Multi-well microfiltration apparatus

• US 6,159,368 A
• Filed: 10/29/1998
• Issued: 12/12/2000
• Est. Priority Date: 10/29/1998
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: The Perkin-Elmer Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Jackson, Joseph, Madden, Alfred P., Reed, Mark T., Oldham, Mark F., Hoshizaki, Jon, Bodner, Kevin S., Moring, Stephen E., Halsey, Jason H.
• Primary Examiner(s): FORTUNA, ANA M
• Application Number:
  US09/182,946
• Time in Patent Office: 775 Days
• Field of Search: 210/321.75, 210/474, 210/360.1, 210/258, 210/261, 422/156, 422/101, 422/104, 422/239, 422/258, 435/297.1
• US Class Current: 210/321.75
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• CPC Class Codes: G01N 2035/00485 combined with sample carriers
• CPC Class Codes: G01N 2035/102 Preventing or detecting loss of fluid by dripping
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

The present invention provides multi-well plates and column arrays in which samples (e.g., cell lysates containing nucleic acids of interest, such as RNA) can be analyzed and/or processed. In one embodiment, the microfiltration arrangement is a multilayer structure, including (i) a column plate having an array of minicolumns into which samples can be placed, (ii) a discrete filter element disposed in each minicolumn, (iii) a drip-director plate having a corresponding array of drip directors through which filtrate may egress, and (iv) a receiving-well plate having a corresponding array of receiving wells into which filtrate can flow. The invention provides multi-well microfiltration arrangements that are relatively simple to manufacture and that overcome many of the problems associated with is the prior arrangements relating to (i) cross-contamination due to wicking across a common filter sheet or (ii) individual filter elements entrapping sample constituents within substantial dead volumes. Further, the invention provides multi-well microfiltration arrangements that adequately support discrete filter elements disposed in the wells without creating substantial preferential flow. Additionally, the invention provides multi-well microfiltration arrangements that avoid cross-contamination due to aerosol formation, pendent drops and/or splattering. Other disclosed features of the invention provide for the automated covering or heat-sealing of filtrate samples separately collected in an array of wells.

Claims

1. A microfiltration apparatus for processing a plurality of fluid samples, comprising:

a first plate having a plurality of columns, each column having (i) a first inner bore defining a lumen within the column, and (ii) an end region for receiving a filter medium within the column, said end region defining (a) a second inner bore having a diameter greater than that of the first inner bore and (b) a transition region that joins the second inner bore to the first inner bore;

positioned within each column end region, adjacent said transition region, a filter medium for filtering sample; and

a second plate having a plurality of discharge conduits, each discharge conduit having an upstanding upper end region aligned with and received within a corresponding column end region so as to form a substantially fluid-tight interface therebetween, said discharge conduit upper end region having a terminal rim region for supporting a circumferential region of the filter medium such that each filter medium is held in compression between a column transition region and the terminal rim region of a corresponding discharge conduit in a manner effective (i) to securely hold the filter medium and (ii) to radially press a circumferential side-edge region of the filter medium against an inner sidewall of the column so as to prevent leakage around its edges.

2. The microfiltration apparatus of claim 1, wherein said transition region has an annular tapered portion;

and wherein the circumference of said annular tapered portion decreases in a substantially constant fashion along a direction from said second inner bore to said first inner bore.

3. The microfiltration apparatus of claim 2, wherein a line running along said tapered portion, longitudinally with respect to said column, forms an acute angle with a plane perpendicular to a longitudinal axis of the column and intersecting the column through a junction of said transition region with said second inner bore.

4. The microfiltration apparatus of claim 3, wherein said acute angle is within the range of about 30-60 degrees.

5. The microfiltration apparatus of claim 1, wherein each terminal rim region is in contact with less than about 10% of the surface area of a lower face of a respective filter medium.

6. The microfiltration apparatus of claim 1, further comprising a plurality of fin-like support buttresses positioned in each of said discharge conduits;

wherein said support buttresses have elongated, narrow, uppermost surfaces that are substantially coplanar with a plane defined by said terminal rim region.

7. The microfiltration apparatus of claim 6, wherein the horizontal cross-sectional area of an upper region of each support buttress decreases in a direction extending towards its uppermost surface in a fashion such that the intersection of said uppermost surface with said plane of said terminal rim region is substantially tangential in nature, forming a line.

8. The microfiltration apparatus of claim 1, further comprising

a gas-permeable matrix comprised at least in part of a porous hydrophilic polymer material;

wherein said matrix is attached to said second plate on a face opposite said first plate; and

wherein said matrix circumscribes a plurality of said discharge conduits.

9. The microfiltration apparatus of claim 1, further comprising

means for shifting said first and second plates in either of two directions from a reference "home" position along a generally horizontally extending axis, and then returning said plates back to said reference "home" position;

wherein said shifting means includes a stepper motor in mechanical communication with said plates such that angular rotation of said stepper motor induces linear motion of said plates.

10. The microfiltration apparatus of claim 1, further comprising

means for drawing adherent drops of fluid hanging from said discharge conduits in a direction up into said discharge conduits.