CA2000580A1 - Occult blood sampling device and assay - Google Patents
Occult blood sampling device and assayInfo
- Publication number
- CA2000580A1 CA2000580A1 CA002000580A CA2000580A CA2000580A1 CA 2000580 A1 CA2000580 A1 CA 2000580A1 CA 002000580 A CA002000580 A CA 002000580A CA 2000580 A CA2000580 A CA 2000580A CA 2000580 A1 CA2000580 A1 CA 2000580A1
- Authority
- CA
- Canada
- Prior art keywords
- specimen
- sample
- receiving portion
- panel
- liquid
- 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
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/505—Containers for the purpose of retaining a material to be analysed, e.g. test tubes flexible containers not provided for above
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0038—Devices for taking faeces samples; Faecal examination devices
-
- 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
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/505—Containers for the purpose of retaining a material to be analysed, e.g. test tubes flexible containers not provided for above
- B01L3/5055—Hinged, e.g. opposable surfaces
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
- G01N33/721—Haemoglobin
- G01N33/726—Devices
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/805—Test papers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/81—Packaged device or kit
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/807—Apparatus included in process claim, e.g. physical support structures
- Y10S436/808—Automated or kit
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/807—Apparatus included in process claim, e.g. physical support structures
- Y10S436/81—Tube, bottle, or dipstick
Abstract
ABSTRACT
The invention provides a disposable device for collecting, transporting and storing semi-solid or liquid specimens prior to analysis. A sample of the collected specimen is removed from the device for analysis by means of a detachable transferring stick, one area of which is the sample collecting portion of the device and another area of which is an integral handle. The device also provides for the collection of a liquid sample drained from a defined volume of a semi-solid specimen through a porous screen and collected on the detachable transferring stick. A sample of the specimen or liquid from it may be flushed from the stick for a qualitative or quantitative determination of analyte.
The device is useful in collecting fecal specimens and detecting occult blood therein by a determination of hemoglobin in the specimen itself or in a liquid sample drained therefrom.
The invention provides a disposable device for collecting, transporting and storing semi-solid or liquid specimens prior to analysis. A sample of the collected specimen is removed from the device for analysis by means of a detachable transferring stick, one area of which is the sample collecting portion of the device and another area of which is an integral handle. The device also provides for the collection of a liquid sample drained from a defined volume of a semi-solid specimen through a porous screen and collected on the detachable transferring stick. A sample of the specimen or liquid from it may be flushed from the stick for a qualitative or quantitative determination of analyte.
The device is useful in collecting fecal specimens and detecting occult blood therein by a determination of hemoglobin in the specimen itself or in a liquid sample drained therefrom.
Description
`-`" 20(:~0580 OCCULT B~OO~ sAMP~Ip~ DRVICe AND A~8Ay 5Thl- appllcatlon i- a oontlnuatlon-ln-part Or U 8 `~ Applicatlon S-rlal No 258,036, fll-d Octob-r 1~, 1988 EASXG~QU~ OF THE INVEN~QN
~-` The present inv ntion r late~ to dl~po~abl- d-vlce~ for ---th collectlon, tran-port, and torag- Or a ~p cl~en prlor to analy-i- for a co pon nt th-r of, and p clrlcally to an ~U~ lntègral ;f atur w~ich provld - for conv nl nt r moval Or a ampl- of th coll-c d p c~-n Th~ ~pr --nt lnv-ntlon ~ also r~lates to assay~ tor olubl- co~pon nt- ln color d or ; 15 opaque semi-~olld sp ci~ ns, and sp~ci~lc~lly to a ~thod for obtalning a li ~ - ~ l- rr ~-uc ~ in ns ~ -coll~ction,~ tran~po ~ atlon`~ and ;~-toff g of any type~of ~peoi~ns~ for d lay d~rout~n ~ànaly-l- r-quire-a ff iate and ~-ffici-nt pack 1 ~ nekag 8 ~r 0~ ~ ~ 8~ of~; ~ ~ ially inf ~e~lln~ical~biologieal ~ -u ond~
t~ r t 1 ~ ~ ~ ~ ~ ~ ~
r sùlt can b obsc ~ ~by t ~ ~ f,~ 1 d at lal of `; -~ 30 the~ ~p~ci~n ~ At th ~a~ ti -, how v r, conventiona}
f ` ~ i ol~tlon~ ~ r-- ~ar~ i~ Nct~c l~`ln~ e Or r utin~`''!:''''''' ~ ~' ~ed~ca~l~ t--t~ hieh~ u-t b- proe ---d eonoaieally h refore~-pecl~ v b -n ~d ~ l~op~d to ~n~lyze e~s--~ pecia~n~ lntwt, without flr t --xtraetlng ~a liquid 35~ o pl~
8p~eci~ n~: of f-cal~ at~rial ar co_only coll ct-d and ail-d to a co~ rclal laboratory~ ~or ~ly l~ for occult .. , ~ - - . .
2QOQ~80 blood This type of ~p-ein n 1- a paradig of th- p-ci~-n eolloeting and analy-l- dlffleultl-- lndleat-d A numb-r of fecal o¢cult blood t--t y-t-~- u-- di-po-abl-, -alabl-colleetlng devlees ~ultable for torag- and tran-port of a feeal specimen preliminary to the analy~is for he~oglobin These tests usually incorporate a r agent for the guaiac test, capable of detecting h-~oglobin in an intact f-cal specimen Guaiac chemistry i~ ba~-d on the ability of he~oglobin present in blood to act a~ a p-roxida~-, releasing 2 fro~ peroxlde to ¢hang th eolor of an indicating guaiacum r sin to a blu color U S Patent No 4,225,557 to Hartl disclos-~ a typical physical design for an occult blood test, which provide~ an area having an absorbent surface and impregnated with guaiac, mounted within a frame on a rigid panel of a folder, onto which a fecal specimen i8 applied After the speci~en is collected, a flap of the folder eovers th- absorbent surface and ~eals At this point, tho ~y~tea i- table, and the device ~ay be taken or ailed to a laboratory, where the test for hemoglobin is perfor~ed To te~t for th pre~one-~ of hemoglobin, a few drops of hydrogen poroxide aro appli-d to the exposed underside of the ab-orbent layer The peroxide passes through to react with any h -oglobin present in the speci~en, and in a positive t st, the guaiac in the absorbent layer is converted to a blue color Th eolor is conveniently observed, free o* interference by th opagu , ~- colored speci~en, on the sa~e underside of the absorbont layer This form of the te~t ha~ a nu~bQr of defect- and thoy have been ~et by a series of nodification- and i4prove~ent~
First, guaiac i8 easily oxidized to a blu color on prolonged expo8ure to air Therefor , it ~u-t b- prot-ct d fro~ oxidation in order to prev nt ineorr ct results, and its effectiveness verified at tho ti~e the a--ays aro 35 perfor~ed U S Patent No 4,382,064 to Detwiel-r t al discloses a coating for surfaces in contact with guaiac in the device, the coating comprising the antioxidant BHT
incorporated into a varnioh appll-d to th- ~urfaa-~ U 8 Patent No 4,365,970 to L~ur-ne- t al di~olo--- on-d id-positive and negativ- p-rfor~anee ~onitor~ for the guaiac test wherein the po-itive eontrol eompri~- a h-moglobin component Another defect in the guaiac test for oeeult blood is that it is ub~eet to interf-rence from other oxidative reaction~ in the speci~en which give ri~e to fal-e po~itive results One souree i8 that of peroxida--~ pr ~ent in foods whieh apparently ~urvive the dige~tiv proe-s~ and re~ain aetive in fecal ~aterial U S Pat-nt No ~,333,734 to Fleischer discloses an improved guaiae ehemi-try which comprises inhibitors of co~peting peroxida~es Another i~
that of oxidizing agent- used to olean toilet bowl~ from which the specimens are usually retrieved, and U S Patent No 4,675,160 to Talmage et al discloses test eontrols to detect this source of interference Another problem is that these tests do not provide for reproducible sampling For even qualitative tests to be reliable and significant from te-t to te~t they should be carried out on a defined preferably constant, specimen volume U S Patent 4,273,741 to Levine diseloses a ~ -, -.",, .. , -constant volu e stooI testing devie- wherein the speei~en is applied to a surfaee eontaining an area whieh is a reeessed grid That portion of speeimen r~aining above the grid is ~- ~ removed before the test is performed The eonsequenees of a false positive oecult blood test, indicating colo-rectal bleeding, are seriou~ ine it requires the consideration of more serious im asive ~i 30 diagnostic procedures For this reason, it is eustomary to eonfirm a positive oeeult blood test with a ~ore ~peeifie test for hemoglobin To verify the test rQsults independently, for example, by inmunoassay for bemoglobin, it is often neeessary to ~eeure a ~nple of the fluid phase of the speGimen, substantially uneontaminated by olid material One oecult blood te~ting device provides for a guaiae 2~0058~) test for hemoglobin together with simultaneous ~iampllng of a liquid filtrate of the fecal oipe¢imen. U.8. Patent No.
4,645,743 to Baker disclose~ a fecal te~ting device comprising an absorbent specimen pad having a pocket in which is inserted a second liquid sampling sheet. The specimen pad can be inserted and mounted in a rigid frame which comprises a 6ample receiving sheet impregnated with guaiac. After a fecal specimen is deposited on the absorbent pad, it is placed, specimen side down, in the frame against the receiving sheet. The guaiac test is performed in the conventional way, by applying a few drops of peroxide on the underside of the receiving ~heet. The second sampling layer, the insert, receives a liguid portion of the fecal specimen which has filtered inwardly from the absorbent pad. The insert, containing the liquid sample, can be removed and cut into portions from which the retained liquid can be eluted and assayed by any desired procedure, for example, a radioimmunoassay.
Methods similar to the ~iaker device for follow-up or supplementary testing are unsatisfactory in a number of ways, and can lead to incorrect results.
First, a liguid sample which has been filtered through a volume of an absorbent pad may be less concentrated and it6 composition not representative of the original liquid sample. Absorbent material exerts an initial chromatographic effect on the solutions passing through it, retarding the passage of large molecules with respect to smaller molecules, particularly thiose of water. Unless thie total volume of the liquid in the specimen is sufficient to saturate the pad and thus overcome this effect, the filtered liquid sample will be diluted and its relative composition distorted by the extraction of larger molecules.
The liquid content which will flow from most semi-solid biological specimens is usually quite limited. The effect of collecting a small volume of filtered liquid therefrom through an absorbent pad in almost all cases will be to reduce the sensitivity of any 6ubsequent test, especially ~.~,< ,, :.
2000581~) with respect to the large molecul--Further, unleso the liquld ~a~pl- ¢oll-ct-d on the receiving ourface 1- drain-d from a d-fln-d ~a-pl- volum-and collected in a deflned ar a, th- r-~ult~ of a ~uboegu-nt assay are unreferenced and cannot b compar d over a period of time or from sub~ect to ~ub~-ct Again, the sensitivity of testing cannot bo defined There are other difficulties in attempting to collect a liquid sample from a fecal pecimen in con~unction with a guaiac test In th- use of d-vice~ ~uch a- that of Bak r, the portion of the insert containing the liquid ample muot be cut or punched from the insert, a process which reguir s unsanitary contact ~nother ma~or problem with ~uch devices iB that they must sit for a substantial period of time before they are analyzed Often, this involves transit through the mails, under a wide variety of ambient conditions of temperature and humidity Sticking together of parts of the collection device is a ma~or problem, a6 is drying and possible 108~ of portions of the specimen Such collections also risk the contamination of the liguid sample with wet guaiac indicator diffu~ing from the specimen receiving sheet In addition, the device as `::
disclosed and similar devices are complex and expensive to ~ -fabricate Immunological tests for hemoglobin are presently available in rapid, convenient, easily interpretable colorimetric form quivalent or superior in ~ensitivity to `~ the guaiac test Further, solid-phase ixmunoassays can concentrate analyte from dilute sa ples, thus achi-ving higher sensitivity than colorim tric chemistries Such ,~
`~ tests may be substituted for the guaiac test as a pri ary rather than confir atory proc~dure if there is a means provided to obtain an appropriate liquid or semi-liquid sample from the fecal ~pecimen A1BO~ in an i~ unological te~t for occult blood, ~ust as in the guaiac test, a time ~-lap~e between the collection of the specimen and the " ~-'' ~.,' hemoglobin ao~ay does not aff-ct th- aecuracy of th- r--ult Accordlngly, the de~ign of a f-cal p-cl~-n coll-ctlng devlce for occult blood t-~tlng dlr-ct-d only to th-eollection o~ an appropriat- llquld fraetlon can b fr -d from the reguirem-nts and r -trietion- of th- guaiae chemistry Devices whieh ean eoll-et f-eal apocimen~ for analy~i~
wlthout commitment to a deflned chemistry can also be u~-d to collect any semi-solid ~peciaen in an analogou~ way lo Such peci~ens can be blood clot-, vo~itu-, ~putum, pu-, or olid tissue The collect-d materlal can then b-conveniently eluted and analyzed for a vari-ty of ubstance-according to appropriate analytical proc-dur ~, rath-r than restricted to an 1~ sJtu colorimetric chemical analysi~
It is therefore an ob~ect of the invontion to provide a device capable of collectlng a liquld or ~emi--olid specimen and providing for convenient sampllng therefrom Another ob~ect is to provide a conv ni-nt, ~anitary, folding sample devic- that can b ~hipp d through the mall or stored for a period of time with gr atly reduced drylng and sticking problems It is further an ob~ect of the invention to provide a device capable of collecting a sample of liquid fro~ a se~i-soli~d specimen wherein tho sample accurately r pr -ents tho native composition of the liguid It i8 also an ob~ect of the invention to provide a ~ ~device capable of eollecting a representatiY sa pl- fro~ a -~` defined volume of the sp~cimen It is further an ob~ect of the invention to provide a i 30 device which allows for the sanitary and conv ni~nt re oYal -~ ~ of a sa~plo of the thu~-collect d ~p cimen- to a -parate t-st device It is further an ob~oct of the invention to proYide a procedure whereby a saaple collectod fro a focal pecimen in the device of the invention is thon analyzed for hemoglobin by a solid-phase enzy e iD unoassay, and this procedure is a screoning te~t for oceult blood , . , It i8 further an ob~-et of the lnventlon to provlde a deviee eapable of eonveniently eolleetlng a repre~entatlvo sample from a llquld or ~-ml-~olld ~p-el~-n, whleh d-vie-ean be easily and in-xpen~lv-ly fabrieat-d from a unltary blank SU~ARY oF~
The device of the preoent lnventlon provide~ a ~eans to collect a sample of a se~l-~olld ~p el~en, a llguld or a sample of the liquid eomponent of a eml-solld ~peelmen Preferably, the speel~ n 1~ a blologleal p elmen The device also provides a means to r move the eollected sample from the device by means of an integral detachable transferring stick The detaehable strip has an integral lS handle which i8 used to remove it, together with the eollected sample, from the device A collected sample is eluted from the detachable strip by a volume of solvent, and sample~ of this volume ean then be analyzed, both by gualitative and guantitative ~eans According to one aspeet of the invention there is provided a system for use in the eolleetion of a sample used in the analysis of a liquid or ~emi-~olid speei~en, eomprising a sampling folder having a front panel, a back panel, and a specimen reeeiving portion eovered by the front panel, the two panels being in overlylng relationship to one another, and the front panel b ing openable to permit applieation of a speei~en to the p-eimen r eeiving portion An area of this ~pecimen reeeiving portion comprises material onto which a ~peeinen ean be applied, and whieh is 0 eapable of retaining the speei~en In a preferred embodiment, the speei~en i- a biologieal peei~en The speeimen receiving portion eomprises, at least in part, a detachable sample transferring stick having a handle portion and a sample collecting portlon In one obodiment, the sample transferring stiek is a part of the back panel In another embodiment, the sample transferring ~tiek i8 attaehed to the inside of the back panel According to 2~0058~
another embodiment of thi~ a-pect of th- lnvention, a central leaflet between th- tront and back pan-l~ compri~
the ~peci~en rec-lvlng portlon In thl- mbodl~ nt, th-sa~ple transrerring tlck may comprl~- a part of th- c-ntral 5 leaflet In another bodi~ nt, the tran-f-rr~ng ~tlck 1-attached to the back of th c-ntral l-afl-t In a partlcularly preferred e bodl~ nt, the c-ntral l-aflet is a bilayer of two panels, wher in one of th- pan-ls comprises the specimen r ceiving portion and th- other co prises th-10 sample collecting portion The ~pecimen r-c-iving portion of th- ~ampling d-vice ~ay compri-e, at least in part, a heet of porou- ~aterial, in front of the speciJ n appllcation ar-a to which th-specimen can be applied, wherein the porous material is 15 adapted to permit only a portion of th- specimen to be transferred through the porous ~aterial onto the speci~en - receiving portion In on- embodi~ent of th- inv-ntion, wherein the specimen is g nerally opaque, the ~peci~ n application area includes indicia thereupon which r main 20 visible only when a predeter~ined a~ount of specl~en of less than that amount has b en applied ther to ~o that a us-r can determine that the a~ount of speci~ n appli-d does not ~ exceed the predetermined a~ount -~ In a particularly advantag ous e~bodl~ent, the specl~en 25 recelving portion is porous ~at-rial that has been coated with a release agent to pr vent sticking of the specinen to the porous ~aterial and to prevent sticking tog ther of the - various layers of the sa~pllng devlce In yet another embodl~ent of the lnvention, th back 30 panel includesi-a ~eans for providing a opening through which the sample transf rring stlck can b r noved -`~ In a partlcularly pref rr d bodivent, th pan l~ and th- stick of the inv-ntion ar for~-d fro~ cellulo~ic ~aterial The 6ample collecting portion of the tran~iferring 35 stick ~ay also have an additional layer of ab-orbent ~aterial thereon According to another aspect of the invention, there is ,. , , " . , .
2~00586) :
provided a sampling device a~ part of a kit whleh further comprl-e- a aixing eup; a liguid for u-- ln th- aixing cup to xtract the ~ampl- fro~ aid ~ampl- coll-etlng portion7 and a assay devie- for d-t-r~ining th- pr-~-ne- or guantlty s of an analyt- in th- extr~et-d ~ampl- In a pref rred embodiment, the speei~en i~ a ~tool ~aaple and the analyt-i8 hemoglobin In yet another bodiaent of thi~ aspeet of the invention, the a~ay d-viee in fora of a kit includes a receptacle for holding the eup The eup aay be built into 10 the device According to yet another aspect of the --invention, there i~ provid-d a thod for eoll-eting and ~-analyzing a specimen compri6ing the ~tep- Or opening the front panel of the sampling folder applying a ~peei~en to the specimen application area of the peci~en reeeiving portion elosing the front panel; and thereafter removing the sample transferring stick by gra-ping only the handle ;~ portion thereof, 80 that contact betw n a u~er and a ~ample iB avoided during the ample re~oving t-p and analyzing - the sample on the sample collecting portion of the removed stick for the pre~enc- of an analyt- In a pref-rr d embodiment, the specimen is a stool peeiaen and th analyt-is hemoglobin In a partieularly pr f rr-d ~ bodiaent, tho analyzing step eompris-s an i~ unoa~say In a partieularly preferred embodiment the ~ampling d-viee in th eontext of a 2s kit is a sampling deviee in whieh the speei~ n reeeiving portion comprises at least in part a heet of eoated or non-eoat-d porous material in front of a peei en applieation ;
ar a to which the pecia n ean be applied, wh-rein th-~ porous material i8 adapted to per it only a pred t r in d --i 30; amount of the speci~ n to be transf rr d to the porous aat-rial onto said specim n r eeiving portion Th eoating ~at-rial i~ pr ferably a rel-a-e agent that pr ~ nt- dri d sample from stieking to the porou- aat rial in pref~r nee to the specimen receiving portion -BRIEF DESCRIPTION OF THE DRA~N~-s ~ -Figure 1 is a front vi-w of a pr ferred e bodl~ent of -~
. ~.
' -~' 200(~58~
the folded sampling device Figure 2 i8 a back view Or th- ~old-d ~mpllng d-vlc-Figure 3 is a p-rspective vi-w Or th- a~pllng devic-with the front cover lifted, xpo~ing th- xt-rlor ~urface of the specimen application panel Figure 4 is a perspective view Or the s~pling device with the openable flap Or the back end lirted, xposing the exterior surface of the liquid sample collecting panel Figure 5 is a planar view Or the fac- ~ur~ace Or the unitary blank from which th- sampling dev$c- i~ tolded Figure 6 i~ a planar vi-w of tho r-verse ur~ace o~ the unitary blank from which the sampling device is folded DETAILED DESCRIPTION OF TNE INVENTION
The sampling device 2, according to a preferred embodiment illustrated in Figures 1 through 6, contains a sampling bilayer 48 ncloo-d as a central leafl-t between a iront panel 10 and a back panel 12 The sampling bilayer 48 consists of a specimen receiving panel 14 and a sample collecting panel 16 The front surface of the folded sampling device 2, as best seen in Figure 1, is made up of the front panel 10 which is folded down over the exterior surface of the specimen receiving panel 14 The front cover 10 is held in place by the insertion of its lower edge into a semi-circular slit 22 cut into the specimen receiving ~ panel 14 ;~ The front panel 10 has on its face surface 6 printed matter which may include title~ and trademark, and indicated areas for recording infor ation The back surrace of the folded sampling device 2, as best seen in Figur 2, is the back panel 12 The back panel 12 has an openable flap 18 `~ which i~ defined by an open slit 26, perforated ide edges 28 and a fold line 29 in the area proximal to the kack panel In the folded sampling device 2, the specim n receiving panel 14 and the sample collecting panel 16, lie with their reverse surfaces 8 together to form a bilayer central s~- - .. ... ; ............................................................ :
2~00580 leaflet 48 The ~pecimen receiving panel 14, a~ b-~t ~--n ln Flgur-3, iB expo~ed by lifting the front pan-l 10 m e ~pecimen receiving panel 14, in addition to th- -mi-eireular slit 22 has a pair of punched-out open specimen applie~tion area~ 20 located in the upper half of the panel The punched-out open specimen application areas 20 are filled by a porous screen 30 attached to the reverse urface 8 a~ best seen in Figure 6 The sample collecting panel 16, ~a best seen in Figur-4, is exposed by lifting the openable flap 18 of the back panel 12 The sample collecting panel 16 comprises a pair of detachable sample transferring stieks 24 having a tip 36, a ~ample collecting area 38, and an integral handle 40 The sample sticks 24 are defined by perforated or notched edges 32 Porous screen 30 may also be eoated, to reduce the likelihood that the sereen 30 wiil adhere to sample sticks 24, especially in sample collecting area 38, when samples are collected or transferred The device may alternatively comprise a monolayer central leaflet consisting of the speci~en receiving panel 14 enclosed between the front 10 and back 12 panels In this embodiment, the back panel 12 also serves a~ the sample collecting panel 16 and the transferring sticks 24 are integral parts thereof In another embodiment of this type, the back panel 12 may be a solid sheet and the transferring sticks 24 are attached to the interior side thereof 80 as to underlay the open ~ample applieation areas 20 of the specimen receiving panel 14 Alternatively, the eentral 1 30 leaflet may comprise the transferring sticks The ~ampling deviee 2 may be used to eolleet a sa~ple ~- of a liquid or ~e~i-solid speeimen in ither a defined or undefined volume A defined volume of ~ liguid or ~emi-solid speci~en may be eollected, or a liquid sample may be taken from a eolleeted semi-solid speeimen The open speeimen areas 20 provide for sampling a specimen of a defined volume A defined speeimen ,; ' ` - 2~10Q58C) application area i8 defined by th- geometry of the open specimen areas 20. The ~pecimen volume may be defined by filling an open speclmen area 20 with a ~emi-~olld ~poclmen to the depth of the porou~ screen 30. The porou~ screen 30 preferably ie one with large openings: that is a ~creen with a coarse mesh.
The specimen volume which i8 then retalned in the screen and predetermined by the size of the openings and the depth of the porous screen 30 may in this way be transferred through the porous material and onto the speclmen recelvlng portion.
~ he sampllng device 2 may also be used to collect a defined sample volume of seml-solld specimen according to constructions that eliminate the filter screen 30. For example, the specimen receiving area 14 (which may be identically the sample collecting area 16) may be imprinted with graphic symbols or other indicia which become obscured when an adequate amount of an opaque specimen is applied.
A defined volume of a liquid specimen can be sampled by providing an area of defined absorbency, for example in the open specimen applications areas 20, or on the sample collecting portion 16 of the device 2 and applying the specimen thereto.
The device alco provides for obtaining a liquid ~ample from a defined volume of a ~emi-solid specimen. A liquid sample taken from a semi-solid specimen may be used for either a qualitative analysis for the presence of components or a quantitative analysis for the concentration of components. A liquid sample for qualitative analysis may be collected from a relatively small semi-solid specimen through an absorbent filter on the specimen receiving surface or onto an absorbent layer on the sample collecting surface. If the amount of fluid sample that passes through an absorbent filter is large enough to overcome chromatographic effects which alter the concentration of its components, the liquid sample may be analyzed quantitatively. A liquid sample for quantitative analysis ~ .. . . .
. . ~ ~,. . . .
~,,," ~, ~ " "
~,. ~ . -, , ~-. :, ,,. . - -2~0058~1 may be collected from ven a relatively ~mall amount of ~pecimen by u~ing a form of th- a-ple d-vice havlng no absorbent filter or collectlng urfae-~ Th- ~ample thu~
collected accurately repr-~ent~ the concentration and composition of the liguid pre~ent in the native specimen, in that it retains higher molecular weight ~pecies which are freguently lost due to chromatographic effects in low volume filtrations Liguid i6 drained from a volume of semi-~olid specimen defined by the geometry of a collection space The liguid drains through a filtering screen of non-absorbing porous material, and onto the liguid coll-eting urface of a detachable strip The drained ~pecimen is retained on th-filter 6creen by adherence thereto and by self-adherence and viscosity A liquid sample is collected from a semi-solid specimen in the device 2 by opening the front panel 10 to expose the pecimen receiving panel 14, and applying the specimen to the open specimen areas 20 at a uniform depth to fill the filter screen 30 within, using an imple~ent such as a 6patula, flat stick or 6mall spoon Excess specimen is wiped from all areas of tho specimen receiving panel 1~
except the open specimen areas 20 After the specimen is applied, that area of the liguid sample collecting panel 16 underlying the open speci~en area 20 becomes wetted by liguid seeping through the porou~ filter screen 30 Particles smaller than the pores of the porous filter sereen 30 may also be transferred to the sample collecting panel Modifications of the s~mpling device 2 that provide various degrees of separation of solid and liguid components can be provided by ad~ustments in the porosity of the filter screen 30 In addition, the filter screen 30 ay be coated with a release agent, to deerease the likelihood that sample colIection area 38 of the sample sticks will adhere to the screen The release agent ean be selected from any of various suitable materials Polyhydroxy compounds seem to be ~.
.
2~0058 particularly suitable; however, wator solubl- poly~er~ ~nd fatty materials, such a~ liquid fatty aoid- and triglyceride~, al80 wer- found to be ff-ctlv- Polyhydroxy compounds are well known and an xhaustlv~ t can r adlly be generated by those of klll in th- art Th-~e materlal~
include, but are not limited to, variou~ ~ugar~, lncluding pentoses and hexoses, poly ers of alcohol~, lecithin, alkylene glycols, and the liko While ~ome r lea~e agents functioned more effectlv-ly than oth-r~, almost any (preferably liquid) matorial that can i~prognate and/or coat the fibers of the filter scr en 30 can b~ used to advantage in the invention For example, the following solutions were tested O S%
- 1% polyvinylpyrrolidone (PVP - Calbiochem Corp , La Jolla, 15 CA); 0.25~ - 1% polyethylen~ glycol (PEG - J.T. Bak~r, Jackson, TN) 0 1% - 1% Tween 20 ~Sig~a, St Louis, M0) : ~ PA~ cooking spray (an aerosol of partially hydrogenated vegetable (soy) oil and lecithin, d ~crib d in U S Pat-nt No 4,188,412)(Boyle-Nidway, Inc , NY, NY); and 6 25% - 100%
sucrose (Sigma, St Louis, M0) The coated screens were compared with non-coated filt-r screen in preventing ~ticking of the scrQen to the ~ample collecting portion 16 i~mediately and ~5 minutes after mearing fecal samples The filter screens coated with 0 5%
25PEG, 0 25% PEG, 1% PEG, 1% PVP, 12 5% sucrose and PAM!
:
appeared to be better at preventing stickiness th~n the non-coated filter screen The best solutions for prev nting stickines6 were 0 5% PEG and PAM!, but PAM~ was difficult to work with The Tween 20 ~olutions ~ignificantly incr ased the stickiness of the filter ~cre-ns compared with non-coated screens ; We also tQsted the ffocts of 0 5% PEG and 12 5%
sucrose for interference, ~ensitivity and ~tability in running a hemoglobin (Hb) test Several non-coat-d, 12 5%
sucrose, and 0 5% PEG coated filter screens fecal ~ ple packets were smeared with either a negative fecal ~u~pl- or a spiked fecal sample (2mg Hb/g sample) Three packets from 2~00580 :, `
;.
each group were allowed to dry ~or 45 ~inute~, 24 hour~, and on- week, respectiv-ly, berore t-~ting Th-y w r- lther kept at 4 C, room te~p-rature, 37 C, or ~5 'C Upon running the Hb test on th- pack-t~, O S% PEG and 12 5% ~uero~- did not interfere wlth th- t-~t Ther- w r- no fal~- po-itlve~
or false negatives, and th-y appear d to be ~u~t a~
sensitive as the packets tested with non-eoated filter screen stored at the sa~e te~peratur-The sampling device 2 ~ay aloo b u~-d to eollect an undefined sample volume of intact ~peei~-n, wh-ther liguid or semi-solid, according to o bodi~ nt~ that li~inat- th-filter screen 30 In these e bodi~ nt-, the ~p ci~en ~ay be sampled by direct application to th- a~pl- eoll-eting portion 16 of the device or peeifieally to the ~a~ple area 38 of the transferring stieks 24 in any of th-ir various attachments This may be done aeeording to several arrangements First, the devie ay be ade up with the bilayer 48 eentral leaflet of th pr f rr d bodi~ent, but without the filter sereen 30 In thi- eonfiguration, the speei~en ean be applied directly to th- ~a~pl- eoll-eting portion 16 through the open speeinen applieation areas 20 Secondly, the device ~ay be anufaetured with a ~onolayer central leaflet coaprising identically the sp ci~en receiving portion 14 and the ~a~ple collecting portion 16, and the specimen applied direetly th reon Alternatively, ~, ........................................................................ .
the device may be ~anufactured without a central l-aflet, whorein the inner surface of the back panel 12 ay ~-rve as -the specimen receiving portion 14 or th e~ ple eoll-eting portion 16 i 30 Other arrange~ents can be developed that eonfor~
; to the general requirQ~ents of th inv ntion, and retain th f-atures of the preferred o bodi~ent The sampling device 2 uay bo anufactur d fro~ variou~
~aterials, such a cellulosic, paper or eardboard toek, ;~
plastie or plastic eoated e-lluloie ~aterials, or nitrocellulose, provided any sueh stoek has nough rigidity ~
to maintain the shape of the funetional feature~ The ~--. ~,:
2~100580 material for the filter screen 30 ~hould b- non-absorbent or have a mlnimal absorbency Th- mat-rlal u--d for the fllt-r o¢r-en 30 1B of a uniform thlckne~ ~o that together with the fixed open spe¢imen area~ 20, it d-fln-- a pecimen volume when lt 18 in plac- in th- ~p-¢im n application panel 14 In order to do this it should also have ~ufficient structural rigidity BO that it retains a stable porosity when compressed by a ~pecimen load In a preferred embodiment, the filter screen 30 i8 of nylon mesh, and 1B
preferably coated with a release agent The material used for the ~ampl- tran~ferring ~tick~ 24 need not be either absorbent or porous Self-adherent biological specimens, for example, particularly those that are proteinaceous adhere to the surface of the transferring sticks 24 The liquid volumes which are collected on the sticks 24 is small in most applications and can adhere to the collecting surface by capillary action or as a moisture film The liquid collecting capacity of the tran~ferrinq sticks 24 can be conveniently expanded, when reguired, by an added layer of absorbent material on the surface of the liquid sample transferring sticks 24 The added layer Day be a sheet of filter paper or particles of bibulous material, for example, cellulose flake~ or dry Sepharose beads `~ 25 After the specimen is coll-cted, the lower flap of the front panel 10 is inserted in the semi-circular ~lit 22 of the specimen receiving panel 14 BO as to close the sa pling device 2 The enclosed specimen may now be stored or transported in the device The period the peci~en can remain in the device and the conditions of torage are determined according to the stability of the analyte The sampling device 2 can ultimately b- conveniently discarded The collected samplQ i~ re-oved from the device 2 for analysis by maans of the transferring sticks 24 To remove the sample according to the device of the preferred embodiment, one of the transferring sticks 24 int gral to the sample collecting panel 16 is removed by means of an ., handle 40 provided by lts di~tal nd Th- tran~if-rrlng ~tlcks 24 are loo~ely held ln th- ampl- coll-ctlng panel 16 by attachments at the tip 36 and at polnt- along th-perfor~ted edge~ 32 These attach ent~ ar- a-lly torn by a S ~light pull on the handle 40 Thus, when the tran~ferring stick 24 is grasped at its handlo 40, it can be pulled free from the device 2 In other embodiments, wherein the transferring sticks 24 are attached to the interior side of the back panel 12 by an adhesive substance, they may be similarly pulled free The sample collecting area 38 Or th tran~ferring tick 24 retains a sample of either the intact ~pecimen, which may contain solid particles, an intact liquid ~pecimen, or a sample of liquid which has been drained from a semi-solid specimen The sample is eluted from the transferring stick 24 by a volume of aquieous solution A sample which has been collected on the sample transferring stick 24 can be eluted for the deter ination of - an analyte therein, or an analysis, for example a colorimetric determination, may be performed directly on the stick 24 In a preferred embodiment of the invention, co~prising a companion immunoa~say procedure a8 described b low, any solid particles present in the sample are filtered from the solution in the course of the assay procedure The sampling device 2 is conveniently incorporated into a kit, which also comprises ~aiterials and reagents for determining a particular analyte together with an elution cup or vessel which is conveniently used to transfer a collected liquid sample from the transferring sticks 24 of the sampling device 2 into a ~easured volume of liquid The elution liquid may also be provided a8 a component of the kit In a preferred embodiment, the sampling device 2 is a component in a kit which provides a solid-phage enzy~e immunoassay device together with accessory reagents for the immunological determination of hemoglobin Two such devices k'~
~ 00580 are de~cribed in U 8 Pat-nt Applleatlon- 8-r~al No~
909,020 and 189,049 ar- eonv-nl-ntly adapt-d to th-determlnation of hemoglobln ln a llquld ~a~pl- Th-~-devices eo~prises a porou~ ue~bran- whleh ~ay have antlbody to hemoglobin bound to its upp r ~urfaee and whieh is flxed in a rigid housing Absorbent aterial below the ~embrano acts to wick liquid away from the ~a~ple Any of the samplQ states dlseus~ed above, that 1~, a solid specimen or liquid drained fro~ th- ~p ci~en, ay be analyzed for hemoglobin accordlng to th- proe-dur A oolld sa~ple of the fecal ~peci~en carri-d on the transferrlng tick is eluted using about 200 ~ierolit-r~ of elution volume in the cup provided A portion of the luted e~i-solid or liquid sample is then introdueed into the assay deviee through a prefilter, which re-oves any particulate ~atter, and then onto the surfae- of th- ~e~brane Any hemoglobin present in the sample 18 bound by the antl-~ he~oglobin antibodiQs of th ~embran , whlle unbound ;~ ~ubstances pass through the ~e~bran~ The he~oglobin ~olecules thus bound to the ~urfaee of the ~ brane are then contacted with a volume of solutlon eontainlng Qnsyse-labeled anti-he~oglobin antibodies and are bound also by these Alternatively, the he~oglobin ~olecule ~ay be bound initially by labelQd anti-he~oglobin antibodiQs present in the elution liquid When th enzyme thus bound to he~oglobin i8 allowed to react with a chro~ogenic substrate, -~ the presence of color indicatQs the presencQ of he~oglobin :~:
Control arQas of the ~e brane are preparQd with approprlate reagents to bind the d tecting antibodies in the absene~ of hemoglobin (positive eontrol) or to bind neither these antibodies nor the hemoglobin (n gatlvo eontrol) Aeeording to the pr~ferred bodi~ent, the sa~pling device 2 is for~ed fro~ a unitary blank 4 as best -en in Figures 5 and 6 and having a faeQ surfae- 6 (Figure 5) and a rQvQrsQ surfacQ 8 (Figure 6) The blank co~pri-~s four panels in sequence a front panel 10, a back panel 12, a speci~en application panel 14 and a liquid samplQ eollecting . ; 2nooss~
panel 16 The ends of ad~oinlng pan-l~ ar uark-d by fold line 42, lying betw -n th- a~pl- eoll~etinq pan-l 16 and the specimen applleation pan-l 14, fold lln- ~4, lylng between the specim n applicatlon pan~ and th- baek pan l S 12, and fold line 46 betw en tho ba¢k pan l 12 and the front panel 10 The face eurfaee 6 of th blank ~ eompri~es thoo-surfaces of the panels that fac- outwardly ln the folded device 2; the reverse surface 8 eomprl~eo thooe ~urfaces of the panels that face lnwardly ln the folded devlee 2 --The sampling device 2 i8 ror~ed by foldlng from the unitary blank 4 The 8ampl- eollecting pan l 16 i8 folded back along fold line 42 and against th- epoeim n application - panel 14 with their reverse urfaces 8 togeth r, o that th-sample transferring sticks 24 underlie the specimen lS application area 20 The back panel 12 io then folded along fold line 44 80 that its rever~e surrace 8 io in contaet ;~ with the face ~urface 6 of the oample eoll-etion panel 16 ~ --The front panel 10 is then folded along fold line 46 80 that its reverse surfaee 8 is in eontact with th- face surfac- 6 ~-of the specimen application panel 14 In thi- way, the ~; ~ sp~cimen applieation panel 14 and th a ple eolleetion panel 16 forn a sampling bilayer e ntral l<afl~t ~8 betw on the back panel 12 and the front panel 10 The sampling device 2 ay be used to coll-et samples froa a vari-ty of liquid or ~e~i-solid ~p eimens such as foods, soils, manufaeturing wastes, or pref-rably biologieal samples Appropriate eemi-solid biologieal speeimens are blood elots, sputum, ~UCOU8, pU~, vouitus, ~- gastrie content6, wound debris, gross tissu fro~ urgieal -~
30 `epecimens or biopsi-s, or fecal atter ~-The collected liquid or ~emi-solid a pl- ay be u- d to determine any substanc or ntity ther in, any inorganie or organic chemical ~peei-e, biological mol-eul-s uch a- -enzymes, proteins, lipids or earbohydrates, inf etious -agents such as viruses, bacteria or parasites, eell typ~s present in the speei~ n, or toxins ~any other ob~eets, features, and advantages of th~
: . .
2~t0(~580 present inventlon will be apparont to thos~ Or ~klll in the ~,~
art Although the inv-ntlon has been d-~¢ribed in tor~ of certain preferred embodiment~i, it will b- under~itood that the invention i8 intended only to be li~ited by the lawful scope of the claims that follow, ~nd eqjuival-nts thereor . j .
~-` The present inv ntion r late~ to dl~po~abl- d-vlce~ for ---th collectlon, tran-port, and torag- Or a ~p cl~en prlor to analy-i- for a co pon nt th-r of, and p clrlcally to an ~U~ lntègral ;f atur w~ich provld - for conv nl nt r moval Or a ampl- of th coll-c d p c~-n Th~ ~pr --nt lnv-ntlon ~ also r~lates to assay~ tor olubl- co~pon nt- ln color d or ; 15 opaque semi-~olld sp ci~ ns, and sp~ci~lc~lly to a ~thod for obtalning a li ~ - ~ l- rr ~-uc ~ in ns ~ -coll~ction,~ tran~po ~ atlon`~ and ;~-toff g of any type~of ~peoi~ns~ for d lay d~rout~n ~ànaly-l- r-quire-a ff iate and ~-ffici-nt pack 1 ~ nekag 8 ~r 0~ ~ ~ 8~ of~; ~ ~ ially inf ~e~lln~ical~biologieal ~ -u ond~
t~ r t 1 ~ ~ ~ ~ ~ ~ ~
r sùlt can b obsc ~ ~by t ~ ~ f,~ 1 d at lal of `; -~ 30 the~ ~p~ci~n ~ At th ~a~ ti -, how v r, conventiona}
f ` ~ i ol~tlon~ ~ r-- ~ar~ i~ Nct~c l~`ln~ e Or r utin~`''!:''''''' ~ ~' ~ed~ca~l~ t--t~ hieh~ u-t b- proe ---d eonoaieally h refore~-pecl~ v b -n ~d ~ l~op~d to ~n~lyze e~s--~ pecia~n~ lntwt, without flr t --xtraetlng ~a liquid 35~ o pl~
8p~eci~ n~: of f-cal~ at~rial ar co_only coll ct-d and ail-d to a co~ rclal laboratory~ ~or ~ly l~ for occult .. , ~ - - . .
2QOQ~80 blood This type of ~p-ein n 1- a paradig of th- p-ci~-n eolloeting and analy-l- dlffleultl-- lndleat-d A numb-r of fecal o¢cult blood t--t y-t-~- u-- di-po-abl-, -alabl-colleetlng devlees ~ultable for torag- and tran-port of a feeal specimen preliminary to the analy~is for he~oglobin These tests usually incorporate a r agent for the guaiac test, capable of detecting h-~oglobin in an intact f-cal specimen Guaiac chemistry i~ ba~-d on the ability of he~oglobin present in blood to act a~ a p-roxida~-, releasing 2 fro~ peroxlde to ¢hang th eolor of an indicating guaiacum r sin to a blu color U S Patent No 4,225,557 to Hartl disclos-~ a typical physical design for an occult blood test, which provide~ an area having an absorbent surface and impregnated with guaiac, mounted within a frame on a rigid panel of a folder, onto which a fecal specimen i8 applied After the speci~en is collected, a flap of the folder eovers th- absorbent surface and ~eals At this point, tho ~y~tea i- table, and the device ~ay be taken or ailed to a laboratory, where the test for hemoglobin is perfor~ed To te~t for th pre~one-~ of hemoglobin, a few drops of hydrogen poroxide aro appli-d to the exposed underside of the ab-orbent layer The peroxide passes through to react with any h -oglobin present in the speci~en, and in a positive t st, the guaiac in the absorbent layer is converted to a blue color Th eolor is conveniently observed, free o* interference by th opagu , ~- colored speci~en, on the sa~e underside of the absorbont layer This form of the te~t ha~ a nu~bQr of defect- and thoy have been ~et by a series of nodification- and i4prove~ent~
First, guaiac i8 easily oxidized to a blu color on prolonged expo8ure to air Therefor , it ~u-t b- prot-ct d fro~ oxidation in order to prev nt ineorr ct results, and its effectiveness verified at tho ti~e the a--ays aro 35 perfor~ed U S Patent No 4,382,064 to Detwiel-r t al discloses a coating for surfaces in contact with guaiac in the device, the coating comprising the antioxidant BHT
incorporated into a varnioh appll-d to th- ~urfaa-~ U 8 Patent No 4,365,970 to L~ur-ne- t al di~olo--- on-d id-positive and negativ- p-rfor~anee ~onitor~ for the guaiac test wherein the po-itive eontrol eompri~- a h-moglobin component Another defect in the guaiac test for oeeult blood is that it is ub~eet to interf-rence from other oxidative reaction~ in the speci~en which give ri~e to fal-e po~itive results One souree i8 that of peroxida--~ pr ~ent in foods whieh apparently ~urvive the dige~tiv proe-s~ and re~ain aetive in fecal ~aterial U S Pat-nt No ~,333,734 to Fleischer discloses an improved guaiae ehemi-try which comprises inhibitors of co~peting peroxida~es Another i~
that of oxidizing agent- used to olean toilet bowl~ from which the specimens are usually retrieved, and U S Patent No 4,675,160 to Talmage et al discloses test eontrols to detect this source of interference Another problem is that these tests do not provide for reproducible sampling For even qualitative tests to be reliable and significant from te-t to te~t they should be carried out on a defined preferably constant, specimen volume U S Patent 4,273,741 to Levine diseloses a ~ -, -.",, .. , -constant volu e stooI testing devie- wherein the speei~en is applied to a surfaee eontaining an area whieh is a reeessed grid That portion of speeimen r~aining above the grid is ~- ~ removed before the test is performed The eonsequenees of a false positive oecult blood test, indicating colo-rectal bleeding, are seriou~ ine it requires the consideration of more serious im asive ~i 30 diagnostic procedures For this reason, it is eustomary to eonfirm a positive oeeult blood test with a ~ore ~peeifie test for hemoglobin To verify the test rQsults independently, for example, by inmunoassay for bemoglobin, it is often neeessary to ~eeure a ~nple of the fluid phase of the speGimen, substantially uneontaminated by olid material One oecult blood te~ting device provides for a guaiae 2~0058~) test for hemoglobin together with simultaneous ~iampllng of a liquid filtrate of the fecal oipe¢imen. U.8. Patent No.
4,645,743 to Baker disclose~ a fecal te~ting device comprising an absorbent specimen pad having a pocket in which is inserted a second liquid sampling sheet. The specimen pad can be inserted and mounted in a rigid frame which comprises a 6ample receiving sheet impregnated with guaiac. After a fecal specimen is deposited on the absorbent pad, it is placed, specimen side down, in the frame against the receiving sheet. The guaiac test is performed in the conventional way, by applying a few drops of peroxide on the underside of the receiving ~heet. The second sampling layer, the insert, receives a liguid portion of the fecal specimen which has filtered inwardly from the absorbent pad. The insert, containing the liquid sample, can be removed and cut into portions from which the retained liquid can be eluted and assayed by any desired procedure, for example, a radioimmunoassay.
Methods similar to the ~iaker device for follow-up or supplementary testing are unsatisfactory in a number of ways, and can lead to incorrect results.
First, a liguid sample which has been filtered through a volume of an absorbent pad may be less concentrated and it6 composition not representative of the original liquid sample. Absorbent material exerts an initial chromatographic effect on the solutions passing through it, retarding the passage of large molecules with respect to smaller molecules, particularly thiose of water. Unless thie total volume of the liquid in the specimen is sufficient to saturate the pad and thus overcome this effect, the filtered liquid sample will be diluted and its relative composition distorted by the extraction of larger molecules.
The liquid content which will flow from most semi-solid biological specimens is usually quite limited. The effect of collecting a small volume of filtered liquid therefrom through an absorbent pad in almost all cases will be to reduce the sensitivity of any 6ubsequent test, especially ~.~,< ,, :.
2000581~) with respect to the large molecul--Further, unleso the liquld ~a~pl- ¢oll-ct-d on the receiving ourface 1- drain-d from a d-fln-d ~a-pl- volum-and collected in a deflned ar a, th- r-~ult~ of a ~uboegu-nt assay are unreferenced and cannot b compar d over a period of time or from sub~ect to ~ub~-ct Again, the sensitivity of testing cannot bo defined There are other difficulties in attempting to collect a liquid sample from a fecal pecimen in con~unction with a guaiac test In th- use of d-vice~ ~uch a- that of Bak r, the portion of the insert containing the liquid ample muot be cut or punched from the insert, a process which reguir s unsanitary contact ~nother ma~or problem with ~uch devices iB that they must sit for a substantial period of time before they are analyzed Often, this involves transit through the mails, under a wide variety of ambient conditions of temperature and humidity Sticking together of parts of the collection device is a ma~or problem, a6 is drying and possible 108~ of portions of the specimen Such collections also risk the contamination of the liguid sample with wet guaiac indicator diffu~ing from the specimen receiving sheet In addition, the device as `::
disclosed and similar devices are complex and expensive to ~ -fabricate Immunological tests for hemoglobin are presently available in rapid, convenient, easily interpretable colorimetric form quivalent or superior in ~ensitivity to `~ the guaiac test Further, solid-phase ixmunoassays can concentrate analyte from dilute sa ples, thus achi-ving higher sensitivity than colorim tric chemistries Such ,~
`~ tests may be substituted for the guaiac test as a pri ary rather than confir atory proc~dure if there is a means provided to obtain an appropriate liquid or semi-liquid sample from the fecal ~pecimen A1BO~ in an i~ unological te~t for occult blood, ~ust as in the guaiac test, a time ~-lap~e between the collection of the specimen and the " ~-'' ~.,' hemoglobin ao~ay does not aff-ct th- aecuracy of th- r--ult Accordlngly, the de~ign of a f-cal p-cl~-n coll-ctlng devlce for occult blood t-~tlng dlr-ct-d only to th-eollection o~ an appropriat- llquld fraetlon can b fr -d from the reguirem-nts and r -trietion- of th- guaiae chemistry Devices whieh ean eoll-et f-eal apocimen~ for analy~i~
wlthout commitment to a deflned chemistry can also be u~-d to collect any semi-solid ~peciaen in an analogou~ way lo Such peci~ens can be blood clot-, vo~itu-, ~putum, pu-, or olid tissue The collect-d materlal can then b-conveniently eluted and analyzed for a vari-ty of ubstance-according to appropriate analytical proc-dur ~, rath-r than restricted to an 1~ sJtu colorimetric chemical analysi~
It is therefore an ob~ect of the invontion to provide a device capable of collectlng a liquld or ~emi--olid specimen and providing for convenient sampllng therefrom Another ob~ect is to provide a conv ni-nt, ~anitary, folding sample devic- that can b ~hipp d through the mall or stored for a period of time with gr atly reduced drylng and sticking problems It is further an ob~ect of the invention to provide a device capable of collecting a sample of liquid fro~ a se~i-soli~d specimen wherein tho sample accurately r pr -ents tho native composition of the liguid It i8 also an ob~ect of the invention to provide a ~ ~device capable of eollecting a representatiY sa pl- fro~ a -~` defined volume of the sp~cimen It is further an ob~ect of the invention to provide a i 30 device which allows for the sanitary and conv ni~nt re oYal -~ ~ of a sa~plo of the thu~-collect d ~p cimen- to a -parate t-st device It is further an ob~oct of the invention to proYide a procedure whereby a saaple collectod fro a focal pecimen in the device of the invention is thon analyzed for hemoglobin by a solid-phase enzy e iD unoassay, and this procedure is a screoning te~t for oceult blood , . , It i8 further an ob~-et of the lnventlon to provlde a deviee eapable of eonveniently eolleetlng a repre~entatlvo sample from a llquld or ~-ml-~olld ~p-el~-n, whleh d-vie-ean be easily and in-xpen~lv-ly fabrieat-d from a unltary blank SU~ARY oF~
The device of the preoent lnventlon provide~ a ~eans to collect a sample of a se~l-~olld ~p el~en, a llguld or a sample of the liquid eomponent of a eml-solld ~peelmen Preferably, the speel~ n 1~ a blologleal p elmen The device also provides a means to r move the eollected sample from the device by means of an integral detachable transferring stick The detaehable strip has an integral lS handle which i8 used to remove it, together with the eollected sample, from the device A collected sample is eluted from the detachable strip by a volume of solvent, and sample~ of this volume ean then be analyzed, both by gualitative and guantitative ~eans According to one aspeet of the invention there is provided a system for use in the eolleetion of a sample used in the analysis of a liquid or ~emi-~olid speei~en, eomprising a sampling folder having a front panel, a back panel, and a specimen reeeiving portion eovered by the front panel, the two panels being in overlylng relationship to one another, and the front panel b ing openable to permit applieation of a speei~en to the p-eimen r eeiving portion An area of this ~pecimen reeeiving portion comprises material onto which a ~peeinen ean be applied, and whieh is 0 eapable of retaining the speei~en In a preferred embodiment, the speei~en i- a biologieal peei~en The speeimen receiving portion eomprises, at least in part, a detachable sample transferring stick having a handle portion and a sample collecting portlon In one obodiment, the sample transferring stiek is a part of the back panel In another embodiment, the sample transferring ~tiek i8 attaehed to the inside of the back panel According to 2~0058~
another embodiment of thi~ a-pect of th- lnvention, a central leaflet between th- tront and back pan-l~ compri~
the ~peci~en rec-lvlng portlon In thl- mbodl~ nt, th-sa~ple transrerring tlck may comprl~- a part of th- c-ntral 5 leaflet In another bodi~ nt, the tran-f-rr~ng ~tlck 1-attached to the back of th c-ntral l-afl-t In a partlcularly preferred e bodl~ nt, the c-ntral l-aflet is a bilayer of two panels, wher in one of th- pan-ls comprises the specimen r ceiving portion and th- other co prises th-10 sample collecting portion The ~pecimen r-c-iving portion of th- ~ampling d-vice ~ay compri-e, at least in part, a heet of porou- ~aterial, in front of the speciJ n appllcation ar-a to which th-specimen can be applied, wherein the porous material is 15 adapted to permit only a portion of th- specimen to be transferred through the porous ~aterial onto the speci~en - receiving portion In on- embodi~ent of th- inv-ntion, wherein the specimen is g nerally opaque, the ~peci~ n application area includes indicia thereupon which r main 20 visible only when a predeter~ined a~ount of specl~en of less than that amount has b en applied ther to ~o that a us-r can determine that the a~ount of speci~ n appli-d does not ~ exceed the predetermined a~ount -~ In a particularly advantag ous e~bodl~ent, the specl~en 25 recelving portion is porous ~at-rial that has been coated with a release agent to pr vent sticking of the specinen to the porous ~aterial and to prevent sticking tog ther of the - various layers of the sa~pllng devlce In yet another embodl~ent of the lnvention, th back 30 panel includesi-a ~eans for providing a opening through which the sample transf rring stlck can b r noved -`~ In a partlcularly pref rr d bodivent, th pan l~ and th- stick of the inv-ntion ar for~-d fro~ cellulo~ic ~aterial The 6ample collecting portion of the tran~iferring 35 stick ~ay also have an additional layer of ab-orbent ~aterial thereon According to another aspect of the invention, there is ,. , , " . , .
2~00586) :
provided a sampling device a~ part of a kit whleh further comprl-e- a aixing eup; a liguid for u-- ln th- aixing cup to xtract the ~ampl- fro~ aid ~ampl- coll-etlng portion7 and a assay devie- for d-t-r~ining th- pr-~-ne- or guantlty s of an analyt- in th- extr~et-d ~ampl- In a pref rred embodiment, the speei~en i~ a ~tool ~aaple and the analyt-i8 hemoglobin In yet another bodiaent of thi~ aspeet of the invention, the a~ay d-viee in fora of a kit includes a receptacle for holding the eup The eup aay be built into 10 the device According to yet another aspect of the --invention, there i~ provid-d a thod for eoll-eting and ~-analyzing a specimen compri6ing the ~tep- Or opening the front panel of the sampling folder applying a ~peei~en to the specimen application area of the peci~en reeeiving portion elosing the front panel; and thereafter removing the sample transferring stick by gra-ping only the handle ;~ portion thereof, 80 that contact betw n a u~er and a ~ample iB avoided during the ample re~oving t-p and analyzing - the sample on the sample collecting portion of the removed stick for the pre~enc- of an analyt- In a pref-rr d embodiment, the specimen is a stool peeiaen and th analyt-is hemoglobin In a partieularly pr f rr-d ~ bodiaent, tho analyzing step eompris-s an i~ unoa~say In a partieularly preferred embodiment the ~ampling d-viee in th eontext of a 2s kit is a sampling deviee in whieh the speei~ n reeeiving portion comprises at least in part a heet of eoated or non-eoat-d porous material in front of a peei en applieation ;
ar a to which the pecia n ean be applied, wh-rein th-~ porous material i8 adapted to per it only a pred t r in d --i 30; amount of the speci~ n to be transf rr d to the porous aat-rial onto said specim n r eeiving portion Th eoating ~at-rial i~ pr ferably a rel-a-e agent that pr ~ nt- dri d sample from stieking to the porou- aat rial in pref~r nee to the specimen receiving portion -BRIEF DESCRIPTION OF THE DRA~N~-s ~ -Figure 1 is a front vi-w of a pr ferred e bodl~ent of -~
. ~.
' -~' 200(~58~
the folded sampling device Figure 2 i8 a back view Or th- ~old-d ~mpllng d-vlc-Figure 3 is a p-rspective vi-w Or th- a~pllng devic-with the front cover lifted, xpo~ing th- xt-rlor ~urface of the specimen application panel Figure 4 is a perspective view Or the s~pling device with the openable flap Or the back end lirted, xposing the exterior surface of the liquid sample collecting panel Figure 5 is a planar view Or the fac- ~ur~ace Or the unitary blank from which th- sampling dev$c- i~ tolded Figure 6 i~ a planar vi-w of tho r-verse ur~ace o~ the unitary blank from which the sampling device is folded DETAILED DESCRIPTION OF TNE INVENTION
The sampling device 2, according to a preferred embodiment illustrated in Figures 1 through 6, contains a sampling bilayer 48 ncloo-d as a central leafl-t between a iront panel 10 and a back panel 12 The sampling bilayer 48 consists of a specimen receiving panel 14 and a sample collecting panel 16 The front surface of the folded sampling device 2, as best seen in Figure 1, is made up of the front panel 10 which is folded down over the exterior surface of the specimen receiving panel 14 The front cover 10 is held in place by the insertion of its lower edge into a semi-circular slit 22 cut into the specimen receiving ~ panel 14 ;~ The front panel 10 has on its face surface 6 printed matter which may include title~ and trademark, and indicated areas for recording infor ation The back surrace of the folded sampling device 2, as best seen in Figur 2, is the back panel 12 The back panel 12 has an openable flap 18 `~ which i~ defined by an open slit 26, perforated ide edges 28 and a fold line 29 in the area proximal to the kack panel In the folded sampling device 2, the specim n receiving panel 14 and the sample collecting panel 16, lie with their reverse surfaces 8 together to form a bilayer central s~- - .. ... ; ............................................................ :
2~00580 leaflet 48 The ~pecimen receiving panel 14, a~ b-~t ~--n ln Flgur-3, iB expo~ed by lifting the front pan-l 10 m e ~pecimen receiving panel 14, in addition to th- -mi-eireular slit 22 has a pair of punched-out open specimen applie~tion area~ 20 located in the upper half of the panel The punched-out open specimen application areas 20 are filled by a porous screen 30 attached to the reverse urface 8 a~ best seen in Figure 6 The sample collecting panel 16, ~a best seen in Figur-4, is exposed by lifting the openable flap 18 of the back panel 12 The sample collecting panel 16 comprises a pair of detachable sample transferring stieks 24 having a tip 36, a ~ample collecting area 38, and an integral handle 40 The sample sticks 24 are defined by perforated or notched edges 32 Porous screen 30 may also be eoated, to reduce the likelihood that the sereen 30 wiil adhere to sample sticks 24, especially in sample collecting area 38, when samples are collected or transferred The device may alternatively comprise a monolayer central leaflet consisting of the speci~en receiving panel 14 enclosed between the front 10 and back 12 panels In this embodiment, the back panel 12 also serves a~ the sample collecting panel 16 and the transferring sticks 24 are integral parts thereof In another embodiment of this type, the back panel 12 may be a solid sheet and the transferring sticks 24 are attached to the interior side thereof 80 as to underlay the open ~ample applieation areas 20 of the specimen receiving panel 14 Alternatively, the eentral 1 30 leaflet may comprise the transferring sticks The ~ampling deviee 2 may be used to eolleet a sa~ple ~- of a liquid or ~e~i-solid speeimen in ither a defined or undefined volume A defined volume of ~ liguid or ~emi-solid speci~en may be eollected, or a liquid sample may be taken from a eolleeted semi-solid speeimen The open speeimen areas 20 provide for sampling a specimen of a defined volume A defined speeimen ,; ' ` - 2~10Q58C) application area i8 defined by th- geometry of the open specimen areas 20. The ~pecimen volume may be defined by filling an open speclmen area 20 with a ~emi-~olld ~poclmen to the depth of the porou~ screen 30. The porou~ screen 30 preferably ie one with large openings: that is a ~creen with a coarse mesh.
The specimen volume which i8 then retalned in the screen and predetermined by the size of the openings and the depth of the porous screen 30 may in this way be transferred through the porous material and onto the speclmen recelvlng portion.
~ he sampllng device 2 may also be used to collect a defined sample volume of seml-solld specimen according to constructions that eliminate the filter screen 30. For example, the specimen receiving area 14 (which may be identically the sample collecting area 16) may be imprinted with graphic symbols or other indicia which become obscured when an adequate amount of an opaque specimen is applied.
A defined volume of a liquid specimen can be sampled by providing an area of defined absorbency, for example in the open specimen applications areas 20, or on the sample collecting portion 16 of the device 2 and applying the specimen thereto.
The device alco provides for obtaining a liquid ~ample from a defined volume of a ~emi-solid specimen. A liquid sample taken from a semi-solid specimen may be used for either a qualitative analysis for the presence of components or a quantitative analysis for the concentration of components. A liquid sample for qualitative analysis may be collected from a relatively small semi-solid specimen through an absorbent filter on the specimen receiving surface or onto an absorbent layer on the sample collecting surface. If the amount of fluid sample that passes through an absorbent filter is large enough to overcome chromatographic effects which alter the concentration of its components, the liquid sample may be analyzed quantitatively. A liquid sample for quantitative analysis ~ .. . . .
. . ~ ~,. . . .
~,,," ~, ~ " "
~,. ~ . -, , ~-. :, ,,. . - -2~0058~1 may be collected from ven a relatively ~mall amount of ~pecimen by u~ing a form of th- a-ple d-vice havlng no absorbent filter or collectlng urfae-~ Th- ~ample thu~
collected accurately repr-~ent~ the concentration and composition of the liguid pre~ent in the native specimen, in that it retains higher molecular weight ~pecies which are freguently lost due to chromatographic effects in low volume filtrations Liguid i6 drained from a volume of semi-~olid specimen defined by the geometry of a collection space The liguid drains through a filtering screen of non-absorbing porous material, and onto the liguid coll-eting urface of a detachable strip The drained ~pecimen is retained on th-filter 6creen by adherence thereto and by self-adherence and viscosity A liquid sample is collected from a semi-solid specimen in the device 2 by opening the front panel 10 to expose the pecimen receiving panel 14, and applying the specimen to the open specimen areas 20 at a uniform depth to fill the filter screen 30 within, using an imple~ent such as a 6patula, flat stick or 6mall spoon Excess specimen is wiped from all areas of tho specimen receiving panel 1~
except the open specimen areas 20 After the specimen is applied, that area of the liguid sample collecting panel 16 underlying the open speci~en area 20 becomes wetted by liguid seeping through the porou~ filter screen 30 Particles smaller than the pores of the porous filter sereen 30 may also be transferred to the sample collecting panel Modifications of the s~mpling device 2 that provide various degrees of separation of solid and liguid components can be provided by ad~ustments in the porosity of the filter screen 30 In addition, the filter screen 30 ay be coated with a release agent, to deerease the likelihood that sample colIection area 38 of the sample sticks will adhere to the screen The release agent ean be selected from any of various suitable materials Polyhydroxy compounds seem to be ~.
.
2~0058 particularly suitable; however, wator solubl- poly~er~ ~nd fatty materials, such a~ liquid fatty aoid- and triglyceride~, al80 wer- found to be ff-ctlv- Polyhydroxy compounds are well known and an xhaustlv~ t can r adlly be generated by those of klll in th- art Th-~e materlal~
include, but are not limited to, variou~ ~ugar~, lncluding pentoses and hexoses, poly ers of alcohol~, lecithin, alkylene glycols, and the liko While ~ome r lea~e agents functioned more effectlv-ly than oth-r~, almost any (preferably liquid) matorial that can i~prognate and/or coat the fibers of the filter scr en 30 can b~ used to advantage in the invention For example, the following solutions were tested O S%
- 1% polyvinylpyrrolidone (PVP - Calbiochem Corp , La Jolla, 15 CA); 0.25~ - 1% polyethylen~ glycol (PEG - J.T. Bak~r, Jackson, TN) 0 1% - 1% Tween 20 ~Sig~a, St Louis, M0) : ~ PA~ cooking spray (an aerosol of partially hydrogenated vegetable (soy) oil and lecithin, d ~crib d in U S Pat-nt No 4,188,412)(Boyle-Nidway, Inc , NY, NY); and 6 25% - 100%
sucrose (Sigma, St Louis, M0) The coated screens were compared with non-coated filt-r screen in preventing ~ticking of the scrQen to the ~ample collecting portion 16 i~mediately and ~5 minutes after mearing fecal samples The filter screens coated with 0 5%
25PEG, 0 25% PEG, 1% PEG, 1% PVP, 12 5% sucrose and PAM!
:
appeared to be better at preventing stickiness th~n the non-coated filter screen The best solutions for prev nting stickines6 were 0 5% PEG and PAM!, but PAM~ was difficult to work with The Tween 20 ~olutions ~ignificantly incr ased the stickiness of the filter ~cre-ns compared with non-coated screens ; We also tQsted the ffocts of 0 5% PEG and 12 5%
sucrose for interference, ~ensitivity and ~tability in running a hemoglobin (Hb) test Several non-coat-d, 12 5%
sucrose, and 0 5% PEG coated filter screens fecal ~ ple packets were smeared with either a negative fecal ~u~pl- or a spiked fecal sample (2mg Hb/g sample) Three packets from 2~00580 :, `
;.
each group were allowed to dry ~or 45 ~inute~, 24 hour~, and on- week, respectiv-ly, berore t-~ting Th-y w r- lther kept at 4 C, room te~p-rature, 37 C, or ~5 'C Upon running the Hb test on th- pack-t~, O S% PEG and 12 5% ~uero~- did not interfere wlth th- t-~t Ther- w r- no fal~- po-itlve~
or false negatives, and th-y appear d to be ~u~t a~
sensitive as the packets tested with non-eoated filter screen stored at the sa~e te~peratur-The sampling device 2 ~ay aloo b u~-d to eollect an undefined sample volume of intact ~peei~-n, wh-ther liguid or semi-solid, according to o bodi~ nt~ that li~inat- th-filter screen 30 In these e bodi~ nt-, the ~p ci~en ~ay be sampled by direct application to th- a~pl- eoll-eting portion 16 of the device or peeifieally to the ~a~ple area 38 of the transferring stieks 24 in any of th-ir various attachments This may be done aeeording to several arrangements First, the devie ay be ade up with the bilayer 48 eentral leaflet of th pr f rr d bodi~ent, but without the filter sereen 30 In thi- eonfiguration, the speei~en ean be applied directly to th- ~a~pl- eoll-eting portion 16 through the open speeinen applieation areas 20 Secondly, the device ~ay be anufaetured with a ~onolayer central leaflet coaprising identically the sp ci~en receiving portion 14 and the ~a~ple collecting portion 16, and the specimen applied direetly th reon Alternatively, ~, ........................................................................ .
the device may be ~anufactured without a central l-aflet, whorein the inner surface of the back panel 12 ay ~-rve as -the specimen receiving portion 14 or th e~ ple eoll-eting portion 16 i 30 Other arrange~ents can be developed that eonfor~
; to the general requirQ~ents of th inv ntion, and retain th f-atures of the preferred o bodi~ent The sampling device 2 uay bo anufactur d fro~ variou~
~aterials, such a cellulosic, paper or eardboard toek, ;~
plastie or plastic eoated e-lluloie ~aterials, or nitrocellulose, provided any sueh stoek has nough rigidity ~
to maintain the shape of the funetional feature~ The ~--. ~,:
2~100580 material for the filter screen 30 ~hould b- non-absorbent or have a mlnimal absorbency Th- mat-rlal u--d for the fllt-r o¢r-en 30 1B of a uniform thlckne~ ~o that together with the fixed open spe¢imen area~ 20, it d-fln-- a pecimen volume when lt 18 in plac- in th- ~p-¢im n application panel 14 In order to do this it should also have ~ufficient structural rigidity BO that it retains a stable porosity when compressed by a ~pecimen load In a preferred embodiment, the filter screen 30 i8 of nylon mesh, and 1B
preferably coated with a release agent The material used for the ~ampl- tran~ferring ~tick~ 24 need not be either absorbent or porous Self-adherent biological specimens, for example, particularly those that are proteinaceous adhere to the surface of the transferring sticks 24 The liquid volumes which are collected on the sticks 24 is small in most applications and can adhere to the collecting surface by capillary action or as a moisture film The liquid collecting capacity of the tran~ferrinq sticks 24 can be conveniently expanded, when reguired, by an added layer of absorbent material on the surface of the liquid sample transferring sticks 24 The added layer Day be a sheet of filter paper or particles of bibulous material, for example, cellulose flake~ or dry Sepharose beads `~ 25 After the specimen is coll-cted, the lower flap of the front panel 10 is inserted in the semi-circular ~lit 22 of the specimen receiving panel 14 BO as to close the sa pling device 2 The enclosed specimen may now be stored or transported in the device The period the peci~en can remain in the device and the conditions of torage are determined according to the stability of the analyte The sampling device 2 can ultimately b- conveniently discarded The collected samplQ i~ re-oved from the device 2 for analysis by maans of the transferring sticks 24 To remove the sample according to the device of the preferred embodiment, one of the transferring sticks 24 int gral to the sample collecting panel 16 is removed by means of an ., handle 40 provided by lts di~tal nd Th- tran~if-rrlng ~tlcks 24 are loo~ely held ln th- ampl- coll-ctlng panel 16 by attachments at the tip 36 and at polnt- along th-perfor~ted edge~ 32 These attach ent~ ar- a-lly torn by a S ~light pull on the handle 40 Thus, when the tran~ferring stick 24 is grasped at its handlo 40, it can be pulled free from the device 2 In other embodiments, wherein the transferring sticks 24 are attached to the interior side of the back panel 12 by an adhesive substance, they may be similarly pulled free The sample collecting area 38 Or th tran~ferring tick 24 retains a sample of either the intact ~pecimen, which may contain solid particles, an intact liquid ~pecimen, or a sample of liquid which has been drained from a semi-solid specimen The sample is eluted from the transferring stick 24 by a volume of aquieous solution A sample which has been collected on the sample transferring stick 24 can be eluted for the deter ination of - an analyte therein, or an analysis, for example a colorimetric determination, may be performed directly on the stick 24 In a preferred embodiment of the invention, co~prising a companion immunoa~say procedure a8 described b low, any solid particles present in the sample are filtered from the solution in the course of the assay procedure The sampling device 2 is conveniently incorporated into a kit, which also comprises ~aiterials and reagents for determining a particular analyte together with an elution cup or vessel which is conveniently used to transfer a collected liquid sample from the transferring sticks 24 of the sampling device 2 into a ~easured volume of liquid The elution liquid may also be provided a8 a component of the kit In a preferred embodiment, the sampling device 2 is a component in a kit which provides a solid-phage enzy~e immunoassay device together with accessory reagents for the immunological determination of hemoglobin Two such devices k'~
~ 00580 are de~cribed in U 8 Pat-nt Applleatlon- 8-r~al No~
909,020 and 189,049 ar- eonv-nl-ntly adapt-d to th-determlnation of hemoglobln ln a llquld ~a~pl- Th-~-devices eo~prises a porou~ ue~bran- whleh ~ay have antlbody to hemoglobin bound to its upp r ~urfaee and whieh is flxed in a rigid housing Absorbent aterial below the ~embrano acts to wick liquid away from the ~a~ple Any of the samplQ states dlseus~ed above, that 1~, a solid specimen or liquid drained fro~ th- ~p ci~en, ay be analyzed for hemoglobin accordlng to th- proe-dur A oolld sa~ple of the fecal ~peci~en carri-d on the transferrlng tick is eluted using about 200 ~ierolit-r~ of elution volume in the cup provided A portion of the luted e~i-solid or liquid sample is then introdueed into the assay deviee through a prefilter, which re-oves any particulate ~atter, and then onto the surfae- of th- ~e~brane Any hemoglobin present in the sample 18 bound by the antl-~ he~oglobin antibodiQs of th ~embran , whlle unbound ;~ ~ubstances pass through the ~e~bran~ The he~oglobin ~olecules thus bound to the ~urfaee of the ~ brane are then contacted with a volume of solutlon eontainlng Qnsyse-labeled anti-he~oglobin antibodies and are bound also by these Alternatively, the he~oglobin ~olecule ~ay be bound initially by labelQd anti-he~oglobin antibodiQs present in the elution liquid When th enzyme thus bound to he~oglobin i8 allowed to react with a chro~ogenic substrate, -~ the presence of color indicatQs the presencQ of he~oglobin :~:
Control arQas of the ~e brane are preparQd with approprlate reagents to bind the d tecting antibodies in the absene~ of hemoglobin (positive eontrol) or to bind neither these antibodies nor the hemoglobin (n gatlvo eontrol) Aeeording to the pr~ferred bodi~ent, the sa~pling device 2 is for~ed fro~ a unitary blank 4 as best -en in Figures 5 and 6 and having a faeQ surfae- 6 (Figure 5) and a rQvQrsQ surfacQ 8 (Figure 6) The blank co~pri-~s four panels in sequence a front panel 10, a back panel 12, a speci~en application panel 14 and a liquid samplQ eollecting . ; 2nooss~
panel 16 The ends of ad~oinlng pan-l~ ar uark-d by fold line 42, lying betw -n th- a~pl- eoll~etinq pan-l 16 and the specimen applleation pan-l 14, fold lln- ~4, lylng between the specim n applicatlon pan~ and th- baek pan l S 12, and fold line 46 betw en tho ba¢k pan l 12 and the front panel 10 The face eurfaee 6 of th blank ~ eompri~es thoo-surfaces of the panels that fac- outwardly ln the folded device 2; the reverse surface 8 eomprl~eo thooe ~urfaces of the panels that face lnwardly ln the folded devlee 2 --The sampling device 2 i8 ror~ed by foldlng from the unitary blank 4 The 8ampl- eollecting pan l 16 i8 folded back along fold line 42 and against th- epoeim n application - panel 14 with their reverse urfaces 8 togeth r, o that th-sample transferring sticks 24 underlie the specimen lS application area 20 The back panel 12 io then folded along fold line 44 80 that its rever~e surrace 8 io in contaet ;~ with the face ~urface 6 of the oample eoll-etion panel 16 ~ --The front panel 10 is then folded along fold line 46 80 that its reverse surfaee 8 is in eontact with th- face surfac- 6 ~-of the specimen application panel 14 In thi- way, the ~; ~ sp~cimen applieation panel 14 and th a ple eolleetion panel 16 forn a sampling bilayer e ntral l<afl~t ~8 betw on the back panel 12 and the front panel 10 The sampling device 2 ay be used to coll-et samples froa a vari-ty of liquid or ~e~i-solid ~p eimens such as foods, soils, manufaeturing wastes, or pref-rably biologieal samples Appropriate eemi-solid biologieal speeimens are blood elots, sputum, ~UCOU8, pU~, vouitus, ~- gastrie content6, wound debris, gross tissu fro~ urgieal -~
30 `epecimens or biopsi-s, or fecal atter ~-The collected liquid or ~emi-solid a pl- ay be u- d to determine any substanc or ntity ther in, any inorganie or organic chemical ~peei-e, biological mol-eul-s uch a- -enzymes, proteins, lipids or earbohydrates, inf etious -agents such as viruses, bacteria or parasites, eell typ~s present in the speei~ n, or toxins ~any other ob~eets, features, and advantages of th~
: . .
2~t0(~580 present inventlon will be apparont to thos~ Or ~klll in the ~,~
art Although the inv-ntlon has been d-~¢ribed in tor~ of certain preferred embodiment~i, it will b- under~itood that the invention i8 intended only to be li~ited by the lawful scope of the claims that follow, ~nd eqjuival-nts thereor . j .
Claims (27)
1. A system for use in the collection of a specimen, comprising:
a sampling folder having a front panel, a back panel, and a specimen receiving portion covered by said front panel, said panels being in overlying relationship, said front panel being openable to permit application of a specimen to said specimen receiving portion;
said specimen receiving portion comprising, at least in part, a detachable sample transferring stick having a handle portion and a sample collecting portion, wherein a specimen application area of said specimen receiving portion comprises material onto which a liquid or semi-solid specimen can be applied and which is capable of retaining said specimen.
a sampling folder having a front panel, a back panel, and a specimen receiving portion covered by said front panel, said panels being in overlying relationship, said front panel being openable to permit application of a specimen to said specimen receiving portion;
said specimen receiving portion comprising, at least in part, a detachable sample transferring stick having a handle portion and a sample collecting portion, wherein a specimen application area of said specimen receiving portion comprises material onto which a liquid or semi-solid specimen can be applied and which is capable of retaining said specimen.
2. The system of Claim 1, wherein the specimen is a biological specimen.
3. The system of Claim 1, wherein said sample transferring stick is attached to the inside of said back panel.
4. The system of Claim 1, wherein said sample transferring stick comprises a part of said back panel.
5. The system of Claim 1, wherein said specimen receiving portion comprises a central leaflet between said front and back panels.
6. The system of Claim 5, wherein said sample transferring stick comprises a part of said central leaflet.
7. The system of Claim 5, wherein said sample transferring stick is attached to the back of said central leaflet.
8. The system of Claim 1 or Claim 5, further comprising a sheet of porous material in front of said specimen receiving portion to which said specimen can be applied, wherein said porous material is adapted to permit only a predetermined amount of said specimen to be transferred through said porous material onto said specimen receiving portion.
9. The system of Claim 8, wherein said porous material is coated with a release agent to prevent the porous material from sticking to said specimen receiving portion.
10. The system of Claim 9, wherein said release agent comprises a poly hydroxy compound.
11. The system of Claim 9, wherein said release agent comprises a sugar.
12. The system of Claim 9, wherein said release agent comprises polyethylene glycol.
13. The system of Claim 9, wherein said release agent comprises polyvinylpyrrolidone.
14. The system of Claim 1, wherein said specimen is generally opaque and said specimen application area includes indicia thereon which remain visible when only a predetermined amount of specimen, or less, has been applied thereto, so that a user can determine that the amount of specimen applied does not exceed said predetermined amount.
15. The system of Claim 1, wherein said back panel includes a means for providing an opening therein through which said sample transferring stick can be removed.
16. The system of Claim 1, wherein said panels and said transferring stick are formed from cellulosic material.
17. The system of Claim 1, further comprising a layer of absorbent material on the sample collecting portion of said transferring stick.
18. The system of Claim 1 in the form of a kit, further comprising:
a mixing cup;
a liquid for use in said mixing cup to extract sample from said sample collecting portion; and an assay device for determining the presence or quantity of an analyte in said extracted sample.
a mixing cup;
a liquid for use in said mixing cup to extract sample from said sample collecting portion; and an assay device for determining the presence or quantity of an analyte in said extracted sample.
19. The system of Claim 18, wherein said specimen is a stool sample and said analyte is hemoglobin.
20. The system of Claim 18, wherein said assay device comprises an enzyme immunoassay.
21. The system of Claim 18, wherein said assay device includes a receptacle for holding said cup.
22. The system of Claim 18, wherein said cup is built into said device.
23. A method for collecting and analyzing a specimen, comprising the steps of:
opening the sample collecting folder of Claim 1 by lifting the front panel;
applying a specimen to the specimen application area of the underlying specimen receiving portion;
closing the front panel;
thereafter removing the sample transferring stick by grasping only the handle portion thereof, so that contact between a user and the sample is avoided during the removal step; and analyzing the sample on the sample collecting portion of said removed stick for an analyte.
opening the sample collecting folder of Claim 1 by lifting the front panel;
applying a specimen to the specimen application area of the underlying specimen receiving portion;
closing the front panel;
thereafter removing the sample transferring stick by grasping only the handle portion thereof, so that contact between a user and the sample is avoided during the removal step; and analyzing the sample on the sample collecting portion of said removed stick for an analyte.
24. The method of Claim 23 where said specimen is a biological specimen.
25. The method of Claim 23, wherein said specimen is a stool sample and said analyte is hemoglobin.
26. The method of Claim 23, wherein said analyzing step comprises an immunoassay.
27. The method of Claim 23, wherein said folder is the folder of Claim 8.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25803688A | 1988-10-14 | 1988-10-14 | |
| US258,036 | 1988-10-14 | ||
| US409,003 | 1989-09-21 | ||
| US07/409,003 US5182191A (en) | 1988-10-14 | 1989-09-21 | Occult blood sampling device and assay |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2000580A1 true CA2000580A1 (en) | 1990-04-14 |
Family
ID=26946369
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002000580A Abandoned CA2000580A1 (en) | 1988-10-14 | 1989-10-12 | Occult blood sampling device and assay |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US5182191A (en) |
| AU (1) | AU4497189A (en) |
| CA (1) | CA2000580A1 (en) |
| WO (1) | WO1990003927A1 (en) |
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-
1989
- 1989-09-21 US US07/409,003 patent/US5182191A/en not_active Expired - Fee Related
- 1989-10-06 WO PCT/US1989/004481 patent/WO1990003927A1/en not_active Application Discontinuation
- 1989-10-06 AU AU44971/89A patent/AU4497189A/en not_active Abandoned
- 1989-10-12 CA CA002000580A patent/CA2000580A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1990003927A1 (en) | 1990-04-19 |
| US5182191A (en) | 1993-01-26 |
| AU4497189A (en) | 1990-05-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |