable resistor 350 can be set to 5 volts as a first
`approximation, if the output of amplifier 110 is 1 volt
`per degree centigrade, as previously given by way of ex-
`ample. Under these circumstances, as long as the out-
`put of bridge amplifier 110 is more than 5 volts, a signal
`is provided at the output of “hold off” amplifier 344
`which, due to gate arrangement 165 (comprising di-
`odes 353 and 355), prevents an inhibiting signal from
`passing from rate limiter circuit 160 to trigger circuit
`120. Consequently, the signal from bridge amplifier
`110 is applied to trigger circuit 120 at 342, and causes
`electrical pulses to be applied to power switch 130
`whereupon AC power is passed through heater element
`62 of air heater 140 and hot air is delivered to the en-
`closure surrounding the cuvette as previously de—
`scribed, whereby the cuvette temperature is increased.
`Trigger circuit 120 can be a commercial unit such as
`Fairchild ,u A 742 and is arranged to receive an AC ref-
`erence signal at 356 by way of transformer 359, and
`DC power at 358 through the arrangement comprising
`resistors 360 and 362, diode 364 and filter circuit 366.
`
`With a positive signal applied to the trigger circuit 120
`at 342, output pulses appear at 367 and are applied via
`transformer 370 and power switch 130 to heater ele-
`ment 62 until an inhibiting signal, e.g., 15 volts DC is
`applied at 368.
`,
`Such an inhibiting signal will be applied when the
`output of bridge amplifier 110 increases greater than
`the pre-set rate of voltage increase due to the heating
`of the cuvette by hot air supplied from air heater 140.
`At this time, gate 165 will “open,"* permitting the sig-
`nal at the output 370 (if a signal is present) to be ap-
`plied at the input 368 of trigger circuit 120 which
`“turns off" the trigger circuit 120 discontinuing the ap-
`plication of hot air to the cuvette. Whether an inhibit-
`ing signal is present at the output 370 of the rate limiter
`circuit 160 depends on the rate of increase of the out-
`put signal of bridge amplifier 110 (which is propor-
`tional to the rate of temperature rise in the cuvette)
`and the desired maximum rate of cuvette temperature
`increase, determined for example in the manner previ-
`ously described in connection with FIG. 3. The rate of
`increase for the output signal of bridge amplifier 110 is
`detected by a conventional derivative circuit 372 com-
`prising capacitor 374 and resistor 376. The derivative,
`or rate signal obtained is applied at 378 to amplifier
`380, which can be a commercial differential amplifier
`such as Fairchild p.A74l. Amplifier 380 also receives a
`reference signal at 382 from temperature compensat-
`ing resistor 382, which corresponds to the desired max-
`imum rate and is set by adjustment of variable resistor
`384. For example, if the maximum desired rate of tem-
`perature increase is 0.01°C/second, the pre-set voltage
`at 382 would, neglecting off—set in amplifier 380, be
`0.88 millivolts for a typical value of 22K ohms for resis-
`tor 376 and 4 microfarads for capacitor 374. Any off-
`set in amplifier 380 can be taken care of by adjustment
`of variable resistor 384. For as long as the voltage at
`378 is larger in magnitude (more negative) than this
`value (0.88 mv) i.e., the rate of temperature increase
`is above the desired maximum, the output of amplifier
`380 is a positive signal, e.g., +15VDC, and an inhibiting
`signal is appliedvia gate 165 to trigger circuit 120 and
`heater unit 140 will be inactive. When, however, the
`voltage at 378 is lower than the pre—set value (0.88 mv)
`i.e., the rate of temperature increase is below the de-
`sired pre-set value, the output of amplifier 380 be-
`comes negative and this signal is blocked by diode 355
`whereupon trigger circuit 120, and hence heater unit
`140, is activated to supply additional hot air to the eu-
`vette and raise the temperature at a faster rate. This
`procedure then continues until the desired cuvette tem-
`perature is reached, e.g., 30°C, at which time the out-
`put of bridge amplifier 110 is “zero” and circuit opera-
`tion ceases.
`*(i,e., close the circuit)
`If it is desired to further reduce the time required to
`reach the desired cuvette temperature, the'pre-set rate
`voltage at 382 can be gradually increased while avoid-
`ing an undesirable temperature “over shoot."
`In the event that, with the initial estimated pre-set
`“hold off" voltage, the inhibiting signal of the rate lim-
`iter amplifier 380'is never applied to trigger circuit 120,
`i.e., the rate limiter never “cuts in,” the likelihood is
`that the “hold off" signal at 350, at the input to ampli-
`fier, is too small in magnitude and should be gradually
`increased in magnitude until the rate limiter 160 “cuts
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`Page 9 of 10
`
`
`
`Page 9 of 10
`
`

`

`7
`
`3,863,049
`
`8
`
`in" at least once before the desired temperature is
`reached.
`'
`By way of example, in the operation of a particular
`embodiment of the present invention the cuvette con-
`taining ring member (containing 30 cuvettes having a
`volume 0.45 to 0.6 milliliters each) was formed of an
`aluminum ring (cross section of approximately l%%in-
`ches X + inches) having an inner diameter of 5 1/2 inches
`and an outer diameter of 8% inches. The weight of the
`ring member was about ‘1 kilogram and the effective
`heat transfer area was 30—35 inz. The outer surfaces of
`the aluminum ring member, and also the inner cuvette
`surfaces, were coated with a layer of Teflon about 3—9
`mils thick. The aluminum ring member was located in
`an aluminum housing similar to the arrangement shown
`in FIG. 1. The outer diameter of the housing formed of
`Va inch aluminum was approximately. 10 inches and the
`height was about 6—7 inches. The housing was affixed
`to a base plate of 1/2 inch thick aluminum. The top of
`the housing was essentially closed by plastic members
`made of polystyrene. The ring member and sample-
`reagent disc were rotated at 1,000 RPM and the 30 cu-
`vettes were each filled with about 0.4 milliliters of sam—
`ple and reagent at a temperature of 15° to 20°C so that
`a total of about 12 grams of liquid was introduced into
`the cuvette containing ring member. Since the liquid
`was 95 percent or more H20, this is the thermal equiva—
`lent of about 12 grams of water. The aluminum cuvette
`containing ring member was initially at a temperature
`of 30°C, due to previous heating, which was the desired
`cuvette reaction temperature. Heated air was available,
`through a duct arrangement as indicated in FIG. 1, at
`about 65°C and 20 cubic feet per minute from a heater
`unit controlled by the system of the present invention.
`The desired reaction temperature of 30° C was reached
`within about 30 seconds and maintained within : 01°C
`by the action of the control system of the present inven-
`tion.
`The temperature control system of the present invenv
`tion has a high degree of flexibility. For example, with
`the system adjusted to provide a cuvette temperature
`control as indicated in curve C in FIG. 3, for the largest
`and coldest liquid sample to be handled by the centrifu-
`gal analyzer, smaller and less cold samples will be
`raised to the desired temperature (and maintained at
`this temperature) within the required time without any
`need for further adjustment of the system. Such smaller
`and less cold samples are indicated as curves D and E
`in FIG. 3. For curve D, heated air will be initially con-
`tinuously supplied for only the relatively short interval
`d after which heat control is provided by operation of
`
`the rate limiter circuit 160 in the manner previously de-
`scribed. For curve E, initial continuous heating will not
`be provided and heat control will be provided only by
`operation of rate limiter circuit 160. Of course, if de-
`sired, optimization of time required to raise the D and
`E type samples to the desired temperature can be
`achieved following the procedure previously described.
`I claim:
`1. A temperature control apparatus comprising a
`metal base member; a plurality of chambers adapted to
`contain liquid located within said base member in heat
`transfer relationship therewith, the thermal mass of the
`base member being substantially larger than the ther-
`mal mass of the thermal mass of liquid contained in the
`chambers; housing means substantially enclosing the
`base member and chambers to separate the base mem-
`ber and chambers from ambient temperature; a heating
`element adapted to develop heat by the passage of elec-
`trical current therethrough, means for passing air in
`contact with the heating element for the heating of said
`air and for introducing the heated air into the housing
`member to transfer heat developed in the heating ele—
`ment to the base'member and chambers to raise the
`temperature thereof to a desired value; temperature
`sensing means adapted to provide an electrical signal
`proportional to the amount by which a selected cham-
`ber is below the desired value; control means respon-
`sive to the signal of the temperature sensing means
`adapted to supply electrical energy to the heating ele-
`ment; rate detecting means for obtaining an electrical
`signal proportional to the rate of temperature increase
`of the selected chamber and for applying such electri—
`cal signal to the control means to inactivate the control
`means when the rate of temperature increase is above
`a predetermined value; means for preventing the signal
`from the rate detecting means from inactivating the
`control means as long [as the temperature of the se-
`lected chamber is below a predetermined value.
`2. An apparatus in accordance with claim 1 wherein
`said base member is formed of aluminum.
`3. An apparatus in accordance with claim I wherein
`chambers are enclosed within the base member and the
`thermal mass of the base member is at least about 5
`times the mass of liquid in the chambers.
`4. An apparatus in accordance with claim 1 wherein
`the chambers are enclosed within said base member,
`the base member is formed of aluminum, and the ther-
`mal mass of the base member is about 20 times the
`thermal mass of the liquid in the chambers.
`*
`*
`*
`*
`*
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`(15
`
`Page 10 of 10
`
`
`
`Page 10 of 10
`
`

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket