Upon a cartridge for containing a specimen sample for optical analysis

• US 20040101443A1
• Filed: 11/25/2002
• Published: 05/27/2004
• Est. Priority Date: 11/25/2002
• Status: Active Grant

• Current Assignee: Menarini Silicon Biosystems S.P.A
• Original Assignee: Immunivest Corporation
• Inventors: Rao, Galla Chandra, Kagan, Michael, Alden, Tor, Prohaska, Jerry
• Granted Patent: US 7,011,794 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/042 Caps; Plugs
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: G01N 21/11 Filling or emptying of cuvettes
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An improved cartridge for holding a fluid sample with a small volume is disclosed herein. The cartridge has a test chamber and a vestibule through which the test fluids are inserted into the test chamber. Improved grips are flared-out to aid manipulation. The handle portion is reinforced to prevent flexing, and a prefabricated trough along the edge of the land surface prevents introduction of the adhesive into the region for analysis. The cartridge has a stopper having a dual sealing mechanism, which seals the test chamber inlet between the vestibule and the test chamber, and the mouth of the vestibule so that when the stopper is in place, the test chamber is closed to the admission of air or other contaminants. The vestibule is similarly closed against escape of the overflow from the test chamber. The stopper is composed of a single elastomer. An improved locking mechanism has two flexible walls on either side of the handhold that locks into their respective keepers on the cartridge to provide a secure lock. Additionally, an improved method for loading the cartridge allows for an even distribution of magnetically responsive particles contained within a fluid sample to be viewed in an array through the optically clear land surface portion of the cartridge.

Claims

1. An improved method for filling an analytic chamber with liquid by introducing said liquid into said chamber having a volume sufficient to fill said chamber to a level either up to or below a fill line, adding a buffer solution having a density different from the density of said liquid when below said fill line with the combined volume of said liquid and said buffer being sufficient to bring the surface of said combined liquids to said fill line, said test liquid and buffer solution providing a liquid interface within the test chamber with said buffer solution on one side and said liquid at the other end, then displacing said buffer solution during a seating step from the one side of said liquid interface into an overflow reservoir through a seal interface, and excluding air from said test chamber through a second seal to preclude voiding of said overflow reservoir, wherein the improvement comprises:

a. positioning said cartridge vertically;

b. filling said test chamber with a fluid sample containing magnetically responsive particles and magnetically labeled target components within a magnetic field such that said test chamber is completely filled with said sample fluid; and

c. storing said cartridge within said magnetic field for use in an apparatus to perform optical analysis.

2. The improved method of claim 1, wherein said filling in said magnetic field is performed within a receptacle having a pair of magnetic poles to induce said magnetic field.

3. The improved method of claim 2, wherein said filling in said magnetic field comprises:

a. mounting said cartridge onto said receptacle having said pair of magnetic poles in opposing orientation and having a gap formed therebetween; and

b. tapering lower surface of said poles toward said gap so that said magnetic field is applied to said test chamber in such a way as to urge said magnetically responsive particles and said magnetically labeled target components within said test chamber towards a wall of said cartridge.

4. An improved apparatus for filling an analytic chamber with liquid by introducing said liquid into said chamber having a volume sufficient to fill said chamber to a level either up to or below a fill line, adding a buffer solution having a density different from the density of said liquid when below said fill line with the combined volume of said liquid and said buffer being sufficient to bring the surface of said combined liquids to said fill line, said test liquid and buffer solution providing a liquid interface within the test chamber with said buffer solution on one side and said liquid at the other end, then displacing said buffer solution during a seating step from the one side of said liquid interface into an overflow reservoir through a seal interface, and excluding air from said test chamber through a second seal to preclude voiding of said overflow reservoir, wherein the improvement comprises:

a. means for positioning said cartridge vertically;

b. means for filling said test chamber with a fluid sample containing magnetically responsive particles and magnetically labeled target components within a magnetic field such that said test chamber is completely filled with said sample fluid; and

c. means for storing said sealed cartridge within said magnetic field for use in an apparatus to perform optical analysis.

5. An improved apparatus of claim 4, wherein said filling means in said magnetic field is within a receptacle having a pair of magnetic poles to induce said magnetic field.

6. An improved apparatus of claim 4, wherein said filling means in said magnetic field comprises:

a. means for mounting said cartridge onto said receptacle having said pair of magnetic poles in opposing orientation and having a gap formed therebetween; and

b. means for tapering the lower surface of said poles toward said gap so that said magnetic field is applied to said test chamber in such a way as to urge said magnetically responsive particles and said magnetically labeled target components within said test chamber towards a wall of said cartridge.

7. An improved cartridge with a body of non-magnetic inert material adapted to be slidably engaged in a receptacle of an apparatus for performing optical analysis of a fluid sample, said body having a domed cross section with an optically clear flat land portion adapted to be positioned in a field of observation for optical analysis, a test chamber underlying said flat land portion adapted to be filled vertically along a longitudinal axis with said fluid sample, a vestibule above said test chamber adapted to act as an overflow reservoir capable of being sealed both from said test chamber and an exterior environment, and an inlet between said test chamber and said vestibule, wherein the improvement comprises:

a. a handle portion flanked by a grip area made to flare outwardly from respective top edges of said handle;

b. said handle having an arch-like extension on a first face, said first face located on said domed side of said body, said arch-like extension running along an uppermost portion of said handle and spanning between said flared-out edges of said grip area and a second face having an inner framed structure bounded along a radial axis by two keeper elements and along a longitudinal axis by said uppermost portion and by an enlarged mouth of said vestibule, said second face located on opposite side of said body.

8. An improved cartridge according to claim 7 comprising a translucent plastic chamber as said body wherein the improvement.

9. An improved cartridge according to claim 7 comprising said body selected from the group consisting of polycarbonate, polystyrene, and acrylic.

10. An improved cartridge according to claim 9 consisting of no fluorescent additives.

12. A stopper according to claim 8 wherein said elastomer has a durometer value in the range of approximately 60 to 100.

13. A stopper according to claim 8 wherein said elastomer has a durometer value in the range of approximately 80 to 90.

14. A stopper according to claim 8 wherein said elastomer has a durometer value of about 90.

11. An improved stopper having a probe on a projecting stem of said stopper, said probe forming first seal adapted to sealingly seat in said inlet and close the same, said first seal precluding air entrapment within said test chamber upon being seated in said inlet, said probe having a distal end adapted to enter said inlet of said test chamber below an established fill level before said first seal closes said inlet, said distal end having a thickness sufficient to displace liquid upwardly through said inlet and position the surface of said fluid sample in said vestibule prior to said first seal closing said inlet and a plug on said projecting stem of said stopper proximal to said probe, said plug having a position along said projecting stem such that said vestibule remains open to said environment until after closing of said inlet by said probe then said plug engages with an enlarged mouth on said vestibule effecting a second seal to close upper end of vestibule, wherein the improvement comprises:

a. a single elastomer; and

b. a locking mechanism to engage with said keeper elements on said cartridge, said mechanism having flexible walls on each side of stopper handhold such that when said second seal closes the vestibule said flexible walls are compressed until they snap outwardly and allow said stopper to lock into place.

15. A process for the manufacture of a cartridge having an optically clear land surface affixed to a plastic body, the process comprising:

(a) molding a plastic edge so as to be in contact with said optically clear land surface such that said plastic edge is shaped as a small shelf for seating outer portion of said land surface,

(b) shaping the entire contact area of said small shelf into a small trough such that said small trough runs along said outer portion of land surface,

(c) filling said small trough with an optically clear adhesive along entire said contact area,

(d) placing said outer portion of land surface on said small trough such that said adhesive is allowed to wick down said small trough and away from all possible optical paths, and

(e) exposing said adhesive to UV light such that said optically clear land surface becomes affixed to said plastic edge.

16. A process according to claim 15 wherein said optically clear adhesive is a non-fluorescent compound which binds after exposure to UV light.

17. A process according to claim 15 wherein said optically clear adhesive is selected from the group consisting of pressure-sensitive adhesives, heat cured adhesives, and adhesives activated by ultraviolet light.

18. A process according to claim 15 wherein said optically clear adhesive is an adhesive activated by ultraviolet light

19. A process according to claim 15 wherein said optically clear land surface is glass.

20. A process according to claim 17 wherein said glass is cut to tight tolerances at around 0.5 mm thick ×

31 mm in length and 5 mm in width.