CA2111355A1 - Pipetting probe with reduced reagent carryover - Google Patents
Pipetting probe with reduced reagent carryoverInfo
- Publication number
- CA2111355A1 CA2111355A1 CA002111355A CA2111355A CA2111355A1 CA 2111355 A1 CA2111355 A1 CA 2111355A1 CA 002111355 A CA002111355 A CA 002111355A CA 2111355 A CA2111355 A CA 2111355A CA 2111355 A1 CA2111355 A1 CA 2111355A1
- Authority
- CA
- Canada
- Prior art keywords
- liner
- sheath
- pipetting probe
- inner diameter
- polymeric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0275—Interchangeable or disposable dispensing tips
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1004—Cleaning sample transfer devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1004—Cleaning sample transfer devices
- G01N2035/1006—Rinsing only the inside of the tip
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Clinical Laboratory Science (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The present invention embraces an improved pipetting probe wherein a portion of the interior of said probe is etched so as to create fluid turbulence therewithin during use to improve the washing out of residual sample fluid. More particularly, the pipetting probe of the present invention comprises a rigid tubular sheath (11) tightly circumscribing a tubular polymeric liner (12) wherein a portion of the interior of said polymeric liner is etched, particularly that portion excluding the sample region portion. The present invention also embraces a method of improving the internal washing efficiency of a pipetting probe by etching a portion of the interior of the pipetting probe. In addition, the invention embraces a method of making an improved pipetting probe by pulling a tubular polymeric liner, which has a narrowed liner portion formed by a narrowing die, into a rigid tubular sheath, and allowing the narrowed liner portion to expand against screw threads in the tip portion of the sheath so as to become immovably fixed therein.
Description
WO 92/~2379 P~/13S91/04203 ~111 35~
PIPETTING PROBE WITH REDUCED REAGENT CARRYOVER
Backqround of the Invention This invention relates to an improved pipett:ing probe.
Pip~tting probes are generally used in automatic diagnostic :
or analytical equipment and serve to extra t measured quantities o~ r~agents of various types from the containers which s~ore them and l~o dispen~e these raagents as required ~o conduGt ~he test or anaIy~is which is l~o be performed. `~
After eac:h extraction and dispensing of a parti;cular r~agent, the pipetting probe must be care:Eully washed, both inside and out, to remoYe all traces of that reagent in ord~r to prevent çont~mtna~ ion ~ the ~thex reagents and carryoYer of that re . gent into ~ubsequent tests . Since many :, diagnostic and analyticaI tests conducted i:n: automatic -.
equipment are capable cf making~ precise raeasurements in :the parts per~ million rang~, it is imperative that the pipetting probe which dispenses the reagents ~or such tes~s ba -designed such that it can be efficiently washe~ to remove al~poten~ial: co2ltaminants to a level below the normal ~: measuremsnt range of ~he instrument.
Ac~ ordir~glyr it is an object of the present invention :
to provide a pipetting pro~e which can be efficiently washed so as to reduce reagent carryover. It is also an object to : provide a met~od o~ making such: a pipe~ting probe~
3 0 The present in~rention embraces an improved pipetting prob~ wherein a portion of the interior of said probe is etc:hed so as to crea~e fluid t urbulence therewithin during use to improve: the washing out of residual sample fluid.
~qore partic:ularl~r, the pipetting probe of the pres~nt W092/22379 PCT/US91/042~3 '~11135~
in~ention comprises a rigid tubular sheath tightly circumscibing a tubular polymeric liner, wherein a portion of the interior of said polymeric liner is etched, ~`
particularly that portion exaluding the sample region portion. The present invention also embraces a method of impro~ing the internal washing ef f iciency of a pipetting probe by etching a portion of the interior o~ the pipetting probe. In addition, the invention embracec a method of making an improved pipetting probe by pulling a tubular :~
polymeric liner, which ~as a narrowed liner:portion formed by a narrowing die,:into a rigid tubular sheath, and ~
~~ allowing ~he narrowed liner portion to expand against screw .
threads in the tip portion of the sheath so as to become immovably fixed therein.
Brief Description of the Drawinas : Fig. 1 is a perspective view o~ the pipetting probe of the pres~nt invention and depicts both the rigid sheath, with 20 its tip portion, and the polymeric liner. '~
Fig. ~a is an enlarged cross-section of the tip portion of the rigid sheath and:depicts:the threaded section tshown by dashed lines) and the polymeric liner portion.
Fig. 2b is an enlarged cross-section of the opposite end of the rigid sheath and depicts the polymeric liner portion tightly circumscribed by the main portion of the rigid ~heath and extending out therefrom.
Fig. 2c is an even further enlarged cross-section of a fragment o~ the tip portion and depicts the threaded section therewithin.
Fig. 3 is a cross- ection of a narrowing die and depicts a portion of polymeric liner being drawn therethrou~h.
W092~22379 PCT/U~91/04203 ~1~13~5 ` `
Descri~tiQ~ of the Preferred Embodiments Throughout the specification and claims the te~ms reagent and sample fluid are used interchangeably and are S intend~d to include any fluid material used in a diagnostic or analytical test instrument . Such fluid materials include the sample being tested, for example patient samples, such as blood or urine or extracts~thereof, as well as standardized test samples, and the reagents utilized to conduct the test(s) to be performed, for example chemical, biochemical or biological reagents r ~including immunological ~~ r~agen~s suc~ as solutions of antibodies or antigens.
In its b~oadest application, the presen~ invention embraces a pipetting probe compri~ing a poly~ric tuhe having a discharge end into or from which a quantity of sample fluid may be drawn or discharged, wherein a~portio~ :.
of the interior of said tube is etched so as to create fluid ~:
turbulence therewithin during use~to improve the washing efficLency thereof. Pr~ferably that portion of the polymeric tube interior which is et~h~d excludes at least :
abouk the first 20%~of said~tube at the~discharge end, more preferably about the firct 30~ to 70% of ~aid tube at the : discharge end. Normally, the pipetting probe will comprise a sample region po~tion which extends ~rom the~discharge end 25 to~a pradatermined length of the polymeric tu~e. This i~ :
the portion which will hold a predetermined measured volume : ~
of sample ~luid. It is most preferred to exclude the:sample regisn portion from that portion o~ the polymeric tube interior which is etched. :
It has be~n found that etching a porti~n of the polymeric tube interior substantially increases the washing efficiency of the probe interior. It is theorized that when wash solu~ion i~ paæ~ed through the proba interior, it becomes turbulent as a result of contact with the etched interior wall. This turbulence then carries through the 2 1 1 1 3 ~ S ! ; :
non-etched portioh, which includes the sample region portion, and assists in the removal of any traces of sample fluid which otherwise might adhere to the smooth wall of the probe. Without such etchin~, the interior wall is 5 substantially smooth throughout, which results in a ;
substantially laminar flow of wash fluid through the probe ~.
(near-zero fluid velocity at the waIl surface). Such laminar flow i5 not very ~ffective at removing ~ample fluid that adheres to the interior wall.
The washing efficiency of the pipetting probe can be further improved by altering the inner diameter of the probe ~~ in certain sections. For example, it is particularly advantag~ous whe~e the tip portion of the polymeric tube (i.e. at the discharge end) has an inner diameter ~hich is `
narrower, preferably about 40 to 60~ narrower, than-the inner diameter of the major part of~the polymeric tube.
Most pref~rably, the polymeric~tube;will also have an intermediate portion, with an intermediate inner:diameter, between the tip portion and the major~part of the polymeric tube. This intermediate inner diametcr is preferably about 20 to 30% narrower than the major~part of the polymeric tube. The particulars of this geometry will be discussed in greater detail later.
The invention will now be more specifically described by reference to the accompanying~drawings, with particular emphasis on its most preferred embodiments.
The pipetting probe 10:, in its most practical form, comprises a rigid tubular sheath ll, preferably fabricated of stainless steel,~and a tubular polymeric liner 12, preferably fabricated of polyfluoroethylene. The rigid tubular sheath comprises a main portion 13 and a tip portion 14 at one end thereo~, said main portion 13 ha~ing a ~irst inn~r diameter and said tip portion 14 having a second inner diameter, with said second inner diameter being equal 35 to or less than said first inner diameter. Preferably said W~92/22379 PCl/~S9~/04203 2111~
second inner diameter is less than said first inner diameter, most prsferably about 25% less. It is also preferred that the tip portion 14 will have an outer ~-diameter which is less than the outer diameter of the main S portion 13 and will be connected to said main portion through angularly inolined neck portion 15, which serves as a transition between the tip portion and:the main portion.
The tip portion 14 has a diccharge end 16, into or from whîch sample~fluid may be drawn or discharged. This discharge end 16 is preferably cut at an angle (or beveled~
to facilitate the puncturing of sealed cartridges and the ~~ dispensing of fluid~ It is also especially preferred that a portion of the tip portion contain internal screw threads 20 for gripping the liner as will be discussed later.
In a typical pipetting probe which is proposed for use in the SRl instrument sold by Serono-Baker Diagnostics Inc., the rigid tubular sheath is fabricated from 15 gauge type 304 stainless steel tubing and has the following dimensions:
Tip Portion Length 14.0 mm (o.55 in) I.D. - 1.14 mm (0.045 in) O.D. ~ 5 mm (O.057 in) Main Portion Length - 124 ~m (4.88 in) I.D. - 1.52 mm (O.060 in) o.D. - 1.83 mm (0.072 in) Neck Portion Inclined at 13 angle from longitudinal axis Discharge End Beveled at 30 angle from perpendicular axis Screw Threads Extend 5 mm (0.2 in) from discharge end Thread size/pitch M 1.2 x 0.25 ~1113!~5'"' The tubular polymeric liner 12 is the more critical part of the invention since that is the part which holds the ~
sample fluid and which is the most difficult to wash of residual sample fluid after it is dispensed. Generally, the ~-5 polymeric liner is constructed of a flexible, inert, ~-non-wettable material such as polyfluoroethylene. Its len~th and inner diameter are selected ~o as to hold a predetermined quantity of sample fluid as a minimum (i.e.
the sample re~ion portion), plus some excess to serve as a buffer between the sample region portion and the operative machinery to which the liner is connected (e.g. Ca~ro ''~ syringe). While thè dimensions may be varied inversely wlthout aff~cting a change in the absolute ~olume of material held, there is a practical ran~e of values that is ~:
15 constrained by a need to measure and deliver acc:urate volumes, reduce pressure~drop, minimîæe surface:area, and f it within the instrument and sheath in which it is : utilized. This practical range of values ~ay be readily determined and optimized by the skilled practitioner. The outer~diameter of the polymeric liner should be approximately equal to or slightly greater than the inner diameter of ~he:rigid sheath (particular:ly~the main portion ~ of the sheath) so that, upon insertion, it is tightly : circumscribed and, preferably, immovably fixed therein.: It will be longer:~han the rigid sheath and will extend from the discharge end 16, to which it is preferably cut flush, through and beyond the opposite end of the sheath.
A preferred method of inserting and affixing the polymeric liner in the rigid sheath is now described, with particular reference to dimensions and materials that are characteristic of those proposed for use in the aforementioned SR1 diagnostic instrument. The sheath to which the liner is inserted is: the one previously described.
The polymeric liner utilized consists of polyfluoroethylene tubing (FEP tubing manufactured by Fluortek Medical Inc., Easton, PA) with an inner diameter of . W092/22379 PCT/US91/04203 ' l 7 1.07 mm (O.042 in) and an outer diameter of 1.74 mm (0. 068 in) . As will be app~rent, the outer diameter of this liner is slightly greater than the inner diameter of the main portion of tha stainle~s steel sheath, which is 1.5~ mm tO.060 in).
A portion of the liner is dra~n through a narrowing die 17, as illustrated in Fig. 3, to provide a narrowed liner portion 18 of 1.07 mm (0.042 in) outer diameter and 0.41 mm (0.016 in) inner diameter.
The outer diameter of the narrowed liner portion 18 is somewhat less than the:inner diameter of the tip portion 14, ~~ which is 1.13 mm (0.045 in), to facilitate easy inser~ion of tha liner within the sheath. For this reason the length of the narrowed liner portion is advantageousIy greater than the length of the sheath.~
Upon insertion of the:narrowed liner portion through the sheath, so that ~it extends~:through~the discharge end :
~thereof, it is pulled with the;necessary force so as to draw the~liner into the sheath, thereby narrowing that portion of the liner which en~ers the main portion of the sheath so as to form an intermiediate liner~portion 19 until:that intermediate:liner portion abuts~against~the;interior wall of the neck portion. The intermediate~liner portion 19 will thus be tightly circumsaribed by the main:portion 13 of the~
rigid sheath and will have a:length~and outer diameter~egual to the length and inner:diameter of the main portion of the rigid sheath. The inner diameter of the intermiediate liner portion is thius redueed to 0.71 mm (0.028 in).
Ths probe is then heated to about 200F (93C) for approximately two hours to allow the narrowed liner portion : to expand (due to memory characteristics of the material) : and become tightly circumscribed by he tip portion. This : expansion increases the inner diameter of the liner within the ip portion to 0.46 .i (0.018 in). This expansion also .
16 Rec~ P~T~I'I9 u ~
P~T~'uS 91~'~4203 ~111355 8 .
causes the narrowed liner portion to expand against the screw threads 20 and ~ecome immovably fixed within the tip portion. This is an important feature of the pre~ent invention since it substantially prevents movement of the :
liner away from the dischargQ end of the probe, which is a problem with csnventionally lined prob-~. After expansion of the narrowed liner portion, the liner is cut flush with the discharge end of the sheath and to a suitable length for the intended U5~ of the prob~, which in this case is 585 mm (23.0 in).
To further insure that th~ liner is i~movably fixed within th~ ~heath, it i~ preferred to apply adhe~i~e to '- either the int~rior of the sheath or th~ ~xt~xior of thE
liner prior to pu}ling t~e liner into th~ ~heath, then sub-~Qqu~ntly curing thQ adhe iv-. ~t is ~ost pr~f~rred to us~ an ~poxy adh~ive, ~uch ~ S~ooth-On: ~ -I3. To insura good bonding o~ th- adh~3iv~ to the poly~}uoroothyle~e : liner~,:the ext~rior sur~acQ Or the liner which will:come in : contact with ~h~ adhe $ve ~hould b~ ~tch~d with a chemical etchant,:such~ C~e~grip ~reating Ag~nt ~Norton company).
~ Th- pip~tt1ng p~ob~ described~abov~ is intended to m~a~ure sa~ple~ of approxi~ately 1~00 ~L to 225 ~ volume.
~ccordingly, the s ~ plQ region o~ th~ pro~e con~ist of : ~:
a~out th~ ~ir~t 335 2m ~ 13 in) ~starting ~ro~ th- discharg- :~
end. T~ ro~alnd~r Or the prob~, which i~ about 250 o ( 10 in) long, ~hould b~ etched ~on th~ int~rior ~surface~ with a cho~ical tc~ant, uch a~ Chemgrip Tr~ing Ag-nt. such etchlng changes the surface to a wettabl~ carbonaceou~ layer 2 which,- as ~tated previous1y~ creates rluid turbulence in the washing ~}ui~ which is pas~ed through th~ prob~ b-tween sa~plang, thereby inc~ea~ing the wa~hing ~rlci~ncy and su~antially.low~ring the carryover o~ sample ~luid.
Ths pipRtting prob~ of the~ pre~nt inv~ntion, a~ ::
describ~d abovQ, wa- tested ~or carryover o~ re~idual sampl~
fluid a~ter washing and thQ results co~pare~ to that ~rom a SUBSTITUTE SHEET
IPEAIUS
W092/22379 PCT/US~1/0~203 control probe which was used prior to this invention. The control probe is very similar to the inventive probe except that the polyfIuoroethylene liner i5 not etched and has an . inner diameter of 0.58 mm (0.023 in) at the tip portion and 1.07 mm (0.042 in) throughout the remainder of the liner.
The test used to measure sample carryover utilizes a sample well spiked with 1-2 x 106 mIU/ml of human chorionic gonadotropin (hCG). Diagnostic;testing of hCG is used to determine pregnancy. Generally, a measured hCG va}ue above 25 mIU/ml is a positive indication of pregnancy. Since .immunologic measurement of such levels of hCG is somewhat imprecise, it is extremely important to insure that the sample being measured is not contaminated with any hCG
carried over in the probe from a previous test. Thus, the ability to efficiently wash out an especially sticky substance like hG has been a difficul* problem to overcome.
The test protocol for sample carryover used to compare the performance of the inventive probe versus tl~e control probe involved the use of each probe in a conventional SRl diag~ostic instrument set up to read hCG levels from several control cartridge wells containing 10 mIU/ml hCG, ~ollowed by a spiked well containing 1-2 x 106 mIU/ml hCG, followed :~ : by a control well. The instrument was set to run its standard hCG assay under which the pipetting probe draws and 25 dispenses 100 ~l of hCG solution and is washed with about ~ ;
`
: 1.4 ml (about 1.0-1.2 ml internally) of a~buffered : surfactant wash solution. The hCG carryover from the~spiked well is the difference between the control reading~after the spike and the control reading before the spike. The~actual 30 quantity of hCG carryover is ¢onverted to parts per million (that is, parts:of hCG carried over per million parts in the spiked well) by dividing this difference by the amount o~
hCG in the spiked well.
~ollowing this protocol in repeated experiments, it has been ~ound that the control probe produces an hCG carryover W092/2237~ PCT/US91/04203 , . .
in the ange of 30-40 ppm. In contrast thereto, the probe of the present invention has been found to reduce the hCG
carryover to less than lO ppm, and generally to about - 2-6 ppm. This represents approximately a ten-fold improvement.
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'.
PIPETTING PROBE WITH REDUCED REAGENT CARRYOVER
Backqround of the Invention This invention relates to an improved pipett:ing probe.
Pip~tting probes are generally used in automatic diagnostic :
or analytical equipment and serve to extra t measured quantities o~ r~agents of various types from the containers which s~ore them and l~o dispen~e these raagents as required ~o conduGt ~he test or anaIy~is which is l~o be performed. `~
After eac:h extraction and dispensing of a parti;cular r~agent, the pipetting probe must be care:Eully washed, both inside and out, to remoYe all traces of that reagent in ord~r to prevent çont~mtna~ ion ~ the ~thex reagents and carryoYer of that re . gent into ~ubsequent tests . Since many :, diagnostic and analyticaI tests conducted i:n: automatic -.
equipment are capable cf making~ precise raeasurements in :the parts per~ million rang~, it is imperative that the pipetting probe which dispenses the reagents ~or such tes~s ba -designed such that it can be efficiently washe~ to remove al~poten~ial: co2ltaminants to a level below the normal ~: measuremsnt range of ~he instrument.
Ac~ ordir~glyr it is an object of the present invention :
to provide a pipetting pro~e which can be efficiently washed so as to reduce reagent carryover. It is also an object to : provide a met~od o~ making such: a pipe~ting probe~
3 0 The present in~rention embraces an improved pipetting prob~ wherein a portion of the interior of said probe is etc:hed so as to crea~e fluid t urbulence therewithin during use to improve: the washing out of residual sample fluid.
~qore partic:ularl~r, the pipetting probe of the pres~nt W092/22379 PCT/US91/042~3 '~11135~
in~ention comprises a rigid tubular sheath tightly circumscibing a tubular polymeric liner, wherein a portion of the interior of said polymeric liner is etched, ~`
particularly that portion exaluding the sample region portion. The present invention also embraces a method of impro~ing the internal washing ef f iciency of a pipetting probe by etching a portion of the interior o~ the pipetting probe. In addition, the invention embracec a method of making an improved pipetting probe by pulling a tubular :~
polymeric liner, which ~as a narrowed liner:portion formed by a narrowing die,:into a rigid tubular sheath, and ~
~~ allowing ~he narrowed liner portion to expand against screw .
threads in the tip portion of the sheath so as to become immovably fixed therein.
Brief Description of the Drawinas : Fig. 1 is a perspective view o~ the pipetting probe of the pres~nt invention and depicts both the rigid sheath, with 20 its tip portion, and the polymeric liner. '~
Fig. ~a is an enlarged cross-section of the tip portion of the rigid sheath and:depicts:the threaded section tshown by dashed lines) and the polymeric liner portion.
Fig. 2b is an enlarged cross-section of the opposite end of the rigid sheath and depicts the polymeric liner portion tightly circumscribed by the main portion of the rigid ~heath and extending out therefrom.
Fig. 2c is an even further enlarged cross-section of a fragment o~ the tip portion and depicts the threaded section therewithin.
Fig. 3 is a cross- ection of a narrowing die and depicts a portion of polymeric liner being drawn therethrou~h.
W092~22379 PCT/U~91/04203 ~1~13~5 ` `
Descri~tiQ~ of the Preferred Embodiments Throughout the specification and claims the te~ms reagent and sample fluid are used interchangeably and are S intend~d to include any fluid material used in a diagnostic or analytical test instrument . Such fluid materials include the sample being tested, for example patient samples, such as blood or urine or extracts~thereof, as well as standardized test samples, and the reagents utilized to conduct the test(s) to be performed, for example chemical, biochemical or biological reagents r ~including immunological ~~ r~agen~s suc~ as solutions of antibodies or antigens.
In its b~oadest application, the presen~ invention embraces a pipetting probe compri~ing a poly~ric tuhe having a discharge end into or from which a quantity of sample fluid may be drawn or discharged, wherein a~portio~ :.
of the interior of said tube is etched so as to create fluid ~:
turbulence therewithin during use~to improve the washing efficLency thereof. Pr~ferably that portion of the polymeric tube interior which is et~h~d excludes at least :
abouk the first 20%~of said~tube at the~discharge end, more preferably about the firct 30~ to 70% of ~aid tube at the : discharge end. Normally, the pipetting probe will comprise a sample region po~tion which extends ~rom the~discharge end 25 to~a pradatermined length of the polymeric tu~e. This i~ :
the portion which will hold a predetermined measured volume : ~
of sample ~luid. It is most preferred to exclude the:sample regisn portion from that portion o~ the polymeric tube interior which is etched. :
It has be~n found that etching a porti~n of the polymeric tube interior substantially increases the washing efficiency of the probe interior. It is theorized that when wash solu~ion i~ paæ~ed through the proba interior, it becomes turbulent as a result of contact with the etched interior wall. This turbulence then carries through the 2 1 1 1 3 ~ S ! ; :
non-etched portioh, which includes the sample region portion, and assists in the removal of any traces of sample fluid which otherwise might adhere to the smooth wall of the probe. Without such etchin~, the interior wall is 5 substantially smooth throughout, which results in a ;
substantially laminar flow of wash fluid through the probe ~.
(near-zero fluid velocity at the waIl surface). Such laminar flow i5 not very ~ffective at removing ~ample fluid that adheres to the interior wall.
The washing efficiency of the pipetting probe can be further improved by altering the inner diameter of the probe ~~ in certain sections. For example, it is particularly advantag~ous whe~e the tip portion of the polymeric tube (i.e. at the discharge end) has an inner diameter ~hich is `
narrower, preferably about 40 to 60~ narrower, than-the inner diameter of the major part of~the polymeric tube.
Most pref~rably, the polymeric~tube;will also have an intermediate portion, with an intermediate inner:diameter, between the tip portion and the major~part of the polymeric tube. This intermediate inner diametcr is preferably about 20 to 30% narrower than the major~part of the polymeric tube. The particulars of this geometry will be discussed in greater detail later.
The invention will now be more specifically described by reference to the accompanying~drawings, with particular emphasis on its most preferred embodiments.
The pipetting probe 10:, in its most practical form, comprises a rigid tubular sheath ll, preferably fabricated of stainless steel,~and a tubular polymeric liner 12, preferably fabricated of polyfluoroethylene. The rigid tubular sheath comprises a main portion 13 and a tip portion 14 at one end thereo~, said main portion 13 ha~ing a ~irst inn~r diameter and said tip portion 14 having a second inner diameter, with said second inner diameter being equal 35 to or less than said first inner diameter. Preferably said W~92/22379 PCl/~S9~/04203 2111~
second inner diameter is less than said first inner diameter, most prsferably about 25% less. It is also preferred that the tip portion 14 will have an outer ~-diameter which is less than the outer diameter of the main S portion 13 and will be connected to said main portion through angularly inolined neck portion 15, which serves as a transition between the tip portion and:the main portion.
The tip portion 14 has a diccharge end 16, into or from whîch sample~fluid may be drawn or discharged. This discharge end 16 is preferably cut at an angle (or beveled~
to facilitate the puncturing of sealed cartridges and the ~~ dispensing of fluid~ It is also especially preferred that a portion of the tip portion contain internal screw threads 20 for gripping the liner as will be discussed later.
In a typical pipetting probe which is proposed for use in the SRl instrument sold by Serono-Baker Diagnostics Inc., the rigid tubular sheath is fabricated from 15 gauge type 304 stainless steel tubing and has the following dimensions:
Tip Portion Length 14.0 mm (o.55 in) I.D. - 1.14 mm (0.045 in) O.D. ~ 5 mm (O.057 in) Main Portion Length - 124 ~m (4.88 in) I.D. - 1.52 mm (O.060 in) o.D. - 1.83 mm (0.072 in) Neck Portion Inclined at 13 angle from longitudinal axis Discharge End Beveled at 30 angle from perpendicular axis Screw Threads Extend 5 mm (0.2 in) from discharge end Thread size/pitch M 1.2 x 0.25 ~1113!~5'"' The tubular polymeric liner 12 is the more critical part of the invention since that is the part which holds the ~
sample fluid and which is the most difficult to wash of residual sample fluid after it is dispensed. Generally, the ~-5 polymeric liner is constructed of a flexible, inert, ~-non-wettable material such as polyfluoroethylene. Its len~th and inner diameter are selected ~o as to hold a predetermined quantity of sample fluid as a minimum (i.e.
the sample re~ion portion), plus some excess to serve as a buffer between the sample region portion and the operative machinery to which the liner is connected (e.g. Ca~ro ''~ syringe). While thè dimensions may be varied inversely wlthout aff~cting a change in the absolute ~olume of material held, there is a practical ran~e of values that is ~:
15 constrained by a need to measure and deliver acc:urate volumes, reduce pressure~drop, minimîæe surface:area, and f it within the instrument and sheath in which it is : utilized. This practical range of values ~ay be readily determined and optimized by the skilled practitioner. The outer~diameter of the polymeric liner should be approximately equal to or slightly greater than the inner diameter of ~he:rigid sheath (particular:ly~the main portion ~ of the sheath) so that, upon insertion, it is tightly : circumscribed and, preferably, immovably fixed therein.: It will be longer:~han the rigid sheath and will extend from the discharge end 16, to which it is preferably cut flush, through and beyond the opposite end of the sheath.
A preferred method of inserting and affixing the polymeric liner in the rigid sheath is now described, with particular reference to dimensions and materials that are characteristic of those proposed for use in the aforementioned SR1 diagnostic instrument. The sheath to which the liner is inserted is: the one previously described.
The polymeric liner utilized consists of polyfluoroethylene tubing (FEP tubing manufactured by Fluortek Medical Inc., Easton, PA) with an inner diameter of . W092/22379 PCT/US91/04203 ' l 7 1.07 mm (O.042 in) and an outer diameter of 1.74 mm (0. 068 in) . As will be app~rent, the outer diameter of this liner is slightly greater than the inner diameter of the main portion of tha stainle~s steel sheath, which is 1.5~ mm tO.060 in).
A portion of the liner is dra~n through a narrowing die 17, as illustrated in Fig. 3, to provide a narrowed liner portion 18 of 1.07 mm (0.042 in) outer diameter and 0.41 mm (0.016 in) inner diameter.
The outer diameter of the narrowed liner portion 18 is somewhat less than the:inner diameter of the tip portion 14, ~~ which is 1.13 mm (0.045 in), to facilitate easy inser~ion of tha liner within the sheath. For this reason the length of the narrowed liner portion is advantageousIy greater than the length of the sheath.~
Upon insertion of the:narrowed liner portion through the sheath, so that ~it extends~:through~the discharge end :
~thereof, it is pulled with the;necessary force so as to draw the~liner into the sheath, thereby narrowing that portion of the liner which en~ers the main portion of the sheath so as to form an intermiediate liner~portion 19 until:that intermediate:liner portion abuts~against~the;interior wall of the neck portion. The intermediate~liner portion 19 will thus be tightly circumsaribed by the main:portion 13 of the~
rigid sheath and will have a:length~and outer diameter~egual to the length and inner:diameter of the main portion of the rigid sheath. The inner diameter of the intermiediate liner portion is thius redueed to 0.71 mm (0.028 in).
Ths probe is then heated to about 200F (93C) for approximately two hours to allow the narrowed liner portion : to expand (due to memory characteristics of the material) : and become tightly circumscribed by he tip portion. This : expansion increases the inner diameter of the liner within the ip portion to 0.46 .i (0.018 in). This expansion also .
16 Rec~ P~T~I'I9 u ~
P~T~'uS 91~'~4203 ~111355 8 .
causes the narrowed liner portion to expand against the screw threads 20 and ~ecome immovably fixed within the tip portion. This is an important feature of the pre~ent invention since it substantially prevents movement of the :
liner away from the dischargQ end of the probe, which is a problem with csnventionally lined prob-~. After expansion of the narrowed liner portion, the liner is cut flush with the discharge end of the sheath and to a suitable length for the intended U5~ of the prob~, which in this case is 585 mm (23.0 in).
To further insure that th~ liner is i~movably fixed within th~ ~heath, it i~ preferred to apply adhe~i~e to '- either the int~rior of the sheath or th~ ~xt~xior of thE
liner prior to pu}ling t~e liner into th~ ~heath, then sub-~Qqu~ntly curing thQ adhe iv-. ~t is ~ost pr~f~rred to us~ an ~poxy adh~ive, ~uch ~ S~ooth-On: ~ -I3. To insura good bonding o~ th- adh~3iv~ to the poly~}uoroothyle~e : liner~,:the ext~rior sur~acQ Or the liner which will:come in : contact with ~h~ adhe $ve ~hould b~ ~tch~d with a chemical etchant,:such~ C~e~grip ~reating Ag~nt ~Norton company).
~ Th- pip~tt1ng p~ob~ described~abov~ is intended to m~a~ure sa~ple~ of approxi~ately 1~00 ~L to 225 ~ volume.
~ccordingly, the s ~ plQ region o~ th~ pro~e con~ist of : ~:
a~out th~ ~ir~t 335 2m ~ 13 in) ~starting ~ro~ th- discharg- :~
end. T~ ro~alnd~r Or the prob~, which i~ about 250 o ( 10 in) long, ~hould b~ etched ~on th~ int~rior ~surface~ with a cho~ical tc~ant, uch a~ Chemgrip Tr~ing Ag-nt. such etchlng changes the surface to a wettabl~ carbonaceou~ layer 2 which,- as ~tated previous1y~ creates rluid turbulence in the washing ~}ui~ which is pas~ed through th~ prob~ b-tween sa~plang, thereby inc~ea~ing the wa~hing ~rlci~ncy and su~antially.low~ring the carryover o~ sample ~luid.
Ths pipRtting prob~ of the~ pre~nt inv~ntion, a~ ::
describ~d abovQ, wa- tested ~or carryover o~ re~idual sampl~
fluid a~ter washing and thQ results co~pare~ to that ~rom a SUBSTITUTE SHEET
IPEAIUS
W092/22379 PCT/US~1/0~203 control probe which was used prior to this invention. The control probe is very similar to the inventive probe except that the polyfIuoroethylene liner i5 not etched and has an . inner diameter of 0.58 mm (0.023 in) at the tip portion and 1.07 mm (0.042 in) throughout the remainder of the liner.
The test used to measure sample carryover utilizes a sample well spiked with 1-2 x 106 mIU/ml of human chorionic gonadotropin (hCG). Diagnostic;testing of hCG is used to determine pregnancy. Generally, a measured hCG va}ue above 25 mIU/ml is a positive indication of pregnancy. Since .immunologic measurement of such levels of hCG is somewhat imprecise, it is extremely important to insure that the sample being measured is not contaminated with any hCG
carried over in the probe from a previous test. Thus, the ability to efficiently wash out an especially sticky substance like hG has been a difficul* problem to overcome.
The test protocol for sample carryover used to compare the performance of the inventive probe versus tl~e control probe involved the use of each probe in a conventional SRl diag~ostic instrument set up to read hCG levels from several control cartridge wells containing 10 mIU/ml hCG, ~ollowed by a spiked well containing 1-2 x 106 mIU/ml hCG, followed :~ : by a control well. The instrument was set to run its standard hCG assay under which the pipetting probe draws and 25 dispenses 100 ~l of hCG solution and is washed with about ~ ;
`
: 1.4 ml (about 1.0-1.2 ml internally) of a~buffered : surfactant wash solution. The hCG carryover from the~spiked well is the difference between the control reading~after the spike and the control reading before the spike. The~actual 30 quantity of hCG carryover is ¢onverted to parts per million (that is, parts:of hCG carried over per million parts in the spiked well) by dividing this difference by the amount o~
hCG in the spiked well.
~ollowing this protocol in repeated experiments, it has been ~ound that the control probe produces an hCG carryover W092/2237~ PCT/US91/04203 , . .
in the ange of 30-40 ppm. In contrast thereto, the probe of the present invention has been found to reduce the hCG
carryover to less than lO ppm, and generally to about - 2-6 ppm. This represents approximately a ten-fold improvement.
.,~' ' .
'~
:' ' :
:
.
~ ~: : : ;
' :, :: ' ~ ~
'.
Claims (23)
1. In a pipetting probe comprising a polymeric tube having an exterior surface and an interior surface and having discharge end into or from which a quantity of sample fluid may be drawn or discharged, the improvement wherein the interior surface of said tube beginning from said discharge end has in sequence a non-etched portion and an etched portion so as to create fluid turbulence therewithin during use to improve removal of residual sample upon washing.
2. The pipetting probe of claim 1 wherein the non-etched portion is about 30% to 70% of the length of said tube.
3. The pipetting probe of claim 1 comprising a sample region portion extending from the discharge end to a predetermined length of said tube, wherein the etched portion of the interior excludes said sample region portion.
4. The pipetting probe of claim 1, 2 or 3 wherein said polymeric tube is fabricated of polyfluoroethylene.
5. In a pipetting probe comprising a rigid tubular sheath having exterior and interior surface and a tip portion with a di charge end into or from which a quantity of sample fluid may be drawn or discharged, said sheath tightly circumscribing a tubular polymeric liner which is flush with said discharge end and extends through and beyond the end opposite the tip portion of said sheath, wherein said polymeric liner comprises a sample region portion extending from said discharge end to a predetermined length of said polymeric liner, the improvement wherein the interior of said polymeric liner excluding said sample region portion is an etched portion so as to create fluid turbulence therewithin during use to improve removal of residual sample fluid upon washing.
6. The pipetting probe of claim 5 wherein said polymeric liner is fabricated of polyfluoroethylene and said rigid tubular sheath is fabricated of stainless steel.
7. A pipetting probe comprising a rigid tubular sheath comprising a main portion and a tip portion at one end thereof, said tip portion connected to said main portion through an angularly inclined neck portion and having a discharge end into or from which a quantity of sample fluid may be drawn or discharged, said tip portion having an outer diameter and an inner diameter which are less respectively, than an outer diameter and an inner diameter of said main portion, and a tubular polymeric liner tightly circumscribed by said sheath, said polymeric liner being flush with said discharge end and extending through said main portion and beyond the and opposite the tip portion of said sheath, a portion of said liner, beginning at said discharge end and extending for a predetermined length therefrom, comprising a sample region portion for holding a predetermined volume of said fluid, the interior of said liner, excluding said sample region portion, being an etched portion so as to create fluid turbulence within said liner during use to improve removal of residual sample fluid upon washing.
8. The pipetting probe of claim 7 wherein said tip portion comprises internal screw threads and said polymeric liner is embedded therein so as to prevent longitudinal movement of said liner within said tip portion.
9. The pipetting probe of claim 8 wherein the inner diameter of said polymeric liner within the tip portion is about 40 to 60% of the inner diameter of said polymeric liner which extends out of the sheath.
10. The pipetting probe of claim 9 wherein the inner diameter of said polymeric liner within said main portion is about 70 to 80% of the inner diameter of said polymeric liner which extends out of the sheath.
11. The pipetting probe of claim 10 wherein there is adhesive between said polymeric liner and said sheath.
12. The pipetting probe of claim 11 wherein said discharge end is bevelled.
13. The pipetting probe of claim 7, 10 or 12 wherein said polymeric liner is fabricated of polyfluoroethylene and said rigid tubular sheath is fabricated of stainless steel.
14. A method of improving the internal washing efficiency of a pipetting probe having exterior and interior surfaces which comprises etching a portion of the interior of said pipetting probe.
15. The method of claim 14 wherein said pipetting probe has a discharge end and comprises a sample region portion extending from the discharge end thereof to a predetermined length of said pipetting probe, said sample region portion being excluded from said etching.
16. The method of claim 15 wherein said pipetting probe is fabricated of polyfluoroethylene.
17. A method of making a pipetting probe which comprises: providing a rigid tubular sheath having exterior and interior surfaces and comprising a main portion and a tip portion at one end thereof, said main portion having a first inner diameter and said tip portion having a second inner diameter, said second inner diameter being equal to or less than said first inner diameter; providing a tubular polymeric liner longer than said sheath and having an outer exterior surface whose diameter greater than said second inner diameter; forming screw threads within said tip portion; drawing at least a portion of said liner through a narrowing die so as to form a narrowed liner portion with an outer diameter less than said second inner diameter; pulling said liner into said sheath so that it extends from each end thereof, with said narrowed liner portion aligned with and extending from said tip portion; allowing said narrowed liner portion to expand against said screw threads so as to become immovably fixed within said tip portion; and cutting said liner flush with said tip portion.
18. The method of claim 17 additionally comprising applying adhesive to a portion of the interior of said sheath or the exterior of said liner prior to pulling said liner into said sheath and curing said adhesive after pulling said liner into said sheath.
19. The method of claim 18 additionally comprising etching, prior to said pulling, that portion of the exterior of said liner which will come in contact with said adhesive to improve the bonding thereof.
20. The method of claim 19 wherein said tip portion has an outer diameter and inner diameter which are less, respectively, than an outer diameter and inner diameter of said main portion and is connected to said main portion through an angularly inclined neck portion, and said liner is pulled into said sheath until that portion of the liner which was not narrowed abuts said neck portion.
21. The method of claim 20 wherein said liner initially has an outer diameter greater than said first inner diameter.
22. The method of claim 21 wherein said liner comprises a sample region portion extending from the end which is cut flush with the tip portion to a predetermined length thereof, and wherein the method additionally comprises etching the liner interior, excluding said sample region portion.
23. The method of claim 22 wherein said sheath is fabricated of stainless steel and said liner is fabricated or polyfluoroethylene.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002111355A CA2111355A1 (en) | 1991-06-13 | 1991-06-13 | Pipetting probe with reduced reagent carryover |
| JP3514042A JPH06508428A (en) | 1991-06-13 | 1991-06-13 | Pipetting probe that reduces reagent carryover |
| EP91914994A EP0588791A1 (en) | 1991-06-13 | 1991-06-13 | Pipetting probe with reduced reagent carryover |
| PCT/US1991/004203 WO1992022379A1 (en) | 1991-06-13 | 1991-06-13 | Pipetting probe with reduced reagent carryover |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002111355A CA2111355A1 (en) | 1991-06-13 | 1991-06-13 | Pipetting probe with reduced reagent carryover |
| PCT/US1991/004203 WO1992022379A1 (en) | 1991-06-13 | 1991-06-13 | Pipetting probe with reduced reagent carryover |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2111355A1 true CA2111355A1 (en) | 1992-12-23 |
Family
ID=4152615
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002111355A Abandoned CA2111355A1 (en) | 1991-06-13 | 1991-06-13 | Pipetting probe with reduced reagent carryover |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0588791A1 (en) |
| JP (1) | JPH06508428A (en) |
| CA (1) | CA2111355A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111565849A (en) * | 2017-12-28 | 2020-08-21 | 富默乐有限公司 | Pipette tip and method for automatically maintaining pipette tip depth in fluid |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009276214A (en) * | 2008-05-15 | 2009-11-26 | Hitachi High-Technologies Corp | Immuno-analyzer |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4210156A (en) * | 1978-04-24 | 1980-07-01 | Bennett Elmer T | Finger stick blood collection apparatus |
| JP2839560B2 (en) * | 1989-07-10 | 1998-12-16 | 株式会社日立製作所 | Particle suspension mixing device, particle suspension mixing method, and particle measuring device |
-
1991
- 1991-06-13 EP EP91914994A patent/EP0588791A1/en not_active Withdrawn
- 1991-06-13 JP JP3514042A patent/JPH06508428A/en active Pending
- 1991-06-13 CA CA002111355A patent/CA2111355A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111565849A (en) * | 2017-12-28 | 2020-08-21 | 富默乐有限公司 | Pipette tip and method for automatically maintaining pipette tip depth in fluid |
| CN111565849B (en) * | 2017-12-28 | 2023-06-02 | 富默乐有限公司 | Pipette tip and method for automatically maintaining the depth of a pipette tip in a fluid |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0588791A4 (en) | 1994-05-04 |
| JPH06508428A (en) | 1994-09-22 |
| EP0588791A1 (en) | 1994-03-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |