U.S. patent application number 11/198805 was filed with the patent office on 2005-12-08 for medical system, method and apparatus employing mems.
Invention is credited to Cork, William H., Lo, Ying-Cheng, Min, Kyungyoon, Ulmes, James J., Weber, Mark C., West, Richard L..
Application Number | 20050269251 11/198805 |
Document ID | / |
Family ID | 22807884 |
Filed Date | 2005-12-08 |
United States Patent
Application |
20050269251 |
Kind Code |
A1 |
Cork, William H. ; et
al. |
December 8, 2005 |
Medical system, method and apparatus employing MEMS
Abstract
A biological suspension processing system is disclosed that may
include a suspension treatment device for treating one or more
components of a biological suspension, a first fluid flow path for
introducing a suspension into the treatment device and a second
fluid flow path for withdrawing a constituent of the suspension
from the device. At least one microelectromechanical (MEM) sensor
communicates with one of the fluid flow paths for sensing a
selected characteristic of the fluid therewith. The MEM sensor may
be located elsewhere, such as on a container or bag and communicate
with the interior for sensing a characteristic of the fluid
contained therein. A wide variety of characteristics may be sensed,
such as flow rate, pH, cell type, cell antigenicity, DNA, viral or
bacterial presence, cholesterol, hematocrit, cell concentration,
cell count, partial pressure, pathogen presence, or viscosity.
Inventors: |
Cork, William H.; (Lake
Bluff, IL) ; Ulmes, James J.; (Lake Zurich, IL)
; West, Richard L.; (Lake Villa, IL) ; Lo,
Ying-Cheng; (Green Oaks, IL) ; Weber, Mark C.;
(Algonquin, IL) ; Min, Kyungyoon; (Gurnee,
IL) |
Correspondence
Address: |
BAXTER HEALTHCARE CORPORATION
ONE BAXTER PARKWAY
DF2-2E
DEERFIELD
IL
60015
US
|
Family ID: |
22807884 |
Appl. No.: |
11/198805 |
Filed: |
August 5, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11198805 |
Aug 5, 2005 |
|
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|
10031112 |
Jan 14, 2002 |
|
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Current U.S.
Class: |
210/85 ;
210/96.1; 422/62; 436/63 |
Current CPC
Class: |
A61B 50/13 20160201;
Y10T 436/117497 20150115; G01N 33/491 20130101; A61M 2230/20
20130101; G01N 33/5005 20130101; A61B 2562/028 20130101; A61M
2205/12 20130101; G01N 33/5094 20130101; A61M 2205/33 20130101;
A61B 5/14546 20130101; A61M 1/3609 20140204; G01N 2035/00237
20130101; A61B 5/14557 20130101; G01N 35/08 20130101; A61M 1/0209
20130101; A61M 1/3696 20140204; A61M 1/38 20130101; A61M 1/367
20130101; B01D 61/22 20130101; A61M 2205/52 20130101; A61B 5/417
20130101 |
Class at
Publication: |
210/085 ;
210/096.1; 422/062; 436/063 |
International
Class: |
B01D 017/12 |
Claims
1. A biological suspension processing system comprising: a
suspension treatment device for treating one or more components of
a biological suspension; a first fluid flow path, wherein said
first fluid flow path is adapted for continuing, direct
communication with the vascular system of the human subject and the
treatment device for introducing a suspension into the treatment
device; a second fluid flow path communicating with the treatment
device for withdrawing a constituent of the suspension from the
treatment device; at least one microelectromechanical sensor
communicating with one of said fluid flow paths for sensing a
selected characteristic of the fluid within the flow path; and a
controller adapted to receive signals from said sensor and control
the blood treatment device in response thereto.
2. The system of claim 1 in which a sensor senses one or more
characteristics selected from the group consisting of flow rate,
pH, cell type, cell antigenicity, cell concentration, cell count,
viscosity, cholesterol, hematocrit, DNA, viral or bacterial
presence, pathogen presence, and partial pressure of a selected
gas.
3. The system of claim 1 in which a sensor communicates with the
first fluid flow path and generates a signal responsive to one or
more selected characteristics of the fluid in one of the flow
paths.
4. (canceled)
5. The system of claim 1 in which the sensor is adapted to sense
the selected characteristic a plurality of times at discrete
intervals.
6. (canceled)
7. The system of claim 1 in which the sensor communicates with one
of the fluid flow path and senses the approximate quantity or
concentration of a selected cell.
8. The system of claim 1 further comprising a container
communicating with the second fluid flow path for receiving the
withdrawn constituent, the system being adapted to provide tracking
information for associating with the container the particular
characteristic sensed by at least one sensor.
9. The system of claim 8 in which the system comprises machine
readable or human readable data storage media carried by the
container, the data storage media storing information regarding the
particular characteristic sensed by at least one sensor.
10. The system of claim 9 in which the data storage media comprises
a bar code label on the container.
11. The system of claim 9 in which the data storage media comprises
an electronic data storage device.
12. The system of claim 11 in which the electronic data storage
device has a non-volatile semiconductor memory.
13. The system of claim 9 in which the data storage media comprises
at least one icon carried by the container and representative of
the sensed characteristic.
14. The system of claim 9 in which the suspension includes one or
more blood components and the blood component withdrawn is a
cellular component, and the container is for storing the cellular
component withdrawn, and the data storage media includes data
regarding the type, quality, purity, quantity or concentration of
the cellular blood component in the container.
15. The system of claim 1 in which the at least one sensor includes
a first sensor communicating with the first fluid flow path and a
second sensor communicating with the second flow path and the
treatment device comprises an apheresis device and the suspension
comprises whole blood, the first sensor sensing platelets to
determine a platelet count in the suspension introduced into the
apheresis device and the second sensor sensing platelets to
determine a platelet count in the second flow path, wherein the
system includes a container communicating with the second flow path
for storing blood platelets withdrawn, and the system further
comprises machine readable or human readable data storage media
carried by the container, the data storage media storing
information regarding platelet count sensed by one or both of said
sensors.
16. The system of claim 1 in which a sensor communicates with said
second fluid flow path, and said system includes a container for
storing the constituent withdrawn, the sensor generating a signal
responsive to a characteristic of the constituent withdrawn, and
the system includes a data recording device for receiving the
signal and recording data regarding the sensed characteristic of
the constituent withdrawn.
17. The system of claim 16 in which the data recording device
comprises a printer for printing a report of the characteristic
sensed.
18. The system of claim 17 in which the report is in machine
readable graphic format.
19. The system of claim 16 wherein the container carries a machine
readable electronic data storage device, and in which the data
recording device is adapted to transfer data regarding the selected
characteristic sensed by the sensor to the electronic data storage
device.
20. The system of claim 19 in which the electronic storage device
comprises a non-volatile semiconductor memory.
21-45. (canceled)
Description
[0001] The present invention relates generally to medical systems,
methods and apparatus for processing biological suspensions
including, but not limited to, blood. More specifically, the
present invention relates to novel medical systems, methods and
apparatus (for processing biological suspensions) that employ
microelectromechanical systems ("MEMS") as sensors, detectors or
other elements for improving product quality, purity, consistency,
characterization, and/or production.
[0002] The present invention is described below in connection with
the processing of blood and blood components, a field in which it
is expected to find substantial application and benefit. However,
it should be understood that the present invention is not limited
to blood or blood component processing and may be employed in
connection with the processing of other biological suspensions, for
example, bone marrow or cell growth media.
[0003] The processing of blood and blood components has taken on
increased significance in recent years due to the increased demand
for blood and blood components for therapeutic application. Blood
is a suspension of cells or cell fragments that are suspended in a
liquid. The cells include red cells, for carrying oxygen from the
lungs to the muscles and returning carbon dioxide from the muscles
to the lungs, white cells, for fighting infection, and platelets,
for clotting. The cells are suspended in a liquid called plasma,
and the plasma itself has constituents that can be separated
through a process called fractionation. For purposes of this
description, blood "components and blood" constituents are used
interchangeably.
[0004] Red cells are typically needed by patients suffering from
significant blood loss. Platelets are required by many patients
undergoing chemotherapy or radiation treatment, which reduces the
ability of the body to make new bloods cells (and platelets are
among the shortest-lived blood cell). Plasma may be administered to
patients for a variety of reasons, or may be subjected to further
fractionation to isolate and concentrate certain blood
proteins.
[0005] As the demand for blood components has increased, it has
become routine to separate collected blood into its constituent
parts so that only the required constituent is given to the
patient, and the other components or constituents remain available
for other patients, or are returned to the donor. A term commonly
used for separation of blood into one or more constituents is
"apheresis." Apheresis may be done manually, after whole blood is
collected, or it may be carried out in an automated or
semi-automated procedure.
[0006] Automated apheresis typically employs a reusable device or
instrument and a disposable, single use tubing set through which
the blood flows for processing. The collected constituent, such as
platelets, red cells or plasma, is typically withdrawn and directed
to a storage container, or collected within a container inside the
device, and the other blood constituents are either returned to the
donor or separately withdrawn and stored for other uses. A variety
of devices, based on different principles, have been used in
automated apheresis. The most common devices are based on
centrifugation principles, and separate the blood components based
on their different densities. The CS-3000.RTM. and Amicus
separators by Baxter Healthcare Corporation of Deerfield, Ill., and
the Trima.RTM. and Spectra.RTM. separators by Gambro BCT of
Lakewood, Colo., are examples of centrifugal blood separators or
apheresis devices. The Autopheresis-C separator by Baxter
Healthcare Corporation is another type of apheresis device. It
operates on a principle of membrane separation using Taylor
vortices, which is much different than the above-identified
centrifugation devices. The present invention is not limited to a
particular treatment device or principle of operation, and may be
of significant benefit in any of these and other blood or
suspension treatment devices.
[0007] In addition to collection of blood constituents from healthy
donors, the same equipment and processes may be used
therapeutically, to treat ill patients. For example, when it is
believed that a patient may benefit by depleting the amount of
white cells or by removing plasma, the same equipment used with
donors may be used to collect those constituents from patients,
returning the remainder of the blood to the patient. Blood
processing as a therapeutic procedure for a wide variety of
conditions has also grown in recent years.
[0008] Although blood constituent collection or depletion has been
performed for many years, and advances have been made, there remain
significant areas where further improvements are needed. One area
where there is significant need for improvement is in reducing the
potential for human error in the collection and testing of blood
components. In a normal platelet collection procedure, for example,
a number of tests are conducted on the blood withdrawn from the
donor and on the platelet concentrate that is collected. For
example, an incoming blood sample may be withdrawn from the tubing
set and sent to a laboratory for testing regarding platelet count,
the presence of pathogens, blood type, and a variety of other
tests.
[0009] A sample of the collected blood constituent may also be
subjected to similar tests. For platelets, for example, the amount
of collected platelets is a particularly important number, because
a certain amount of platelets (4.times.10.sup.11) is usually
necessary to constitute a standard "dose" or "unit" of platelets.
In addition to determining the number (or, alternatively, the
density) of platelets collected, the collected platelet product
also may be tested for the presence of white cells, which are a
suggested source of adverse reactions in some patients.
[0010] Many of these tests either are not conducted at the same
place the blood component is collected or require 24-48 hours to
complete. Great care must be taken, and numerous administrative
steps completed, to assure that the sample is properly traceable to
the collected blood product, and that the laboratory results are
properly recorded in connection with the particular blood product
collected. Notwithstanding such care, because of the number of
individuals and steps involved, the risk of human error in this
process is real, even if small. Accordingly there is a continuing
need for advances that reduce the amount of human handling and
intervention required, and thus the potential for error as well as
the cost associated with collecting and testing blood constituents.
More specifically, there is a need for collection or treatment
systems that provide a product, such as blood platelets, red cells
or plasma, which is fully or partially characterized, such as by
cell count, pathogen presence, white cell count, blood type, et
cetera, with minimum human intervention and with minimum need for
testing procedures that separate the testing from the treatment
process itself and thereby introduce opportunity for human
error.
[0011] Because the demand for blood components is not constant, it
also is not unusual for certain blood constituents to be wasted due
to outdating before they are used. Although red cells, which may be
refrigerated and stored for lengthier periods of time, blood
platelets are normally stored at room temperature, and have a
limited shelf life of about 5-7 days under the best of
circumstances. Both, however, have limited shelf life, and, as a
result, it is not uncommon for a significant amount of collected
blood constituent product to be wasted because it is not used
within the allowed shelf life period. Thus, in light of the limited
donor pool that is available to contribute platelets and other
blood components, there is a need for better efficiencies in
collecting and using blood components.
[0012] In addition to the above, there is a continuing need for
devices that make the collection process itself more efficient. For
example, the hematocrit and platelet count of a donor may be of
significant value in tailoring or optimizing the collection
procedure to obtain the desired amount of the collected product, in
the desired amount of time, with the desired amount of purity or
freedom from undesirable components, and with minimum adverse
effects to the donor or patient. Although the donor's hematocrit
may be measured reasonably easily prior to a collection procedure,
platelet count is an expensive and time consuming procedure, and
typically is not done prior to the procedure. In most platelet
collection procedures, the best available information is an
estimated platelet count, based on an average of prior donations,
which can vary widely. Accordingly, there is a need for more
current information that can be used to optimize the collection
procedure.
[0013] In summary, there is a continuing need for improvement in
providing blood constituents regarding (1) the consistency of the
collected product, for example in terms of the yield or amount of
constituent collected and available for transfusion or the quality
(e.g., viability) of the blood constituent collected, (2) the
purity of the collected product, for example the absence of
undesirable contaminants and better assurance of completion of all
the necessary testing with reduced chance of human error, (3) the
efficiency of collection and usage of collected blood constituent,
(4) the cost and error potential in the collection and associated
testing and administrative burden and (5) the safety afforded to
the donor.
[0014] Within the past decade significant progress has also been
made in the field of microelectromechanical systems (MEMS). MEMS is
a class of systems that are physically very, very small. These
systems typically, but not exclusively, have both electrical and
mechanical or optical components. Modified integrated circuit
fabrication techniques and materials were originally used to create
these very small devices or systems, but currently many more
fabrication techniques and materials are available.
[0015] MEMS devices have been conceived for a variety of sensing
and actuating functions. MEMS devices have been conceived for
typing blood, counting cells, identifying DNA, performing chemical
assays, measuring pH, sensing partial pressures, and performing a
wide variety of other procedures and tests. Recently, various
manufacturers have even claimed to have developed a "lab on a chip"
that is suitable for carrying out a variety of blood or blood
constituent assays or tests. However, progress in integrating MEMS
devices into pre-existing medical procedures to enhance performance
and reduce potential for human error has been limited.
SUMMARY
[0016] To achieve one or more of the above objectives, the present
invention employs a MEMS sensor in a system for processing a
biological suspension, for example blood, in a treatment device,
wherein the MEMS sensor is employed to sense one or more fluid
characteristics of fluid flowing into or from the treatment device.
More specifically, the present invention may be embodied in a
biological suspension processing system comprising a suspension
treatment device for treating one or more components of a
biological suspension, a first fluid flow path communicating with
the treatment device for introducing a suspension into the
treatment device, and a second fluid flow path communicating with
the treatment device for withdrawing a constituent of the
suspension from the treatment device. In accordance with the
present invention, at least one microelectromechanical (MEMS)
sensor communicates with one of said fluid flow paths for sensing a
selected characteristic of the fluid within the flow path. The
treatment device may be an apheresis device for separating and
collecting one or more blood constituents, but in its broader
aspects, the present invention is not necessarily limited to a
particular suspension treatment device or to a particular apheresis
device or separator.
[0017] Turning back to aspects of the present invention, the MEMS
sensor may be operable to sense a characteristic such as, for
example, one of those selected from the group consisting of flow
rate, pH, cell type, cell antigenicity, cell concentration, cell
count, viscosity, cholesterol, hematocrit, DNA, viral or bacterial
presence, pathogen presence, and/or partial pressure of a selected
gas or other characteristics.
[0018] To aid in control of the system, the sensor may communicate
with the first fluid flow path and generate a signal responsive to
one or more selected characteristics of the fluid (e.g. plate let
count) in the first fluid flow path. The suspension treatment
device may include a controller adapted to receive the sensor
signal and to control the treatment device in response to the
signal. This system could be used, for example, to optimize the
treatment procedure time, to provide a more consistent product, to
provide a product that has a certain minimum quantity of suspension
constituent, or to better safeguard patient affects. A sensor may
also communicate with the second fluid flow path, which conducts
the fluid being withdrawn from the treatment device, for example to
count desired or non-desired components, such as platelets or white
cells, or for other desired purposes.
[0019] For even better control the system may include sensor
adapted to sense a selected characteristic a plurality of times at
discrete intervals. This sensor may generate a signal each time it
senses the characteristic, and the suspension treatment device may
include a controller that is adapted to receive the sensor signal
and to control the treatment device in response thereto. Thus,
periodic sensing may be used to better optimize or improve the
treatment procedure over all or part of the treatment procedure.
For example, the sensor may communicate with the second fluid flow
path and sense the approximate quantity or concentration of a
selected cell, with the controller controlling the system to
collect a desired quantity of the selected cell, or alternatively,
to reduce the collected amount of the selected cell.
[0020] The system may further comprise a container communicating
with the second fluid flow path for receiving the withdrawn
constituent, with the system being adapted to provide tracking
information for associating with the container the particular
characteristic sensed by at least one sensor. A machine readable or
human readable data storage media may be carried by the container
to store information regarding the particular characteristics
sensed by at least one sensor. The data storage media is not
limited to a particular type, and may comprises a graphic indicator
such as a bar code label on the container, an electronic data
storage device, such as one with a non-volatile semiconductor
memory, or an icon or other graphic carried by the container
representative of the sensed characteristic. This tracking may be
entirely carried out by the system, thereby reducing the
possibility of human error in mishandling of the sample or
information.
[0021] When the suspension includes one or more blood components
and the blood component withdrawn is a cellular component, the
system may include a container for storing the cellular component
withdrawn, and the data storage media may include data regarding,
for example, the type, quality, purity, quantity and/or
concentration of the cellular component in the container. More
specifically, the system may include a first sensor communicating
with the first fluid flow path and a second sensor communicating
with the second flow path and the treatment device may comprise an
apheresis device. When the suspension comprises whole blood, the
first sensor may sense inter alia, platelets to determine a
platelet count in the suspension introduced into the apheresis
device and the second sensor may sense inter alia, platelets
withdrawn to determine a platelet count in the second flow path. A
container communicating with the second flow path may be provided
to store the blood platelets withdrawn, and the system may further
comprises machine readable or human readable data storage media
carried by the container for storing information regarding platelet
count sensed by one or both of said sensors. To reduce the number
of human interventions required, the system may itself include a
data recording device for receiving a signal from one or more of
the sensors and recording the data regarding the sensed
characteristic. The data recording device may be a printer for
printing a human or machine readable report of the characteristic
sensed, such as directly on the container or on a label affixed to
the container. Alternatively, the container may carry a machine
readable electronic data storage device, and the data recording
device be adapted to transfer data regarding the selected
characteristic sensed by the sensor to the electronic data storage
device. An electronic data storage device may preferably comprise a
non-volatile semiconductor memory, or "write once, reads many
times" memory so that the data is not inadvertently lost or
destroyed by power loss. In other words, a memory or processing
chip may be added to the blood constituent storage container, such
as permanently mounted in the tail flap of the container, with a
non-volatile memory, for receiving and storing data for later
access by the appropriate electronic reading instrument.
[0022] The blood component storage container also may include a
microelectromechanical sensor carried by the container and
communicating with the container compartment for sensing a selected
characteristic, for example just before administration to a
patient, of the blood component received or stored therein. Such a
sensor similarly may include a non-volatile semiconductor memory or
so-called "write once, read many times" data storage.
[0023] In accordance with another aspect, the present invention may
be directed to a blood processing system for providing a
characterized blood constituent product in which the system
comprises: an apheresis device for separating one or more desired
cellular blood constituents from a suspension comprising whole
blood, a first fluid flow path communicating with the apheresis
device for introducing a suspension comprising whole blood into the
device, a second fluid flow path communicating with the apheresis
device for withdrawing at least one desired cellular blood
constituent from the device, a container communicating with the
second fluid flow path for receiving the blood constituent
withdrawn from the apheresis device, machine readable or human
readable data storage media carried by the container, at least one
microelectromechanical sensor communicating with the first fluid
flow path for sensing at least one characteristic of the whole
blood and for generating at least one electrical signal responsive
to such sensing, at least one microelectromechanical sensor
communicating with the second flow path for sensing the quantity of
cellular blood constituent withdrawn from the apheresis device and
for generating an electrical signal responsive to such sensing, a
data recorder adapted to receive the electrical signals from the
sensors and to record data regarding the sensed characteristics on
the data storage media, whereby a user may readily identify the
sensed characteristic regarding the whole blood and the quantity of
the desired cellular constituent in the container with a minimum of
human intervention.
[0024] This system may further include a sensor communicating with
the second fluid flow path for sensing the quantity of a
non-desired biologic constituent in the flow path and generating an
electrical signal responsive to the quantity, the data recorder
being adapted to receive such signal and record data regarding the
quantity of non-desired cellular constituent in the data storage
media for access by a user of the product in the container. The
non-desired biologic component may be a viral constituent, or a
cellular constituent, such as white cells.
[0025] As before, the system may include a controller adapted to
receive the signals from the sensors communicating with the first
and second fluid flow paths and to control the apheresis device in
response to one or more of such signals to provide a desired
cellular blood constituent product characterized by data recorded
in the data storage media in accordance with characteristics sensed
by the sensors. The data storage media may comprise machine
readable graphics carried on the container, for example, a bar
code. The system may also, when withdrawing blood from a donor or
patient, for example, generate a human-readable report for the
donor or patient containing selected data regarding one or more of
the sensed characteristics.
[0026] In accordance with another aspect of the present invention,
a biological suspension processing system may be provided which
includes: a blood treatment device for treating one or more
components of a biological suspension, a human subject, a first
fluid flow path communicating with the vascular system of the human
subject and the treatment device for introducing blood from the
human subject into the treatment device, a second fluid flow path
communicating with the treatment device for withdrawing a
constituent of the blood from the treatment device, a third fluid
flow path communicating with the treatment device from withdrawing
another constituent of the blood from the treatment device, and at
least one microelectromechanical sensor communicating with one of
said fluid flow paths for sensing a selected characteristic of the
fluid within the flow path.
[0027] The sensor may generate a signal responsive to one or more
selected characteristic of the fluid in one of the fluid flow path,
with the suspension treatment device including a controller adapted
to receive the sensor signal and to control the treatment device in
response thereto. In the situation where the third fluid flow path
communicates with the human subject, and the treatment device is
adapted to add anticoagulant to the blood in the first fluid flow
path, the selected characteristic may include the hematocrit of
blood in the first fluid flow path. In that setting, the controller
may control the addition of anticoagulant into the first fluid flow
path to prevent too much anticoagulant from being returned to the
donor or patient, because, as is well known excess anticoagulant
flow to the donor or patient may have deleterious consequences.
[0028] The signal from the sensor and the control of the treatment
device is not limited, however, to the safety of the human subject.
The controller may, for example, in response to the signal control
the treatment device to withdraw a constituent of desired quality,
to withdraw a constituent of desired quantity, to withdraw a
constituent that is depleted of an undesired component, or to
withdraw a selected minimum quantity of constituents, such as
platelets, red cells or plasma, or to withdraw a certain amount of
constituent in a maximum or minimum procedure time.
[0029] In a more specific embodiment of the present invention, the
MEMS sensor(s) or other MEMS devices are located on a common
disposable carrier or cassette. The carrier includes internally
defined fluid flow passageways that may be selectively opened or
closed by macro or MEMS scale valves to control flow of fluid to
the sensors in response to control signals from the device
controller. The carrier is preferably adapted to interfit with a
reusable reader/controller which cooperates with the MEMS devices
located in the cassette to provide a signal responsive to the
sensed characteristic, which signal may be used to optimize the
treatment procedure or to identify the sensed characteristic for
later association with or labeling of the collected blood product,
or to control the flow of fluid through the cassette.
[0030] Although the carrier may take several different forms, in
one form of a cassette, it is comprised of a rigid plastic base
that mounts a plurality of MEMS sensors or other MEMS devices such
as valves or pumps, and has preformed passageways defined in the
base with fluid flow control valve modules located to control the
flow of selected fluid to the desired MEMS sensor. The cassette may
include preformed open passageways that are closed by a resilient
membrane which overlies one side of the cassette and is sealed to
the passageway walls (either temporarily by pressure exerted by the
reader or permanently by solvent or sonic bonding) to close the
passageways. The membrane may cooperate, such as by mechanical or
pneumatic actuation, with the valve modules to control the flow of
fluid through passageways in the MEMS cassette.
[0031] The present invention is not limited to a particular type of
MEMS sensor or to a particular principle of operation. The MEMS
devices useful in the present invention may be static or dynamic,
purely mechanical, biomechanical or electromechanical. They may
also include optical components, and they may be dry or used in
combination with liquid reagents or other liquids.
[0032] One type of MEMS sensor that holds promise for apheresis
procedures is a microcytometer in which particles, for example
cells, or cell fragments, are fed through a narrow, microfluidic
channel in single file. Other MEMS sensors may be based, for
example, on centrifugal microfluidics analysis employing a rotating
compact disc that employs, for example, a micro-fluidics manifold
and spectrophotometric cuvette formed on the surface of the disc,
which may be read by an optical disc reader.
[0033] Because certain MEMS devices may require special or separate
sterilization procedures as compared to other MEMS devices, the
present invention also contemplates that there may be more than one
MEMS carrier or cassette. For example, MEMS employing reagents may
require a different sterilization technique, such as ethylene oxide
sterilization, as compared to purely mechanical or
electro/mechanical, optical/mechanical or optical/electrical MEMS
devices, which may be suitable for radiation or heat sterilization.
There may also be other reasons for having more than one MEMS
cassette, including ease of manufacturing, ease of mounting or
assembly on the treatment device, and the like. In such case, the
MEMS cassette may be attached to the remainder of the fluid circuit
after sterilization, as by sterile docking or other sterile
connection procedure.
[0034] Fluid may be pumped through the MEMS cassette by the
peristaltic pumps that are typically employed on apheresis devices
for moving blood and blood components through the tubing set or,
alternatively, the MEMS cassette itself may include macro and/or
MEMS-scale pumps for circulating fluid through the MEMS cassette
and to the desired MEMS sensor. Similarly, liquid flow through the
cassette may be controlled by MEMS scale valves, or by macro scale
valves such as those employed in the fluid flow control modules of
the Amicus apheresis centrifuge marketed by Baxter Healthcare.
[0035] Additional aspects and features of the present invention are
set forth in the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] FIG. 1 is schematic flow chart of a suspension treatment
system embodying the present invention.
[0037] FIG. 2 is a software/data flow chart for a control and data
flow system that may be employed in the present invention.
[0038] FIG. 3 is a perspective view of a reusable suspension
treatment device, specifically an apheresis device, embodying the
present invention.
[0039] FIG. 4 is an enlarged perspective view of a portion of the
device of FIG. 3, showing the reader/controller for a MEMS cassette
or carrier.
[0040] FIG. 5 is a plan schematic of a disposable fluid circuit,
including a MEMS cassette or carrier, for use with the device of
FIG. 3 and employing the present invention.
[0041] FIG. 6 is an exploded perspective view of a MEMS cassette or
carrier that may be used in the disposable fluid circuit of FIG. 5,
embodying the present invention.
[0042] FIG. 7a is a top view of the assembled MEMS cassette of FIG.
6.
[0043] FIG. 7b is a side view of the MEMS cassette of FIG. 7a.
[0044] FIG. 8 is a perspective view of the reader/controller for
the MEMS cassette.
[0045] FIG. 9 is an enlarged perspective view of the device of FIG.
3, embodying an alternative MEMS cassette reader/controller.
[0046] FIG. 10 is an exploded perspective view of a MEMS cassette
that may be used with the reader/controller shown in FIG. 9.
[0047] FIG. 11 is a rear perspective view of the assembled MEMS
cassette of FIG. 10, illustrating macro-scale valve modules for
fluid flow control.
[0048] FIG. 12 is an enlarged perspective view showing the interfit
between the MEMS cassette of FIG. 10 and the reader/controller of
FIG. 9.
[0049] FIG. 13 is a schematic view of MEMS microcytometer that may
be used in the present invention.
[0050] FIG. 14 is a view of the microcytometer of FIG. 13,
illustrating the focusing of blood cells using sheath flow.
[0051] FIGS. 15a and 15b are cross-section views of a bistable
valve that may be used in the MEMS cassette of the present
invention.
[0052] FIG. 16 is a top plan view of an alternative MEMS cassette
embodying the present invention, which includes fluid pumping
chambers for pumping fluid through the cassette.
[0053] FIG. 17a is a plan view of a compact disc employing a
microfluidic manifold and a spectrophotometric cuvette.
[0054] FIG. 17b is an elevational view of a reader for the compact
disc of FIG. 17a.
[0055] FIG. 18a is a plan view of a blood component storage
container having a MEMS sensor mounted in or carried on the
container wall for accessing the contents.
[0056] FIG. 18b is a plan view of the container of FIG. 18a with a
reader for reading the MEMS sensor.
DETAILED DESCRIPTION OF DRAWINGS
[0057] Turning now to a more detailed description of the drawings,
FIG. 1 is a flow chart illustrating a treatment system embodying
the present invention. Although the flow chart in FIG. 1 is in the
context of a blood apheresis system, the flow chart and the steps
indicated therein have application to other suspension treatment
systems as well.
[0058] Before describing the treatment system in more detail, it
should be understood that the flow chart is intended to reflect
general system features and functions, and not necessarily the
system structure. For example, it should be understood that
features shown in a single box or grouping of the flow chart may
represent what are actually two or more physical modules or
structures in the actual product, and more than one box or grouping
in the flow chart may be a single physical module or structure in
the final product. The purpose of the flow chart is simply to
illustrate one embodiment of an overall system and function, and
not to limit the actual physical structure.
[0059] As applied to apheresis, the system in FIG. 1 includes an
apheresis device 50, such as a centrifuge, spinning membrane
separator or other apheresis device or instrument, and an
instrument or device control system 52. The control system 52,
which may comprise a programmable microprocessor, performs a
variety of control and monitoring functions for carrying out an
apheresis procedure. It receives and sends data regarding various
initial, in-process and final product characteristics, it controls
the fluid flow through the system, it controls the operation of the
apheresis device and it tracks and stores data for labeling the
final product or for communicating with data storage media
associated with the container in which product is collected during
the apheresis procedure.
[0060] In the system shown in FIG. 1, whole blood is collected from
a donor 54, such as a healthy adult human. The flow of blood (and
other liquids such as priming solution and anticoagulant) through
the system is controlled by a fluid management module 56. In
accordance with the present invention, one or more characteristics
of the blood flowing into the system may be sensed by one or more
MEMS sensors. For example, an initial sample of the whole blood,
before processing, may brought into contact with one or more
initial condition MEMS sensors 58 for sensing or measuring red cell
count, platelet count, lipid level, blood type or markers
representative of pathogen (viral or bacteria) presence. As used
here, "sensor" or "sensing" is used broadly and includes detecting,
measuring, monitoring, analyzing, characterizing, sampling and any
other tests or analysis that may be desired.
[0061] Data from the initial conditional sampling, typically in the
form of an electrical signal, may be fed back to the control system
52 for purposes, for example, of controlling the fluid management
module or the apheresis separation process or for tracking or
storing information relating to the sensed characteristic for later
association with the collected product. For example, data as to
blood type may be saved for recording on a machine readable or
human readable data storage media carried by the container for the
collected product, such as a descriptive label, bar code or
electronic memory device. Data regarding initial platelet count may
be used, for example, to optimize the apheresis procedure to
minimize procedure time, to maximize the amount of platelets
collected or to better assure collection of a certain minimum
number of platelets.
[0062] The anticoagulated whole blood is directed by the fluid
management module to the apheresis device or instrument 50. There,
the blood is separated into one or more components, such as
components nos. 1, 2 and up to "n" components. During the apheresis
procedure, in-process data may be sensed by one or more of the
in-process condition MEMS sensors 60, for detecting characteristics
such as white cell count, red cell hematocrit and platelet density.
Data from the in-process condition MEMS sensor(s) may be fed back
to the control system 52, typically for controlling the apheresis
process and/or fluid flow. The in-process condition MEMS sensor may
sample fluid one or more times during the procedure, as desired. To
provide periodic adjustment of the apheresis device or fluid flow
throughout the apheresis procedure, a plurality of MEMS sensors may
be employed in the in-process sensing. These MEMS sensors may be
activated by the control system to sense one or more selected
characteristic at selected time intervals throughout the procedure
or upon occurrence of certain triggering events, such as power
outage, red cell spill over or other event.
[0063] The separated blood components not returned to the donor are
directed to storage containers 64, 66 and 68, respectively. It is
not necessary, of course, for the storage containers to be outside
of the apheresis device. In the Baxter CS-3000.RTM. and Amicus.RTM.
centrifuges, for example, blood components may be collected in
containers that reside inside the rotating centrifuge until the
apheresis procedure is completed.
[0064] As one or more components are collected, one or more
characteristics of the final collected product may be sensed by the
MEMS final product condition sensor(s) 62 and data relayed back to
the controller 52. The final product condition MEMS sensor 62 may
be provided to sense one or more characteristics of the collected
product, such as white cell count, packed red cell hematocrit,
platelet dose, pH, or gas (e.g., CO.sub.2 partial pressure. The
final product condition MEMS may feed data back to the control
system 52 for optimizing the apheresis procedure, controlling fluid
flow and/or storing/tracking data for association with the final
collected product.
[0065] One of the benefits of certain aspects of the present
invention is the providing of a final product that is fully or
partially characterized according to the initial condition,
in-process and/or final product condition MEMS sensors, with the
characteristics sensed being tracked or stored for association with
the final product container, all occurring with reduced human
intervention and opportunity for error. For example, having
received data from the various MEMS condition sensors 58, 60 and
62, the instrument control system 52 may relay that data to a
recorder or labeler 70, which records the data onto data storage
media 72 carried by the storage container. The data or storage
media may be human readable, or machine readable (e.g., graphic or
bar code), or a combination of both or other form. The recorder
may, for example, print a label for attachment to the container, or
transfer the data to a machine readable electronic storage device,
such as a memory chip, carried by the container. The result is a
blood component product characterized as needed, with reduced need
for human intervention or opportunity for human error.
[0066] FIG. 2 is an outline of certain aspects of a programmable
operation control system. As shown there, the procedure process
master control module 74 may instruct (shown by dashed lines)
various elements of the system to perform certain functions, and
receive (shown by solid lines) data from one or more of those
elements. For example, the master control may direct the sample
pre-measurement module 76 to carry out certain initial condition
sensing. This may be carried out by opening a macro or MEMS-scale
valve that directs incoming whole blood into contact with the
desired initial condition MEMS sensor 58. The information or data
regarding the sensed characteristic is then relayed back through
the pre-measurement module to the master control module for storage
or for later association with the collected blood product.
[0067] Similar steps may be carried out as between the master
control module 74 and the in-process module 78 and in-process MEMS
sensor(s) 60, and as between the master control module and the
final product configuration module 80 and final product condition
sensor(s) 62.
[0068] Information from the various MEMS sensors may then be
relayed to the recorder/labeler 70 for associating the data with
the final product container. In one simple form, this may be by way
of printing a label for attachment to the container or for printing
the desired information on a pre-attached label, although the
present invention also contemplates that data could be transferred
optically or electrically to an electronic data storage device
(such as a non-volatile memory chip or "write once, read many
times" storage device) attached to the final product container. If
the operator desires that only certain information be displayed
with the product, the system permits less than all of the
characteristics that are sensed to be displayed on or in connection
with the collected product.
[0069] FIG. 3 shows a biological suspension treatment device, and
specifically an Amicus.RTM. apheresis instrument 82 of the general
type made and sold by Baxter Healthcare Corporation of Deerfield,
Ill. The Amicus.RTM. separator is described in detail in U.S. Pat.
No. 5,462,416, which is incorporated by reference, and that
description will not be repeated in full here.
[0070] Briefly, the Amicus.RTM. separator is based on
centrifugation principles, and separates blood components by reason
of their different densities. The Amicus.RTM. separator is intended
to work with a disposable, one-time use plastic tubing set, which
will be described later, through which blood and blood components
flow during the apheresis procedure.
[0071] The Amicus.RTM. separator includes a base portion, generally
at 84, a fluid management and sensor panel area 86, and a display
screen and touch control panel 88. The machine base 84 contains the
rotating centrifuge chamber drive hardware and control electronics.
The centrifuge chamber is accessible through a drop-down front door
90 for loading and removing the disposable tubing set.
[0072] The fluid management and sensor panel includes three pump
and valve stations, each of which has a pair of peristaltic pumps
92 and adjacent flow control module 94 for pumping fluid through
the system and controlling the direction of fluid flow. User
information regarding the apheresis procedure is displayed on the
display screen 88, which also includes touch input capability for
operator entry of information or control commands prior to and
during the apheresis procedure.
[0073] In accordance with a preferred version of the present
invention, the MEMS sensors and other devices are mounted on a
single MEMS carrier or cassette 96 (FIG. 5), which is part of the
disposable fluid circuit and intended for one-time use only. The
apheresis instrument 82 (FIG. 3) includes a MEMS cassette
reader/controller 98 into which the MEMS cassette is mounted when
the disposable fluid circuit is installed on the instrument. The
reader/actuator 98 cooperates with the MEMS cassette for reading or
transferring data from the MEMS sensors on the cassette and for
controlling flow of fluid through the MEMS cassette and to the
desired MEMS sensor or other MEMS device.
[0074] The MEMS cassette reader/controller shown in FIG. 3, and
shown in larger view in FIG. 4, employs a base 100 adapted to
receive the MEMS cassette and a door 102 pivotally mounted on the
base for closing over the cassette to block out ambient light and
cooperate with optical, electronic or mechanical devices located in
the base portion for reading or interpreting the MEMS sensors or
other devices and/or for actuating valves or pumps located in the
MEMS cassette.
[0075] FIG. 5 is a schematic view of a disposable one-time-use
processing assembly or fluid circuit 104 embodying the MEMS
cassette/carrier 96 of the present invention for use on the
apheresis instrument shown in FIG. 3. A detailed description of the
disposable fluid circuit may be found in U.S. Pat. No. 5,462,416,
which was previously incorporated by reference, and will not be
repeated here.
[0076] The processing assembly 104 includes an array of flexible
tubing that forms the fluid circuit through which blood and blood
components flow. The fluid circuit conveys liquid to and from a
processing chamber 106 that is mounted in the rotating centrifuge
chamber during use. The fluid circuit includes a number of
containers 110a-f that fit on hangers on the centrifuge assembly to
dispense and receive liquids during the apheresis process.
[0077] The fluid circuit 104 also includes one or more in-line
fluid control cassettes 112, which are not to be confused with the
MEMS cassette (although the fluid control cassettes could also
include MEMS sensors or other MEMS devices and thus incorporate
features of the present invention, if desired). FIG. 5 shows three
such cassettes designated 112a, 112b and 112c. The cassettes serve
in association with the pump and valve stations on the centrifuge
assembly to direct liquid flow among the multiple liquid sources
and destinations. During a blood processing procedure the cassettes
centralize the valving and pumping functions to carry out the
selected procedure. Further details of these functions are
described in the above mentioned U.S. Pat. No. 4,562,416.
[0078] A portion of the fluid circuit 108 leading between the
cassettes 112a-c and the processing chamber 106 is bundled together
to form an umbilicus 114. The umbilicus links the rotating parts of
the processing assembly (principally the fluid management
processing chamber) with the non-rotating, stationary parts of the
processing assembly (principally the cassettes and containers and
fluid circuit tubing and MEMS carrier or cassette). The umbilicus
links the rotating and stationary parts of the processing assembly
without using rotating seals, by employing the well known one-omega
two-omega principle, which has long been successfully used in the
CS-3000.RTM. centrifuge marketed by Baxter Healthcare
Corporation.
[0079] In the illustrated and preferred embodiment, the fluid
circuit 104 pre-connects the processing chamber 106, the containers
110, the fluid control cassettes 112 and the MEMS carrier/cassette
96. The assembly thereby preferably forms an integral pre-assembled
sterile unit, although it is recognized that if separate
sterilization is required for the MEMS cassette, it may require
subsequent attachment, such as by sterile connection procedure, to
the remainder of the fluid circuit.
[0080] During a typical dual needle platelet collection procedure,
whole blood is drawn into an inlet needle 116 and combined at a
junction 118 with anticoagulant such as ACD, which is pumped from
the ACD container 110d, through fluid control cassette 112a and
from there into the separation/processing chamber 106. In the
separation chamber, platelet rich plasma is separated from packed
red cells, and each is withdrawn from the separation chamber. The
platelet rich plasma is withdrawn through the umbilicus 114
upwardly through cassette 112c and then, after passing through an
optical sensor 120, returned to a collection chamber in the
centrifuge. There, platelet concentrate is separated from the
platelet rich plasma, and platelet-depleted or platelet-poor plasma
is withdrawn from the collection chamber and collected in a
platelet-poor plasma storage container 110c and/or returned to the
donor, with red cells through fluid control cassette 112a and
return needle 117. Although illustrated as a dual needle set, the
present invention is equally applicable for a single needle fluid
circuit of the type also previously sold by Baxter Healthcare
Corporation for use on the Amicus.RTM. centrifuge.
[0081] In accordance with the present invention, as illustrated in
FIG. 5, the fluid circuit 104 includes at least one MEMS cassette
or carrier 96. As shown in FIG. 5 for purposes of illustration and
not limitation, the MEMS cassette 96 is shown having five fluid
connections. The number of connections, however, depends on the
fluid characteristics to be sensed, and fewer fluid connections may
suffice for many blood-related applications, as will be discussed
later.
[0082] As illustrated in FIG. 5, the MEMS cassette 98 has a fluid
inlet 120 connected to the packed red cell line. Fluid in this line
may be monitored by MEMS sensors to determine the packed red cell
hematocrit for the purpose, for example, of optimizing the
separation procedure.
[0083] MEMS cassette fluid inlet 122 is connected to the whole
blood inlet line. Fluid from this line may be sensed by MEMS
sensors, for example, to determine any of the initial condition
data such as red cell count, platelet count, lipid level, blood
type or the presence of a pathogen (viral or bacteria) indicator or
marker.
[0084] The next fluid entry inlet line 124, is shown communicating
to the platelet rich plasma line. This may be used to perform
in-process analysis of white cell count, red cell hematocrit,
platelet density and the like.
[0085] Fluid connection 126 is connected to the platelet-depleted
plasma line. MEMS sensors associated with this connection may be
used to sense any of the desired final product characteristics of
the plasma. Similarly, fluid connection 128 is attached to the
platelet concentrate collection tubing for MEMS sensing of one or
more of the final characteristics of the platelet concentrate, such
as platelet dose or density, white cell count, platelet size, and
the like.
[0086] A MEMS cassette or carrier 98 as presently contemplated is
depicted in greater detail in FIG. 6. As shown there, the cassette
includes a rigid MEMS holder or support 130, a plurality of MEMS
sensors or other MEMS devices 132, front cover 134 and membrane
backing 136. The holder or support 130 is preferably made of rigid
plastic or other suitable material. A plurality of passageways 138
for fluid flow are provided in the MEMS holder, for communicating
the desired fluid to the desired MEMS sensor or other device. As
illustrated in FIG. 6, three such fluid passageways 138 are shown
for initial condition, in-process, and finished product
characteristic sensing. The passageways are pre-formed into the
MEMS holder, and communicate with three arrays of MEMS
device-receiving areas 140, which are adapted to receive the
desired MEMS sensors or other devices. The center fluid passageway
communicates with two rows of MEMS device receiving areas that
flank the passageway. The other two passageways communicate with a
single row of MEMS devices. The size of the array and number of
MEMS sensors or other devices may be varied as needed for a given
treatment procedure to provide the desired sensing capability. For
those MEMS sensors or other devices that require an electrical
power source, the rigid holder may include a plurality of
electrical contacts 142. Embedded or embossed electrical leads in
the holder may extend between the contacts and the appropriate
areas 140 for mounting MEMS sensors or other devices that require a
voltage source.
[0087] The MEMS holder and MEMS sensors/devices are contained
beneath the clear cover plate 134, which is sealed to the holder
130, as by adhesive, sonic or solvent bonding, to form the
passageways 138. The clear cover allows for the transmission of
light to or from associated optical light sources or receivers in
the MEMS cassette reader. The flexible membrane 196 attached to the
underside of the MEMS holder allows for actuation of valves, pumps
or other devices associated with the MEMS cassette, as described in
more detail later.
[0088] Turning to FIG. 7A, which is a plan view of the MEMS
cassette or carrier 98, the initial condition analysis sample line
144 communicates with a first fluid passageway 138a in the MEMS
cassette that communicates with a plurality of MEMS sensors for
sensing viral or pathogen markers (e.g., a DNA analysis that may
reveal the presence of an unwanted virus or bacteria), blood type,
lipid level, platelet count and red cell count. The inlet to each
MEMS sensors may be controlled by a valve 141, which may be
macro-scale valve that controls flow of the initial fluid to the
MEMS sensor or by MEMS-scale valves, which are available from a
variety of sources using various principles, such as surface
tension, flexing membranes or the like. It is contemplated that the
initial condition line would communicate, in an apheresis
procedure, with the whole blood inlet line. Additionally, although
the passageways 138 are shown as having closed ends, the
passageways may also continue through the cassette and return to
the fluid circuit so that, for example, the sample lines are
receiving a constant throughput of the fluid to be analyzed.
[0089] The next inlet line is the in-process analysis sample line
146, which communicates with the fluid flow passageway 138b in the
MEMS cassette for sampling various characteristics of the fluid
while the apheresis process is carried out. For example, the
in-process fluid may flow through the center passageway 138b to
platelet density MEMS sensors, red cell MEMS sensors and MEMS
sensors for counting the number of white cells. The in-process flow
line may be attached to the platelet-rich plasma line, the packed
red cell line or, if desired, with the processing chamber
itself.
[0090] The final product analysis sample line 148 communicates with
the third passageway 138c in the MEMS cassette for determining
final product characteristics, such as partial pressure of
CO.sub.2, the pH, the platelet density, hematocrit or white cell
count. It is anticipated that this final product sample line would
be connected to the flow line communicating with the final product
collection container, although other connection sites, such as the
processing chamber itself, are within the scope of this
invention.
[0091] Although the characteristics described above are these that
may be determined in the platelet collection procedure, the user
may select or the manufacturer may employ different MEMS sensors
with different objectives or for sensing different characteristics,
as desired.
[0092] As shown in FIG. 8, in use, the MEMS cassette or carrier 96
is preferably mounted within a recessed area in the base 100 of the
MEMS cassette reader/controller 98. For MEMS devices employing
optical read-out, the base preferably includes an array of light
emitting fibers or diodes 150 in registration with the appropriate
MEMS devices, and the door 102 may include an array of light
collectors or receivers 152 in registration with the MEMS devices
for the purpose of reading the optical transmission, reflection or
refraction by the particular MEMS sensor. The base and/or door also
include electrical contacts 153 for connecting with electrical
contacts 142 of the cassette for MEMS needing an electrical voltage
source. Therefore, it is apparent that the present invention is not
limited to a particular type of MEMS sensor or device or to MEMS
sensors or devices operating on a particular principle.
[0093] One example of a MEMS sensor for use in the present
invention is illustrated in FIG. 13. The MEMS sensor shown there is
a MEMS microcytometer 149, and is believed to have particular
promise for cell-related applications. As may be seen there, the
microcytometer includes a light source 150 for emitting light, such
as coherent laser light, at a single file stream of components,
such as cells which may be received from the initial condition, in
process or final condition flow lines. Light receivers 152 and 154,
receive reflected and refracted light from the particles which, in
turn, is used to count or characterize the cells flowing through
the line, such as by cell type, cell density or number of cells.
Fluorescence detection and light scattering can be used to count
and characterize the cells. Such detection may also be combined
with immunossays techniques to detect and characterize antibody
coated beads and antibody-antigen complexes. This type of MEMS
sensor has been previously described by, and may be available from
Micronics, Inc., of Redmond, Wash.
[0094] As shown in FIG. 14, the microcytometer 149 employs a
micro-fluidic channel 151 in which fluid flowing in a sheath flow
arrangement resulting from liquid flow from the intersecting flow
channels 153 forms the cells into single file for analysis.
Accordingly, it is within the concept of the present invention that
the MEMS cassette may also include additional fluid channels 153,
as appropriate, for receiving liquids or gases (such as saline,
water, reagents, or other liquids or gases) that may be used in
connection with the MEMS sensors.
[0095] Another MEMS device that may be suitable for application in
the present invention is a MEMS sensor based on centrifugal
microfluidics analysis. One or more small rotating compact discs
may be mounted in the MEMS cassette, which disc may be read by an
optical disc reader. The disc employs, for example, a
micro-fluidics manifold and spectrophotometric cuvette formed on
the surface of the disc. FIG. 17 diagrammatically depicts such a
device, which has been proposed by and may be available from Gamera
Bioscience of Medford, Mass.
[0096] Microfluidic mixing devices, capillary connectors employing
microchannels, and membrane micro-valves available from TMP of
Enscheda, Netherlands, and thin-walled compliant plastic
structures, micro-fluidic circuits, silicone button pneumatic
actuators and micro-valves as disclosed by Lawrence Livermore
National Laboratory at the Jul. 15-16, 1999 Knowledge Foundation
conference on Novel Microfabrication Options for Biomems, in San
Francisco, Calif., are but a few of other MEMS devices that may be
incorporated into the MEMS cassette of the present invention.
[0097] As noted earlier, the MEMS cassette may include macro-scale
valves, for example, as used in the Baxter Amicus.RTM. separator
for controlling flow through the fluid circuit module sets. These
valves and their operation is described in more detail in
previously cited U.S. Pat. No. 5,462,416. However, the MEMS
cassette may also employ MEMS-scale valves 141, as illustrated in
FIG. 7a.
[0098] A wide variety of MEMS-scale valves are available. For
example, FIGS. 15a and 15b show a bi-stable valve 156 employing a
membrane 158 that flexes between a closed position, blocking inlet
passageway 160 as shown in FIG. 15a and an open position as shown
in FIG. 15b allowing flow between the inlet passageway and outlet
passageway 162. The valve presumably opens when the pressure in the
valve chamber exceeds a threshold amount, at which time the
membrane moves from the stable closed position to the stable open
position. The valve moves to the stable closed position when the
pressure in the valve chamber drops below a certain threshold
value, causing the membrane to move from the stable open position
to the stable closed position. Such a bistable microvalve was
described by the Institute for Mikrostukturtechnik, at the July,
1999 "Novel Microfabrication Options for Biomems, Technologies
& Commercialization Strategies" conference sponsored by the
Knowledge Foundation. This is but one example of a MEMS scale valve
that may be used in the MEMS cassette. It is also known to use
micro-channels and surface tension to form MEMS scale valves, with
the valve opening when fluid pressure exceeds a certain threshold
to overcome the effects of surface tension. Such valves may also
find use in a MEMS cassettes of the type disclosed here.
[0099] An alternative design for the MEMS carrier or cassette and
the cassette reader/controller is shown in FIGS. 9-11. As shown in
FIG. 9, a cassette reader/controller 164 comprises a pair of
upstanding walls 166 defining a MEMS cassette-receiving slot
between them. One wall has a function similar to the base 100 of
the prior embodiment and the other wall fun ctions in a manner
similar to the door of the prior embodiment. In other words, one
wall includes an array of light emitting fibers, diodes or the
like, and any appropriate electrical contacts for cooperation with
the MEMS devices in the MEMS cassette. The facing wall includes an
array of light receivers for cooperating with the MEMS sensors and
for reading the characteristics sensed. As before, one of these
upstanding walls may also include macro-scale valves for actuating
or controlling flow through the MEMS cassette, or the MEMS cassette
may include MEMS-scale valves for controlling fluid.
[0100] FIG. 10-11 depicts an alternative MEMS cassette 168 for use
with reader/controller 164. The MEMS cassette 168 includes a base
170 having preformed fluid passageways 172 and pre-formed MEMS
receiving or mounting areas 174 that may be connected to the
passageways as desired for allowing fluid flow from the passageway
to the MEMS sensor. As may be seen in FIG. 10, the three fluid
pathways extend fully through the base from inlets 176 to outlets
178. A clear 180 cover is mounted on one side of the base and a
flexible membrane 182 on the other side of the base.
[0101] As shown in an underside view, in FIG. 11, valve module
areas 184 are provided in the cassette which may be opened or
closed by macro-scale valve members which depress the flexible
membrane to contact and close against a valve module to block flow
between the passageway and MEMS device or, upon release, to open a
particular valve module to fluid flow. The valve opening and
closing arrangement is preferably comparable to that already
employed in the Baxter Amicus.RTM. centrifuge, which is described
in detail in the U.S. Pat. No. 5,462,416.
[0102] As illustrated in FIG. 12, this alternative embodiment of
the MEMS reader 164 and cassette 168 permits very easy loading of
the cassette during installation of the disposable by sliding the
cassette downwardly between the upstanding walls 166 of the MEMS
cassette reader/controller.
[0103] FIG. 16 illustrates another embodiment of a MEMS cassette or
carrier 186 in accordance with the present invention. The earlier
described cassettes rely on pressure within the tubing set (created
by peristaltic pumps 92) for moving the selected fluid into and
through the MEMS cassette. However, the MEMS cassette may itself
have pumping chambers for moving fluid through the cassette and,
indeed, through the tubing set, if desired. FIG. 16 shows such a
MEMS cassette 186.
[0104] As illustrated in FIG. 16, MEMS cassette 186, comparable to
previously described embodiments, includes three internal
passageways 188 communicating with inlet flow tubing for sensing
initial condition, in-process and final condition characteristics.
In the FIG. 16 embodiment, however, each passageway also
communicates with a respective pumping chamber 190. The pumping
chamber preferably has one wall defined a flexible membrane bonded
to one side of the cassette. Flexing of the membrane by mechanical
or pneumatic pressure alternatively reduces and increases the size
of the chamber, resulting in a pumping action. Inlet and cutlet
valves 192 at each end of the pumping chamber, which are
alternatively opened and closed, control the direction of flow
through the pump. As pointed out earlier, this pumping may be used
only to move the desired fluid through the MEMS cassette or may
also be used to move fluid through the entire disposable fluid
circuit, if desired.
[0105] FIG. 18a shows a blood component container 194 with a MEMS
sensor 196 carried by or embedded in the wall of the container for
sensing a selected characteristic of the blood component in the
container. The MEMS sensor may be adapted to access the container
contents through a frangible part of the container wall or through
a piercing member associated with the sensor, and may be adapted to
test for bacterial contamination and/or pH of the stored blood
component. This would have particular application in sensing the
blood component just before administration to a patient to assure
that the pH and bacteria levels are acceptable.
[0106] After a suitable assay period required by the MEMS sensor,
the results may be read directly from the MEMS sensor.
Alternatively, the MEMS sensor may be read by a reader 198 such as
an automated optical, magnetic or electronic device, suitable for
the particular MEMS sensor mounted on the bag.
[0107] Although described in terms of one or more specific
embodiments, the present invention is not limited to the specific
structures disclosed for illustrative purposes, and includes such
changes or modifications as may be apparent to one skilled in the
field upon reading this description.
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