U.S. patent application number 12/796642 was filed with the patent office on 2010-12-09 for microdevice with integrated memory.
This patent application is currently assigned to LIFE TECHNOLOGIES CORPORATION. Invention is credited to Jeffery D. FRAZIER.
Application Number | 20100307921 12/796642 |
Document ID | / |
Family ID | 32108510 |
Filed Date | 2010-12-09 |
United States Patent
Application |
20100307921 |
Kind Code |
A1 |
FRAZIER; Jeffery D. |
December 9, 2010 |
MICRODEVICE WITH INTEGRATED MEMORY
Abstract
The present invention provides microdevices, such as those used
in the pharmaceutical and biotechnological fields, including an
integrated memory. According to various embodiments, the integrated
memory is readable, writable, and rewritable. The present invention
further provides processing stations, e.g., for carrying out
electrophoresis, per, genetic analysis, sample preparation, and/or
sample cleanup, etc., that are capable of reading from and/or
writing/rewriting to such memory.
Inventors: |
FRAZIER; Jeffery D.;
(Portola Valley, CA) |
Correspondence
Address: |
LIFE TECHNOLOGIES CORPORATION;C/O INTELLEVATE
P.O. BOX 52050
MINNEAPOLIS
MN
55402
US
|
Assignee: |
LIFE TECHNOLOGIES
CORPORATION
Carlsbad
CA
|
Family ID: |
32108510 |
Appl. No.: |
12/796642 |
Filed: |
June 8, 2010 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10959746 |
Oct 6, 2004 |
|
|
|
12796642 |
|
|
|
|
10800388 |
Mar 12, 2004 |
|
|
|
10959746 |
|
|
|
|
09955608 |
Sep 19, 2001 |
6726820 |
|
|
10800388 |
|
|
|
|
Current U.S.
Class: |
204/600 |
Current CPC
Class: |
G01N 27/44791
20130101 |
Class at
Publication: |
204/600 |
International
Class: |
G01N 27/447 20060101
G01N027/447 |
Claims
1. A microdevice for electrophoresis of biomolecule-containing
samples, comprising: a substrate; an elongate electroseparation
channel formed in said substrate; a sample-loading region formed in
said substrate, with the sample-loading region being disposed for
fluid communication with said electroseparation channel; and a
rewritable memory integrated into said substrate, with said memory
being adapted for storing binary coded information.
2. The microdevice of claim 1, wherein said sample-loading region
comprises a reservoir formed in said substrate, with the reservoir
being disposed for fluid communication with said electroseparation
channel.
3. The microdevice of claim 1, wherein said sample-loading region
comprises an injection channel formed in said substrate, with the
injection channel being disposed for fluid communication with said
electroseparation channel.
4. The microdevice of claim 1, further comprising: one or more
electrodes, and a power source; with said one or more electrodes
being connectable to said power source, and disposed with respect
to said electroseparation channel for generating an electrical
field along at least a portion thereof.
5. The microdevice of claim 1, wherein said electroseparation
channel includes a cross-sectional dimension of no greater than 500
micrometers.
6. The microdevice of claim 1, wherein said substrate comprises a
plate, wafer, chip, slide, or disc.
7. The microdevice of claim 1, wherein the memory is removably
attached to the substrate.
8. The microdevice of claim 1, wherein the memory is permanently
affixed to the substrate.
9. The device of claim 1, wherein the memory is selected from the
group consisting of integrated circuit memories, optical memories,
thin film semiconductor memories, ferromagnetic memories, molecular
memories, biomolecular memories, and any combination thereof.
10. The microdevice of claim 1, further comprising a
microcontroller chip supported by said substrate and adapted for
communication with said memory.
11. The microdevice of claim 1, further comprising machine-readable
computer code stored in said memory.
12. The microdevice of claim 1, wherein said memory includes a
storage capacity of at least 1 megabyte.
13. A microdevice for manipulation of analyte-containing samples,
comprising: a substrate; an injection channel and a separation
channel formed in said substrate, with said channels intersecting
one another; a reservoir disposed for fluid communication with one
of said ends of said injection channel; and a rewritable memory
integrated into said substrate, with said memory being adapted for
storing binary coded information.
14. The microdevice of claim 13, further comprising: one or more
electrodes, and a power source; with said one or more electrodes
being connectable to said power source, and disposed with respect
to said channels for generating one or more electrical fields along
at least a portion thereof.
15. The microdevice of claim 13, wherein at least one of said
channels includes a cross-sectional dimension of no greater than
500 micrometers.
16. The microdevice of claim 13, wherein said substrate comprises a
plate, wafer, chip, slide, or disc.
17. The microdevice of claim 13, wherein the memory is removably
attached to the substrate.
18. The microdevice of claim 13, wherein the memory is permanently
affixed to the substrate.
19. The device of claim 13, wherein the memory is selected from the
group consisting of integrated circuit memories, optical memories,
thin film semiconductor memories, ferromagnetic memories, molecular
memories, biomolecular memories, and any combination thereof.
20. The microdevice of claim 13, further comprising a
microcontroller chip supported by said substrate and adapted for
communication with said memory.
21-29. (canceled)
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional application of U.S. patent
application Ser. No. 09/955,608, filed Sep. 19, 2001, which is
incorporated herein in its entirety by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to microdevices, such as those
used in the pharmaceutical and biotechnological fields.
BACKGROUND OF THE INVENTION
[0003] In low-throughput situations, sample tracking and record
keeping can often be handled adequately in a manual fashion. For
example, one or several words about a sample, and/or an
alphanumeric identifier, can be written or typed on a label that is
applied to a container holding the sample. In some cases,
additional (e.g., more detailed) information is kept in paper form,
e.g., notebooks, and/or manually entered into a spreadsheet or
database on a computing device, such as a personal computer
(PC).
[0004] With the advent of medium- to high-throughput sample
processing, it has become more challenging to track each sample and
maintain information on it for ready accessing. Providing sample
containers with bar codes has provided some advantages in sample
tracking. As a practical matter, a bar code, per se, carries very
little information, simply being an identifier. Further, there is a
lower limit on the size of container with which a bar code can be
used. In addition, a bar code itself is static information. That
is, once a bar code is written and placed on a sample container, it
cannot be readily changed.
[0005] Sample tracking and information maintenance will become even
more challenging as the industry moves toward microdevice, very
high-throughput formats.
[0006] In an effort to meet the challenges presented by very
high-throughput sample processing, a great deal of effort has been
focused on software and networking solutions to large-scale
information management. It is envisioned that software and
networking technologies will permit instruments and applications of
all types to communicate with one another and to share database
resources for tracking the many, many samples being processed. Many
of today's popular commercial LIMS (laboratory information
management systems), for example, are moving toward the use of open
systems architectures and platforms to offer client/server
capabilities and enterprise-wide access to lab information.
[0007] Notwithstanding the advantages offered by such LIMS, it will
happen that a sample, or many samples in a microdevice, will need
to be physically transported between sites, machines and/or
computers that are not connected by a network or LIMS.
SUMMARY OF THE INVENTION
[0008] Aspects of the invention provide a microdevice including a
memory integrated into the microdevice. The memory can be, for
example, a readable-writable-rewritable memory (also referred to
herein simply as a "rewritable" memory).
[0009] Further aspects of the invention provide a sample-processing
station (e.g., for genetic analysis, electrophoresis, per, sample
preparation and/or sample cleanup, etc.) configured for reading
from, and/or writing/rewriting to, the memory integrated into a
microdevice.
[0010] A wide variety of information can be written to the memory
of a microdevice. For example, sample ID, sample history, sample
lineage, a person's notes pertaining to a sample, etc. In various
embodiments, a memory that is integrated into a substrate defining,
at least in part, a microdevice carries instructions that can be
read by an apparatus for acting on samples held by the microdevice,
which the apparatus can read and carry out. Optionally, the
apparatus can then write to the memory of the microdevice (e.g.,
results pertaining to the act(s) performed, etc.).
[0011] A microdevice of the invention can be transported from one
place to another, and the memory accessed at each location. The
information (written to the integrated memory) and the microdevice
(including any sample(s) therein) can conveniently be transported
and/or stored (etc.) as a unit.
[0012] A microdevice of the present invention can find use alone,
or in combination with one or more other sample tracking and
information storage/retrieval technologies, such as those
previously discussed.
[0013] Among other things, the present invention provides
advancements in methods and devices for tracking samples, and/or
storing and retrieving information pertaining thereto. Such
advancements can be used as an alternative or a supplement to known
methods and devices, such as those previously discussed.
[0014] Aspects of the invention provide a microdevice, various
embodiments of which comprise a substrate or body, such as a plate,
wafer, chip, slide, disc, or the like, including one or more
microfluidic structures (e.g., channels, wells, chambers,
reservoirs, or any combination thereof), and a
readable-writable-rewritable memory integrated into the substrate,
with the memory being adapted for storing binary coded
information.
[0015] In various embodiments, at least one of the one or more
microfluidic structures comprises a channel having a
cross-sectional dimension of no greater than 500 micrometers (e.g.,
no greater than 250 micrometers, no greater than 100 micrometers,
or no greater than 75 micrometers).
[0016] According to various embodiments, one or more of the
microfluidic structures comprises a chamber, well or reservoir
configured to hold a micro-volume of a fluidic sample, the
micro-volume being no more than about 250 .mu.l (e.g., about 100
.mu.l, 75 .mu.l, 50 .mu.l, or less).
[0017] According to various embodiments, the integrated memory can
be permanently fixed in or to the substrate, or it can be removably
attached to the substrate.
[0018] In various embodiments, the memory is selected from the
group consisting of integrated circuit memories, optical memories,
thin film semi-conductor memories, ferromagnetic memories,
molecular memories, biomolecular memories, and any combination
thereof.
[0019] Various embodiments further include a microcontroller chip
supported by (e.g., integrated into) the substrate and adapted for
communication with the memory.
[0020] In various embodiments, machine-readable computer code is
stored in the memory.
[0021] According to various embodiments, at least one read-only
memory is also integrated into the substrate.
[0022] Further aspects of the invention provide an electrophoresis
microdevice, various embodiments of which comprise a substrate
including one or more microscale structures configured to support
one or more fluidic samples; and a readable-writable-rewritable
memory integrated into the substrate.
[0023] According to various embodiments, an electrophoresis
microdevice can further include (i) one or more electrodes (e.g.,
microelectrodes integrated into the substrate), and (ii) a power
source (e.g., a DC power source); with the one or more electrodes
being connectable to the power source to generate one or more
electrical fields along at least one of the one or more microscale
structures.
[0024] In another of its aspects, the present invention provides a
thermal cycling microdevice, various embodiments of which include a
substrate including one or more microscale structures (e.g., wells
or reservoirs) adapted to receive or support one or more
biomolecule-containing samples (e.g., DNA-containing samples); a
readable-writable-rewritable memory integrated into a region of the
substrate; and a temperature control element or device, adapted to
modulate (cycle) the temperature within at least one of the one or
more microscale structures.
[0025] Another aspect of the present invention provides an
apparatus for acting on one or more biomolecule-containing samples
supported by a microdevice, such as a microdevice including an
integrated readable-writable-rewritable memory. In various
embodiments, an apparatus includes: a housing; a reader-writer unit
mounted in the housing, with the reader-writer unit being adapted
to receive a region of the microdevice into which the memory is
integrated; and a support mounted in the housing, for holding the
microdevice while the samples are acted upon and while the memory
region is received within the reader-writer unit.
[0026] According to various embodiments, an apparatus further
includes a detector operably coupled to a region whereat a
microdevice is located when held by the support.
[0027] In various embodiments, an apparatus further comprises a
temperature control module adapted to regulate the temperature of
at least a portion of a microdevice when held by the support.
[0028] According to various embodiments, an excitation-beam source
(e.g., a laser) is configured to direct an excitation beam of light
along an optical path leading to a region whereat a microdevice is
located when held by the support.
[0029] Further aspects of the present invention provide a system
for acting on samples, and storing and retrieving information
pertaining thereto. According to various embodiments, the system
comprises: a microdevice including one or more microfluidic
structures adapted to support at least one biomolecule-containing
sample; a readable-writable-rewritable memory integrated into the
microdevice; and a reader-writer unit adapted to receive the memory
and to read from, and write/rewrite to, the memory.
[0030] In various embodiments, a system further includes a
sample-processing station; with the reader-writer unit being
mounted in the station.
[0031] According to various embodiments, the memory of a system has
a storage capacity of at least 500 kilobytes (e.g., at least 1
megabyte, at least 10 megabytes, at least 100 megabytes, or
greater).
[0032] In another of its aspects, the present invention provides a
method for acting on one or more fluidic samples, and storing and
retrieving information pertaining thereto. In various embodiments,
a method comprises: (i) providing a microdevice comprising a
substrate including one or more microfluidic structures, and a
readable-writable-rewritable memory integrated into the substrate;
(ii) manipulating one or more fluidic samples in the microfluidic
structures; and (iii) storing binary coded information in the
memory pertaining to the one or more samples.
[0033] In various embodiments, the one or more microfluidic
structures are selected from the group consisting of channels,
chambers, wells, reservoirs, and any combination thereof.
[0034] According to various embodiments, the manipulating step
comprises electrophoresing at least one of the one or more fluidic
samples.
[0035] In various embodiments, the one or more fluidic samples
includes one or more polynucleotides. Additionally, the
manipulating step can comprise amplifying at least one of the one
or more polynucleotides (e.g., by polymerase chain reaction
(per)).
[0036] According to various embodiments, at least 500 kilobytes
(e.g., at least 750 kilobytes, at least 1 megabyte, at least 10
megabytes, or more) of information is stored in the memory.
[0037] Further aspects of the present invention provide a
microdevice, various embodiments of which comprise a substrate
including means for supporting one or more biomolecule-containing
samples; and means for storing binary coded information integrated
into the substrate.
[0038] In various embodiments, the means for storing includes a
storage capacity of at least 500 kilobytes (e.g., at least 750
kilobytes, at least 1 megabyte, at least 10 megabytes, or
more).
[0039] According to various embodiments, the means for storing
comprises a readable-writable-rewritable memory structure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] The structure and manner of operation of the invention may
further be understood by reference to the following description
taken in conjunction with the accompanying drawings, in which
identical reference numerals identify identical or similar
elements, and in which:
[0041] FIG. 1 is a perspective view of a microdevice including an
integrated memory, in accordance with the teachings herein.
[0042] FIG. 2 is a perspective view of a microdevice including a
memory region configured for insertion into a computer-connected
reader-writer unit, in accordance with the teachings herein.
[0043] FIG. 3 is a partially schematic, perspective view, with
portions broken away, of a reader-writer unit incorporated in a
sample-processing station, permitting data to be read, written,
and/or rewritten while a microdevice is operably mounted in the
station, in accordance with the teachings herein.
[0044] FIG. 4 is a partially schematic view of one face of a
disc-type microdevice including a plurality of microfluidic
structures, such as channels, chambers, etc., and a
readable-writable-rewritable memory region, in accordance with the
teachings herein.
[0045] FIG. 5 is a partially schematic, perspective view, with
portions broken away, of a reader-writer unit incorporated in a
sample-processing station, permitting data to be read, written,
and/or rewritten while a spinning-disc microdevice is operably
mounted in the station, in accordance with the teachings
herein.
DESCRIPTION OF THE INVENTION
[0046] Reference will now be made to various embodiments of the
invention, examples of which are illustrated in the accompanying
drawings. While the invention will be described in conjunction with
various embodiments, it will be understood that they are not
intended to limit the invention. On the contrary, the invention is
intended to cover alternatives, modifications, and equivalents,
which may be included within the invention as defined by the
appended claims.
[0047] Aspects of the invention provide a microdevice including one
or more memory structures integrated into the microdevice. Further
aspects of the invention provide a sample processing station
configured for reading from and/or writing/rewriting to the memory
of a microdevice.
[0048] As used herein, the term "integrated" refers to a
configuration wherein memory is fabricated into the body structure
of a microdevice, or is attached to the body structure, such that
the memory and body structure form a single integrated unit. The
attachment can be permanent, or the memory can be removably
attached to the body structure. In an embodiment of the latter, the
memory is securely attached to the body structure until such time
that a user should decide to remove it (e.g., one or more memory
chips can be removably snap-fit to appropriately configured regions
of the body structure).
[0049] A typical microdevice includes a substrate or body structure
that has one or more microscale sample-support, manipulation,
and/or analysis structures, such as a channel, well, chamber,
reservoir, valve or the like disposed within it. As used herein,
"microscale" refers to a fluid channel or conduit that has at least
one cross-sectional dimension, e.g., width, depth or diameter, of
no greater than about 1 micrometer. In various embodiments, such
channels have at least one cross-sectional dimension of no greater
than 750 micrometers, and in certain embodiments, from 1 to 500
micrometers (e.g., between 5 to 250, or between 5 to 100,
micrometers). In one embodiment, a microscale channel has at least
one cross-sectional dimension of between about 10-75 micrometers.
With respect to chambers or wells, "microscale," as used herein,
refers to structures configured to hold a small (micro) volume of
fluid; e.g., no greater than 250-300 .mu.l. In various embodiments,
such chambers are configured to hold no more than 100 no more than
75 no more than 50 .mu.l, no more than 25 .mu.l, no more than 1 or
no more than 50 .mu.l (e.g., about 30 .mu.l).
[0050] A microdevice can be configured in any of a variety of
shapes and sizes. In various embodiments, a microdevice is
generally rectangular, having a width dimension of no greater than
about 15 cm (e.g., about 2, 6, 8 or 10 cm), and a length dimension
of no greater than about 30 cm (e.g., about 3, 5, 10, 15 or 20 cm).
In other embodiments a microdevice is generally square shaped. In
still further embodiments, the substrate is generally circular
(i.e., disc-shaped), having a diameter of no greater than about 35
cm (e.g., about 7.5, 11.5, or 30.5 cm). The disc can have a central
hole formed therein, e.g., to receive a spindle (having a diameter,
e.g., of about 1.5 or 2.2 cm). Other shapes and dimensions are
contemplated herein, as well.
[0051] Chip, wafer, and plate devices (e.g., genetic analysis
microdevices, microchannel electrophoresis devices, per chips,
.mu.TAS devices, lab-on-a-chip systems, sample preparation/cleanup
devices, etc.), spinning disc substrates (e.g., those developed by
Gyros and Gamera), and biomolecule array chips (e.g., those
developed by Hyseq and Affymetrix) have been the subjects of
intensive R&D efforts. Such devices generally permit many
operations to be performed at once on a large number of samples
(e.g., tens, hundreds, thousands, tens of thousands, or more), with
the samples all being the same or substantially the same, all being
different from one another, or some combination thereof. The
present invention combines such structures with a portable or
small-scale memory format; and in various embodiments, a readable,
writable, and/or rewritable memory (or simply, a "rewritable"
memory).
[0052] The present teachings are particularly well suited for
microfluidic devices. The term "microfluidic" refers to a system or
device having channels, chambers, wells, and/or reservoirs (e.g., a
network of chambers and/or wells connected by channels) for
supporting or accommodating very small (micro) volumes of fluids,
and in which the channels, chambers, wells, and/or reservoirs have
microscale dimensions. See, e.g., U.S. Pat. Nos. 6,132,685,
6,103,199, 6,054,277, and 6033546; and EP 1003759; and WO 0126812,
WO 0076662, and WO 9850154; each incorporated herein by
reference.
[0053] A variety of memory structures permitting integration into a
microdevice can be utilized herein, e.g., integrated circuit
memories, optical memories, thin film semi-conductor memories,
ferromagnetic memories (e.g., magnetic stripe memories; see, e.g.,
U.S. Pat. No. 4,281,396; incorporated herein by reference),
molecular memories (see, e.g., U.S. Pat. No. 6,256,767,
incorporated herein by reference), and biomolecular memories (e.g.,
storage devices based upon conformational states of organic
molecules, such as bacteriorhodopsin (BR); see, e.g., Birge et al.,
Biomolecular electronics: Protein-based associative processors and
volumetric memories, J. Phys. Chem. B. 103, 10746-10766 (1999); and
Birge, R., "Protein-Based Three-Dimensional Memory," American
Scientist, July-August 1994, pp. 348-355; each incorporated herein
by reference), etc.
[0054] Thanks in large part to the widespread acceptance and use of
digital cameras, mobile computing devices, personal music players,
etc., small-format memory devices have become well developed in
recent years. Memory cards, such as flash cards, and portable
discs, such as readable-writable-rewritable CDs and DVDs, are
gaining wide use. These, and other, small-format memory devices can
be employed herein.
[0055] According to various embodiments, a microdevice is provided
with, for example, a memory of a type that can store information
even when there is no power supplied to it. For example, a
microdevice can include a flash memory; e.g., the flash technology
utilized in commercial products such as CompactFlash.TM. (by
SanDisk), MemoryStick.TM. (by Sony), SmartMedia.TM. (by Toshiba),
etc. In brief, a typical flash memory, for example, includes flash
memory chips and a microcontroller chip that manages the storage of
digital information (images, data, voice, etc.) and electronic
interfacing. Flash memory is a nonvolatile silicon memory, meaning
that no battery power is required to keep the digital information
stored on the card literally for hundreds of years without
deterioration of information quality. See, for example, U.S. Pat.
Nos. 6,252,791, 5,172,338, 5,663,901, 5,747,359, 5,887,145; and
6,199,122; each of which is incorporated herein by reference.
[0056] It should be appreciated that flash-memory devices are
merely one category of memory that can readily be incorporated into
a microdevice, as taught herein, and that the invention is not
limited to flash memory, but includes a variety of small-format or
portable memory structures capable of being integrated into a
microdevice.
[0057] In various embodiments, the memory is adapted for storing
binary coded information (see, e.g., U.S. Pat. Nos. 4,905,189,
4,477,739, 5,923,583; 4,831,584; each incorporated herein by
reference).
[0058] An integrated memory, as contemplated herein, can be
configured with a variety of storage capacities. In various
embodiments, for example, a microdevice of the invention includes
an integrated memory having a storage capacity of at least 250
kilobytes (kb), at least 500 kb, at least 750 kb, at least 1
megabyte (Mb), at least 10 Mb, at least 100 Mb, at least 250 Mb, at
least 500 Mb, and/or at least 1 Gigabyte (Gb), or higher.
[0059] Microscale sample-support, manipulation, and/or analysis
structures (e.g., channels, chambers, wells, reservoirs, valves,
micro-electronics such as electrodes, etc.) can be formed in or on
a substrate, such as a plate, slide, wafer, chip, disc, or the
like, by fabrication techniques known in the art, e.g.,
photolithographical and/or wet-chemical etching procedures, laser
ablation, electroforming, microcontact printing, microstamping,
micromolding, microcasting, micromachining, engraving, and/or
embossing techniques, to name a few. For example, Backhouse et al.,
DNA sequencing in a monolithic microchannel device, Electrophoresis
2000, 21, 150-156; Dolnik et al., Capillary electrophoresis on
microchip, Electrophoresis 2000, 21, 41-54; Woolley et al.,
Ultra-high-speed DNA fragment separations using microfabricated
capillary array electrophoresis chips, Proc. Natl. Acad. Sci., vol.
91, pp. 11348-11352, November 1994; and Madou, Fundamentals of
Microfabrication, CRC Press, Boca Raton, Fla. (1997) (each of which
is incorporated herein by reference) discuss certain
microfabrication techniques that the skilled artisan can employ in
making microdevices.
[0060] In various embodiments, separation channels are formed in a
generally planar substrate comprised at least in part, for example,
of an electrically insulating material, e.g., fused silica, quartz,
silicate-based glass, such as borosilicate glass, phosphate glass,
alumina-containing glass, and the like, or other silica-like
material(s). According to some embodiments, separation channels are
formed in a plastic substrate.
[0061] One suitable channel microdevice for use in the present
invention is the Standard Microfluidic Chip (Simple Cross,
MC-BF4-SC) from Micralyne Inc. (Edmonton, Alberta, Canada).
Multiple cross-channel or other channel arrangements can be
provided on a single chip or plate, as desired.
[0062] A channel microdevice, as contemplated herein, can include
no more than one channel, or can include a plurality of channels,
e.g., at least 5, 10, 15, 20, 25, or more channels. In an
embodiment, a microdevice for analyte separation includes at least
5, 10 or 15 separation channels.
[0063] In the exemplary arrangement of FIG. 1, a microdevice 10
comprises a substrate (or body) 12 in which sample chambers 14 and
channels 16 are formed (e.g., microfabricated), with a chamber or
reservoir provided in fluid communication with each end of each
channel. More particularly, substrate 12 is comprised of lower and
upper plates, 12a and 12b respectively, with abutted confronting
faces. Lower plate 12a is provided with elongate grooves, each of
roughly semi-circular or semi-oval cross section, that in part
define boundaries for channels 16. The lower face of upper plate
12b is substantially planar, and, when disposed against lower plate
12a as shown, further defines boundaries for channels 16.
Particularly, in the illustrated arrangement, the grooves of plate
12a define lower (floor) and sidewalls or boundaries of each
channel 16 and the lower surface of plate 12b provides an upper
wall or ceiling (boundary) for channels 16. Through-holes can be
formed through upper plate 12b to provide access to, and to define
in part, the chambers 14.
[0064] Lower plate 12a of substrate 12 includes a region, as at 18,
incorporating readable-writable-rewritable memory, such as flash
memory. Memory region 18, in this embodiment, is configured as an
outwardly extending projection, in the plane of lower plate 12a, so
that upper plate 12b does not cover it. The projection can be
configured in a variety of ways. In various embodiments, for
example, the projection is provided with the shape of a standard
PCMCIA card (also known as a PC card).
[0065] According to various embodiments, and with reference to the
exemplary arrangement of FIG. 2, the memory region 18 of a
microdevice 10 can be configured so as to be insertable into a
reader-writer unit 22. The reader-writer unit 22 can be adapted for
communication with a computing device, such as shown at 24, via a
USB or FireWire connection 26. The memory can be written to before,
during and/or after processing.
[0066] Small-format memory reader-writer units are well known (see,
e.g., U.S. Pat. No. 6,149,058; U.S. Pat. No. 6,125,405; U.S. Pat.
No. 6,223,984; JP 10320508; and WO 0067098; each incorporated
herein by reference). Such known units can readily be adapted for
use herein.
[0067] According to various embodiments, and with reference to the
exemplary arrangement of FIG. 3, a reader-writer unit 22 is
incorporated in an apparatus or station 28 configured to carry out
sample processing, such as an automated electrophoresis apparatus,
so that data can be read, written, and/or rewritten while a
microdevice 10 is operably mounted in the processing station 28.
The processing station 28 can include integrated computing
capabilities 32 programmed for receiving and processing data
(alternatively, or in addition, the station 28 can be operably
linked to an external computing device, such as a Macintosh or PC,
and/or to a display-capable input-output device). In the
illustrated embodiment, a human interface device is provided
comprising an externally accessible keypad input/output unit with
an LCD display, shown at 38. A variety of information, such as
results or output generated from use of the station, can then be
written to the integrated memory 18 of the microdevice 10. If
desired, the microdevice can be transported to another computer,
computing-capable processing station, or other desired location,
where the stored information can be accessed, etc. Certain
embodiments contemplate storing the microdevice in a safe place, so
as to archive information held in the integrated memory.
[0068] In some embodiments, a microdevice is configured as a single
or limited-use, disposable unit.
[0069] Various embodiments are particularly adapted to biomolecule
(e.g., DNA, RNA, etc.) sequence or other analysis methods, in which
each of a plurality of different fragment types is labeled with a
spectrally distinctive fluorescent dye. For example, with continued
reference to FIG. 3, processing station 28 can include a support 34
for mounting a microdevice 10 (here, the microdevice being a
multi-channel electrophoresis device having a plurality of
electroseparation channels). A thermal control module 36, e.g.,
Peltier-effect heat-transfer devices, is provided for regulating
the temperature of the microdevice 10. A laser 29 is adapted to
direct an excitation beam of light at a detection zone at a
location along one or more separation channels 16 of the
microchannel electrophoresis device 10. The excitation beam excites
the dyes to emit light. Emitted light from sample zones passes
through a collection lens, through a laser light filter, and
through a focusing lens, indicated collectively at 27. The focused
light is incident on a detector array 31 (e.g., a CCD) capable of
detecting the emissions from the detection zone. Electronic signals
from the detector array can provide information about the character
or sequence of the biomolecule sample. Such information can be
written by a reader-writer unit 22 to an integrated memory 18 of
the device 10.
[0070] In one arrangement, two programs are installed on the
computing portion 32 of the processing station 28, or on the linked
computer, that can collect and analyze data produced by a
micro-channel plate sequencer: (i) a data collection program ("Data
Collection") and (ii) a sequencing analysis program ("Analysis").
Data Collection processes the information as it is generated and
plots the four different emission signals (corresponding to the
four nucleotides) over time during runs. After the runs are
finished, the Data Collection program launches the Analysis
program. Analysis integrates the raw data, normalizes the spacing,
enhances the signal peaks, and uses this information to determine
the parameters for calling the bases. The analyzed data are
re-plotted together as a series of color peaks representing the
nucleotide sequence (i.e., a chromatogram or electropherogram). The
results are stored in a Sample File, which includes the raw data,
the chromatogram, the nucleotide sequence, and the file information
entered by the user. A second file that contains the sequence as
text only is also generated for each sample. This sequence text
file is suitable for use in other applications (e.g., database
searches). See Hagemann et al., ABI Sequencing Analysis, Molecular
Biotechnology, Vol. 13, 137-152 (1999); incorporated herein by
reference. Any one or more of the files can be written to the
memory region 18 of the microdevice 10.
[0071] It should be appreciated that the memory of the microdevice
can store a variety of types of information, including software
applications and/or operation instructions that can be loaded to,
and executed by, a computing device, such as a computing capable
processing station or a desktop computer. In embodiments employing
a rewritable storage medium, the stored information can reflect,
for example, changes in, or processing steps performed on, one or
more samples; sample lineage; plate creation; sample logging;
location management; etc.
[0072] Optionally, a microdevice including an integrated memory can
further include an integrated microprocessor for executing
instructions (code) on-board. In various embodiments, in addition
to readable-writable-rewritable memory, the microdevice further
includes integrated memory storing one or more software
applications and/or operating instructions that can operate on or
otherwise utilize information (e.g., data) written to the
readable-writable-rewritable memory of the device. The additional
memory can also be readable-writable-rewritable memory, or it can
be read-only memory (ROM).
[0073] In a spinning disc microdevice, an example of which is
indicated at 10 in FIG. 4, a region of a disc-like substrate 12 is
configured as a readable, writable, re-writable memory 18 (e.g.,
employing, for example, memory structures as used in CDs or DVDs).
Information can be read, written and/or rewritten as the device is
spinning. This can take place before, during and/or after sample
processing. While exemplary channel 16 and chamber 14 structures
are shown in FIG. 4, it should be appreciated that a variety of
microscale structures can be utilized.
[0074] A variety of spinning disc substrates can be utilized
herein. For example, micro-machined CD-type biomedical devices have
been developed that may be used, for example, to analyze blood
gases and blood electrolytes. Machining options for fluidic
channels with diameters greater than 80 .mu.m include direct CNC
machining in plastic and plastic molding from a metal master
(itself made by CNC machining). With dimensions below 80 .mu.m,
lithography techniques can be used. In some such devices, the
intelligence in the structure resides in the dependence of the
opening of various valves on rotation speed; the faster the disc
spins, the smaller the capillaries that can be accessed by the
fluids. The operating principles of certain centrifugal-based
fluidic platforms are described in more detail, for example, in WO
0040750, WO 0147638, and WO 9853311; each incorporated herein by
reference.
[0075] Reader-writer units and readable-writable-rewritable optical
media, such as CD (e.g., CD-RW) and DVD (e.g., DVD-RW) type media,
are well known (see, e.g., U.S. Pat. No. 5,459,707; U.S. Pat. No.
5,508,988; U.S. Pat. No. 5,465,245; U.S. Pat. No. 6,266,303; U.S.
Pat. No. 5,514,440; EP 0871160; EP 0880780; EP 1091358; each
incorporated herein by reference). Such known units and media can
readily be adapted for use herein.
[0076] FIG. 5 is a partially schematic, perspective view, with
portions broken away, of a reader-writer unit 22 incorporated in a
sample-processing station 28, permitting data to be read, written,
and/or rewritten while a spinning-disc microdevice 10 is operably
mounted in the station. Other components shown in FIG. 5 are
substantially as described with respect to FIG. 3.
[0077] It is contemplated that a variety of types of microdevice
can be configured with a readable-writable memory, in accordance
with the teachings herein. For example, per-capable microdevices
(such as disclosed in WO 0134842; U.S. Pat. No. 6,261,431; U.S.
Pat. No. 6,203,683; each incorporated herein by reference);
electrophoresis microdevices (such as disclosed in U.S. Pat. No.
6,261,430; U.S. Pat. No. 6,045,676; and pending U.S. patent
application Ser. No. 08/726,093 filed Oct. 4, 1996; each
incorporated herein by reference); polynucleotide array
microdevices (e.g., the GeneChip.TM. from Affymetrix, the
HyChip.TM. from Hyseq, and devices such as disclosed in U.S. Pat.
No. 5,445,934; U.S. Pat. No. 5,837,832; EP 1047794; each
incorporated herein by reference); concentration, purification
and/or clean-up microdevices (such as disclosed in U.S. Provisional
Patent Application Ser. No. 60/288,268 filed May 2, 2001; U.S.
Provisional Patent Application Ser. No. 60/318,269 (Attorney Docket
No. 4661P) filed Sep. 7, 2001; U.S. Pat. No. 5,726,026; and WO
9933559; each incorporated herein by reference); spinning-disc-type
microdevices (such as disclosed in WO 0040750, WO 0147638, and WO
9853311; each incorporated herein by reference); JAS devices (such
as disclosed in U.S. Pat. No. 6,194,900; U.S. Pat. No. 5,571,410;
WO 0058724; each incorporated herein by reference);
microelectromechanical system (MEMS) devices (such as disclosed in
U.S. Pat. No. 6,116,863; U.S. Pat. No. 5,909,069; U.S. Pat. No.
5,710,466; and U.S. Pat. No. 5,655,665; each incorporated herein by
reference); to name a few.
[0078] All publications and patent applications referred to herein
are hereby incorporated by reference to the same extent as if each
individual publication or patent application was specifically and
individually indicated to be incorporated by reference.
[0079] Those having ordinary skill in the electrophoresis art will
clearly understand that many modifications are possible in the
above preferred embodiments without departing from the teachings
thereof. All such modifications are intended to be encompassed
within the following claims.
* * * * *