U.S. patent application number 10/796856 was filed with the patent office on 2004-09-02 for method and apparatus for performing microassays.
This patent application is currently assigned to Massachusetts Institute of Technology. Invention is credited to Hunter, Ian W..
Application Number | 20040171166 10/796856 |
Document ID | / |
Family ID | 22099761 |
Filed Date | 2004-09-02 |
United States Patent
Application |
20040171166 |
Kind Code |
A1 |
Hunter, Ian W. |
September 2, 2004 |
Method and apparatus for performing microassays
Abstract
A method and apparatus for analyzing a plurality of substances.
A platen is provided having two substantially parallel planar
surfaces and a plurality of through-holes. An optical arrangement
analyzes light emanating from the through-holes. The through-holes
may be individually addressable, and may have volumes less than 100
nanoliters. Samples may be accurately dispensed, diluted and mixed
in accordance with embodiments of the invention, and may be plated
onto walls of the through-holes, and then subsequently resuspended
prior to characterization, or, alternatively, retained in the
through-holes by surface tension.
Inventors: |
Hunter, Ian W.; (Lincoln,
MA) |
Correspondence
Address: |
BROMBERG & SUNSTEIN LLP
125 SUMMER STREET
BOSTON
MA
02110-1618
US
|
Assignee: |
Massachusetts Institute of
Technology
Cambridge
MA
|
Family ID: |
22099761 |
Appl. No.: |
10/796856 |
Filed: |
March 9, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10796856 |
Mar 9, 2004 |
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09710082 |
Nov 10, 2000 |
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6743633 |
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09710082 |
Nov 10, 2000 |
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09225583 |
Jan 5, 1999 |
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6387331 |
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60071179 |
Jan 12, 1998 |
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Current U.S.
Class: |
436/164 ;
436/174 |
Current CPC
Class: |
C12Q 1/34 20130101; C40B
70/00 20130101; B01L 3/5085 20130101; B01F 33/30351 20220101; B01J
2219/00351 20130101; Y10T 436/11 20150115; B01F 33/3021 20220101;
B01J 2219/00549 20130101; B01J 2219/00533 20130101; G01N 35/00069
20130101; G01N 35/1002 20130101; B01J 2219/00317 20130101; C40B
60/14 20130101; B01J 2219/00536 20130101; G01N 21/75 20130101; B01J
2219/00599 20130101; B01L 2200/0642 20130101; G01N 2035/00237
20130101; Y10T 436/112499 20150115; B01L 3/50857 20130101; B01J
2219/00585 20130101; B01J 2219/00313 20130101; B01L 3/5025
20130101; B01J 19/0046 20130101; Y10T 436/25 20150115 |
Class at
Publication: |
436/164 ;
436/174 |
International
Class: |
G01N 021/00 |
Claims
I claim:
1. A method for analyzing specified properties of a set of
substances, the method comprising: a. providing a platen having two
substantially parallel planar surfaces, an inner layer of
hydrophilic material and two outer layers of hydrophobic material
coupled to opposite sides of the inner layer, and a two-dimensional
array of addressable through-holes having an areal density of at
least 1.6 through-holes per square millimeter, b. retaining a set
of distinct substances in respective through-holes of the array in
such a manner that a first through-hole contains a first substance
distinct from a second substance contained in an adjacent
through-hole to the first through-hole; c. adding a liquid into at
least one of the through-holes containing a substance for
permitting a reaction between the liquid and the substance; and d.
characterizing contents of distinct through-holes in terms of the
specified properties.
2. A method according to claim 1, wherein the set of different
substances includes a reagent.
3. A method according to claim 1, wherein the set of different
substances comprises a library of at least 1000 substances.
4. A method according to claim 1, wherein the set of different
substances include optical taggants.
5. A method according to claim 1, wherein the step of retaining the
set of distinct substances further includes: loading the set of
distinct substances in one of liquid solution and suspension; and
forming coatings of the distinct substances so as to retain the
distinct substances on walls of the through-holes.
6. A method according to claim 1, wherein the step of adding a
liquid includes adding a liquid substantially uniformly to the
through-holes of the array.
7. A method according to claim 6, wherein the step of adding a
liquid includes resuspending the distinct substances in liquid by
means of wetting.
8. A method according to claim 1, wherein the step of
characterizing contents of distinct through-holes includes
characterizing by optical methods.
9. A method according to claim 8, wherein the step of
characterizing contents of distinct through-holes includes
characterizing by fluorometric methods.
10. A platen for retaining biological samples, the platen
comprising: a. an inner layer of hydrophilic material and two outer
layers of hydrophobic material coupled to opposite sides of the
inner layer; b. a two-dimensional array of addressable
through-holes having an areal density of at least 1.6 through-holes
per square millimeter, c. a set of distinct substances in
respective through-holes of the array.
11. A platen according to claim 10, wherein distinct substances of
the set of distinct substances are coated on walls of the
through-holes.
12. A platen according to claim 10, wherein distinct substances of
the the set of distinct substances are retained within
through-holes of the platen by surface tension.
Description
[0001] This application is a divisional application of copending
application U.S. Ser. No. 09/710,082, filed Nov. 10, 2000, a
divisional application of U.S. Ser. No. 09/225,583, filed Jan. 5,
1999, claiming priority from U.S. Provisional Application No.
60/071,179, filed Jan. 12, 1998, from which application the present
application also claims priority. All of the above applications are
incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention pertains to an apparatus and method
for manipulating, transporting, and analyzing a large number of
microscopic samples of a liquid or of materials including cells
currently or formerly in liquid suspension.
BACKGROUND OF THE INVENTION
[0003] Chemistry on the micro-scale, involving the reaction and
subsequent analysis of quantities of reagents or analytes of order
microliters or smaller, is an increasingly important aspect of the
development of new substances in the pharmaceutical and other
industries. Such reaction and analysis may accommodate vast
libraries containing as many as a million compounds to be reacted
and analyzed under various conditions. Significant problems
associated with current technologies as applied to chemical
analysis of vast numbers (potentially on the order of hundreds of
thousands or millions per day) of compounds include the problem of
handling vast numbers of compounds and reactions in parallel.
[0004] Existing technology relies on 96-, 384-, or 1536-well plates
containing quantities between approximately 1 microliter and 1
milliliter of liquid compound per well, and, generally, involves
chemical reactions and analysis in wells disposed with single
openings on flat, two-dimensional surfaces such as silicon chips.
It is not practical to apply existing technology in the art to form
million-well disks. There is a need, therefore, for new approaches
that permit the analysis of a million samples in a laboratory
format.
SUMMARY OF THE INVENTION
[0005] In accordance with one aspect of the invention, in one of
its embodiments, there is provided a method for selecting samples
having specified properties from a library of samples. The method
has the steps of:
[0006] a. providing a platen having two substantially parallel
planar surfaces and a plurality of addressable through-holes
disposed substantially perpendicularly to the planar surfaces;
[0007] b. loading a first sample in liquid form into at least one
of the through-holes;
[0008] c. adding a second sample into the at least one of the
through-holes for permitting a reaction between the first sample
and the second sample; and
[0009] d. characterizing the reaction in the through-hole in terms
of the specified properties.
[0010] In accordance with alternate embodiments of the invention,
each through-hole may be dimensioned so as to maintain a liquid
sample therein by means of surface tension, and may have a volume
less than 100 nanoliters. The plurality of addressable
through-holes may have a density in excess of 10.sup.8 per square
meter.
[0011] In accordance with further alternate embodiments of the
invention, the step of loading a first sample may include drawing
the sample from a planar surface by capillary action. The platen
may be brought into contact with a reservoir of liquid and rotated
about an axis perpendicular to the surface of the reservoir or
about at least one of an axis perpendicular to the surface of the
reservoir and an axis parallel to the surface of the reservoir. The
method may include the further step of maintaining a humid
atmosphere for preventing evaporation of the first sample or
coating the liquid sample with a monolayer for preventing
evaporation of the first sample.
[0012] In accordance with a further aspect of the present
invention, a method is provided for preparing a plurality of
combinations of members of a first set of samples in liquid form
with members of a second set of samples in liquid form, the method
comprising:
[0013] a. providing a first perforated platen having through-holes
and a second perforated platen having through-holes;
[0014] b. loading a first set of samples in liquid form into the
through-holes of the first perforated platen;
[0015] c. loading a second set of samples in liquid form into the
through-holes of the second perforated platen;
[0016] d. registering the through-holes of the first perforated
platen with the through-holes of the second perforated platen;
and
[0017] e. combining the first set of samples with the second set of
samples.
[0018] In accordance with yet further aspects of the present
invention, there are provided methods for mixing and diluting
liquid samples. The methods have steps of loading one set of liquid
samples into through-holes of a first platen and loading another
set of liquid samples into through-holes of a second platen, and
then disposing a surface of the first platen in contact with a
surface of the second platen in such a way as to register at least
one through-hole of the first platten with at least one of
through-hole of the second platten for permitting mixing of the
liquid samples of the respective sets.
[0019] In accordance with another aspect of the present invention,
there is provided a system for analyzing a plurality of liquid
samples. The system has a platen having two substantially parallel
planar surfaces and a plurality of through-holes having apertures
and walls, a source of optical radiation for illuminating at least
one through-hole along an optical axis, and an optical arrangement
for analyzing light emanating from the at least one
through-hole.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The foregoing features of the invention will be more readily
understood by reference to the following detailed description taken
with the accompanying drawings in which:
[0021] FIG. 1 is a side view in cross-section of a portion of a
laminated platen containing multiple through-holes for analysis of
liquid samples in accordance with a preferred embodiment of the
present invention;
[0022] FIG. 2A is top view of a portion of the platen of FIG. 1 in
which the through-holes are configured on rectangular centers;
[0023] FIG. 2B is top view of a portion of the platen of FIG. 1 in
which the through-holes are configured in a hexagonal close-packed
array;
[0024] FIG. 3 is a top view of round sample wafer populated with
through-holes in accordance with an embodiment of the present
invention;
[0025] FIG. 4 is a side perspective view of an arrangement for
loading a liquid sample into the platen of FIG. 1 by employing
capillary and inertial insertion forces;
[0026] FIG. 5 is a cut-away view of a single through-hole in the
platen of FIG. 1, showing the use of hydrophobic and hydrophilic
layers for containment of an aqueous sample;
[0027] FIG. 6 is schematic diagram of a confocal optical
arrangement for interrogation of a liquid sample in a through-hole
in accordance with an embodiment of the present invention;
[0028] FIG. 7 is perspective view of a scanning arrangement for
serially interrogating liquid samples retained in through-holes of
a disk-type platen in accordance with an embodiment of the present
invention;
[0029] FIG. 8 is schematic representation of a scanning arrangement
for serially interrogating liquid samples retained in a
continuous-process film-type platen, in accordance with an
alternate embodiment of the present invention;
[0030] FIG. 9 is a cross-sectional view of portions of two platens
brought into proximity with through-hole registration in
anticipation of mixing or dilution in accordance with embodiments
of the present invention; and
[0031] FIG. 10 is a cross-sectional view of the portions of two
platens of FIG. 9 after the two platens have been brought into
contact to facilitate mixing or dilution.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0032] Through-Hole Wells
[0033] In accordance with a preferred embodiment of the invention,
the volume of each well employed for the assay of a chemical or
biochemical reaction is reduced typically to less than 100
nanoliters (10.sup.-10 m.sup.3). The packing density of wells may
thereby be increased by several orders of magnitude over prior art
technology. Referring to FIG. 1, a side view is shown in cross
section of a platen 10, otherwise referred to herein as a
"substrate" or "sample wafer." Platen 10 is the carrier of a large
number of through-holes 12 which traverse platen 10 from one
surface 14 to an opposing surface 16 of the platen and constitute
assay wells (or "microwells") in accordance with an embodiment of
the invention. Through-holes 12 may be shaped as circular right
cylinders, or, alternatively, may have rectangular cross-sections,
however otherwise shaped through-holes are within the scope of the
present invention. As used in the present description and in the
appended claims, the term "platen" refers to a structure having
substantially parallel plane surfaces and transverse dimensions
substantially exceeding the thickness of the structure between the
substantially parallel plane surfaces.
[0034] The apertures of through-holes 12 need not be square, and,
in accordance with an alternate embodiment of the present
invention, flanges 8 may extend above planar surface 14 surrounding
some or all of through-holes 12 while indentations 6 may be
fabricated rounding the edges of through-holes 12 at opposing
surface 16. Flanges 8 and indentations 6 may advantageously provide
for registration of successive platens 10, in the case where
platens are stacked, and in processes of mixing or dilution, as
discussed in detail below in reference to FIGS. 9-10.
[0035] In accordance with an embodiment of the invention,
through-holes 12 are loaded with a first sample 18 in liquid form.
Sample 18 is allowed to react with a second sample where the second
sample may include a variety of test samples and by subsequent or
concurrent analysis of the reaction products, using, for example,
optical markers, a large number of reactions may be processed and
analyzed in parallel.
[0036] As applied to biological assays, by way of example, first
sample 18 may be a reagent, including, for example, cells in
aqueous suspension, eukaryotic (animal, yeast) or prokaryotic
(bacteria) cells, hybrid cells, and biological molecules including,
for example, antibodies and enzymes, although application to other
biological or non-biological assays is within the scope of the
invention as claimed herein. All such reagents may also be referred
to herein and in the appended claims as "targets." Typical yeast
cell concentrations of 10.sup.7 cells per milliliter of solution
yield on the order of 1000 cells per 100 nanoliter well. Typically,
an entire chip or the subset of through-hole wells constituting a
contiguous region of platen 10 may be populated with a single
strain of cells.
[0037] A typical procedure assay procedure, such as may be employed
in pharmaceutical research, entails the subsequent addressed
introduction of a test sample including one or more analytes into
the through-hole wells, with selected materials introduced into
subsets of through-holes that may include one or more
through-holes. The test sample addressably introduced into the
subsets of through-holes may contain drug candidates or known
drugs. The test sample may be comprised of multiple components,
introduced at the same time or sequentially. Components of the test
sample may include analytes, antagonists, reagents, solvents, or
any other materials and may be introduced in liquid form or
otherwise. In accordance with a preferred embodiment of the
invention, test samples are introduced into the through-hole wells
in liquid form in order to facilitate rapid reaction via diffusion
with first sample 18 already resident in liquid form in the
through-holes.
[0038] The set of substances from which the second sample addressed
to a particular through-hole site is drawn is referred to in this
description and in the appended claims as a "library" of
substances. In typical applications, the library is of a
substantial size and thus advantageously utilizes the capability of
the present invention to facilitate parallel reaction and analysis
of large numbers of substances. In pharmaceutical applications in
particular, libraries may be composed of between 10.sup.3 and
10.sup.9 substances and combinations of substances.
[0039] A typical thickness 20 of platen 10 is on the order of 1-2
mm, while through-holes 12 have typical characteristic dimensions
(such as diameters) 22 of on the order of 100-400 .mu.m. Thus the
volume of each through-hole 12 between surface 14 and surface 16 is
on the order of .about.10.sup.-7 cm.sup.3 or greater. Through-holes
12 are spaced on centers typically on the order of twice the
diameter of the holes, although all spacing configurations are
within the scope of the invention and of the appended claims. In
particular, through-holes 12 may be centered on a rectangular grid,
as shown in FIG. 2A, or in a close-packed hexagonal lattice, as
shown in FIG. 2B.
[0040] In accordance with an alternate embodiment of the present
invention described with reference to FIG. 3, through-holes 12 may
be disposed in an array within a circular sample wafer 300 having a
central hole 302 for purposes of centering with respect to handling
equipment.
[0041] Referring again to FIG. 1, platen 10 may be any solid or
quasi-solid material into which through-holes 12 may be formed. In
particular, in accordance with various embodiments of the
invention, platen 10 may be formed from metal, semiconductor,
glass, quartz, ceramic or polymer materials, all given without
limitation by way of example. In accordance with a preferred
embodiment of the invention, platen 10 is formed in a format
associated with a compact disk read-only-memory (CD-ROM)-namely
that of a polymer disk, approximately 1.2 mm in thickness, and
approximately 100 mm in diameter.
[0042] Platen 10 may also advantageously be formed of a laminate of
materials, with a central layer 26 and outer "sandwiching" layers
28. Advantages of this construction for containment of sample 18
will be discussed further below.
[0043] Through-holes 12 may be formed in platen 10 by means
appropriate to the material of platen 10. Through-hole forming
methods include, by way of example, laser ablation by means of an
ultraviolet (UV) excimer laser which may form 100 .mu.m
through-holes in glasses and polymers. Additional through-hole
forming techniques include mechanical drilling, electrochemical
methods, or selective chemical or charged-particle etching
techniques. Additionally, microcapillary bundles of glass fibers of
varying compositions may be drawn from preform and sliced to form
platens, and then selectively etched to form through-holes.
[0044] Loading the Through-Hole Microwells
[0045] On the size scale employed in accordance with embodiments of
the invention, where through-holes 12 have aspect ratios of axial
length to diameter greater than unity, viscous forces may dominate
inertial forces in governing the fluid kinetics of material in the
through-hole wells. Consequently, capillary action may be employed
to populate through-holes 12 with sample fluid 18. Referring to
FIG. 4, two aspects of loading the through-hole wells are described
with reference to a sample insertion apparatus 30. Since
through-hole microwells 12 are open at both sides, insertion of
liquid into the wells does not require that the air displaced by
the liquid on insertion flow through the entering fluid, as occurs
in the prior art well structure having only a single aperture for
influx of liquid and efflux of displaced air. Liquid 32, loaded
into reservoir 34 via port 33, may, as discussed above, contain
cells or other particles in suspension. Liquid 32 may be forced
into through-hole microwells 12 (shown in FIG. 1) by in-line
impulsion as by driving platen 10 into liquid 32 by force applied
along direction 36 transverse to the plane of platen 10. The
transverse piston force may be applied via shaft 38 or in any other
manner known in the mechanical arts.
[0046] In accordance with another embodiment of the invention,
liquid may also be loaded through capillary action of liquid 32
along the walls of the through-holes. To provide for wetting of the
lower surface of platen 10, the platen is lowered into reservoir 34
and rotated, by torque applied through shaft 38, or otherwise,
through an angle typically on the order of a quarter revolution.
Alternatively, platen 10 may be wetted and liquid 32 drawn into the
microwells by immersing platen 10 into liquid 32 and tilting the
platen about an axis in the plane of the platen.
[0047] Stabilization with Respect to Capillary and Evaporative
Liquid Loss
[0048] In order to maintain the sample in liquid form in the
respective microwells, evaporation of the liquid must be avoided.
One method of avoiding evaporation is to provide an ambient
atmospheric environment of 100% humidity. Among other methods that
may be practiced to suppress evaporation, in accordance with an
embodiment of the invention, a high molecular-weight fluid, such as
various alcohols, for example, may be introduced on each end of the
microwells thereby forming molecular monolayers or other thin
layers to prevent evaporation of the liquid sample.
[0049] Referring to FIG. 5, a cross-section of a portion of platen
10 is shown to include through-hole microwell 12. In order to
enhance capillary loading of the microwell and to prevent capillary
outmigration of the sample liquid, exterior sections 40 of the
microwell, adjacent to surfaces 14 and 16 of platen 10, has a
hydrophobic wall surface in accordance with a preferred embodiment
of the invention, while the interior section 42 of the through-hole
wall has a hydrophilic surface thereby preferentially attracting an
aqueous liquid sample. Typically, the interior .about.160 .mu.m
segment of the microwell may have a hydrophilic wall surface, while
the hydrophobic layers on either end of the well are on the order
of 20 .mu.m in length. On loading the sample liquid into the
microwells, typically 10% of the well, on either end, is left
unfilled, and subsequent test samples in liquid form will rapidly
diffuse to hydrophilic center of microwell thereby mixing with the
liquid already present.
[0050] Optical Interrogation
[0051] Depending upon the application to which the present
invention is applied, the result of the reaction of the first
sample in liquid form with subsequently added analytes may be read
out in a wide variety of manners known to persons skilled in the
biological or biochemical arts. Readout systems may employ taggants
of various sorts allowing interrogation of the sample within the
addressable microwell to determine whether a specified reaction has
occurred. Some reactions may be interrogated optically, to include,
without limitation, such optical methods as colorimetric or
fluorometric methods, or resonant or non-resonant scattering
methods, including Raman spectroscopic methods.
[0052] Referring now to FIG. 6, optical interrogation methods, of
which the foregoing are but examples, may be implemented, in
accordance with an embodiment of the invention by coupling a light
beam 50 into through-hole 12 of platen 10 and detecting light 52
emergent from the opposite aperture of through-hole 12 by detectors
54 constituting detector array 56. Alternatively, light returned by
scattering in the original direction can be collected and analyzed
using standard optical techniques. In order to optimize the
signal-to-noise of the optical signal, the beam shape and
through-hole volume are preferably matched. In accordance with a
preferred embodiment of the invention, optical matching to a
through-hole of cylindrical cross-section and of aspect ratio
greater than one is achieved through a confocal optical geometry in
which an initially collimated beam 50 is transformed by optical
element 58 into a beam having a diffraction limited focus at the
center 60 of through-hole 12. The emergent optical beam 52 is
collected and focussed onto detector array 56 by optical element
60. Superior optical sampling of the volume of the through-hole may
be obtained if the through-hole has a rectangular cross-section,
and if the optical radiation is guided by the walls of the
through-hole in the manner of a waveguide. Optical element 58 and
60 may be lenses or mirrors or combinations thereof as well known
to persons skilled in the optical arts. Detector array 56 may be a
charge-coupled device (CCD) array, for example, and, in one
embodiment of the invention, a 1000.times.1000 element format is
employed, with each through-hole imaged onto three elements 54 of
the detector array. A window 62 may be disposed between platen 10
and detector array 56 and may be dried using standard techniques if
the assay is conducted in a humid ambient environment as discussed
above. Alternatively, beam 50, coupled into through-hole 12 by
coupling element 58 may be guided, in the manner of a guided wave
through a waveguide, by the walls 62 of through-hole 12 in order to
provide efficient interrogation of the sampled volume within the
through-hole.
[0053] In some cases, where the material of platen 10 is not
entirely opaque at the wavelengths of interrogating optical beam
50, wall 62 of through-hole 12 may be coated to prevent light
leakage and cross-talk among the addressable sample volumes.
[0054] FIG. 7 shows a preferred embodiment of the present invention
in which platen 10 is configured in the CD-ROM format described
above, with interrogating optical source 50 capable of travel in
radial direction 68 while platen 10 rotates about center 66.
Optical detector array 56 may translate in conjunction with source
50, in accordance with an embodiment of the invention.
[0055] Continuous Process Analysis
[0056] Referring to FIG. 8, in accordance with an advantageous
embodiment of the present invention, platen 10, which may be a
flexible polymeric substance, for example, is conveyed in a
direction 70 past an optical interrogation system comprising an
optical source 72 and a detector array 74. Samples in liquid form
may be loaded into through-holes 12 and advanced at a rate governed
by the relevant reaction times so that a row 76 is interrogated
optically at the period during which a specified indication is
expected.
[0057] Mixing and Dilution
[0058] Referring now to FIG. 9, a cross-sectional view is shown of
portions of a first platen 90 and a second platen 92 brought into
proximity with each other in anticipation of processes performed in
accordance with embodiments of the present invention for preparing,
mixing, or diluting liquid samples. Through-holes 12 of platen 90
are shown as having been loaded with liquid samples 94 which may be
identical across some specified subset of through-holes 12, or may
be identical for the entire platen. Liquid sample 94, as shown
schematically, may include cells or other targets 96 in solution
within a solvent 98.
[0059] Through-holes 12 of second platen 92 is shown as having been
loaded with liquid samples 100 and 102 shown comprising one or more
solvents or other agents. In particular, platen 92 may have been
populated with a library of distinct compounds, each of which is to
be exposed to target 96 of platen 90.
[0060] FIG. 10 shows platens 90 and 92 of FIG. 9 having been
brought into contact with one another, in such a manner as to allow
through-holes of the respective platens to register on a one-to-one
basis. The mating of protrusions 8 with indentations 6 of
respective platens facilitates the registration of through-holes,
and provides for the mixing of the liquid sample contents of the
respective through-holes. Thus, as shown, half of targets 96 from
samples 94 of first platen 90 have migrated to the solvent of
samples 100 and 102. Mixing or dilution may be facilitated in this
manner, either through ordinary statistical diffusion, or by any
method employed to facilitate mixing. Mixing may be enhanced, for
example, by the creation of thermal eddy currents and turbulence
induced by laser irradiation. Mixing rates have been found to be
enhanced in this way by more than an order of magnitude. Any other
mixing techniques, including acoustic perturbation or stirring of
the samples with micropipettes, for example, are within the scope
of the present invention as described herein and as claimed in any
appended claims.
[0061] The number of platens 90 and 92 that may be stacked, in
accordance with the present invention, is not limited to two, as
shown in FIGS. 9 and 10 by way of example only. Thus, the
concentration of targets 96 in solvent 98 may be diluted to a
specified degree by stacking a corresponding number of platens with
registered through-holes and allowing migration of targets 96
throughout the liquid contained within the corresponding sample
volumes of the stack.
[0062] Transportation of Biological Samples
[0063] The perforated platen described herein in accordance an
embodiment of the present invention may be employed, for example,
for shipping samples of a uniform strain of cells to laboratories.
In this application, the cells or other biological sample may be
introduced into the through-hole wells of the invention in aqueous
or other liquid suspension. The liquid carrier is then evaporated,
allowing the cells or other biological samples to form a coating,
in the form of a chimney, of the walls of the plurality of
through-hole wells. The samples may then subsequently be
resuspended by wetting and further analytes may be introduced.
[0064] The described embodiments of the invention are intended to
be merely exemplary and numerous variations and modifications will
be apparent to those skilled in the art. All such variations and
modifications are intended to be within the scope of the present
invention as defined in the appended claims.
* * * * *