U.S. patent application number 09/766740 was filed with the patent office on 2002-07-25 for magnetically-actuated micropump.
Invention is credited to Singh, Angad.
Application Number | 20020098097 09/766740 |
Document ID | / |
Family ID | 25077385 |
Filed Date | 2002-07-25 |
United States Patent
Application |
20020098097 |
Kind Code |
A1 |
Singh, Angad |
July 25, 2002 |
Magnetically-actuated micropump
Abstract
A microfluidic pump having a substrate with a pump chamber and
at least one channel in communication with the pump chamber for
transporting a substance into or out of the pump chamber. A
flexible diaphragm overlies the pump chamber, and a magnetic member
is attached to the diaphragm. A magnet, such as an electromagnet,
is positioned to attract and repel the magnetic member, thereby
actuating the diaphragm, and causing a substance to be drawn into
or out of the channel. A uni-directional or bi-directional check
valve can be positioned in the channel to prevent backflow into the
pump chamber. A control system can be coupled to the pump to adjust
actuation rate of the diaphragm.
Inventors: |
Singh, Angad; (San Antonio,
TX) |
Correspondence
Address: |
Mary Jo Bertani
SKJERVEN MORRILL MACPHERSON LLP
Suite 700
25 Metro Drive
San Jose
CA
95110
US
|
Family ID: |
25077385 |
Appl. No.: |
09/766740 |
Filed: |
January 22, 2001 |
Current U.S.
Class: |
417/413.1 ;
417/413.2 |
Current CPC
Class: |
B01L 2200/143 20130101;
B01L 3/5027 20130101; B01L 7/52 20130101; B01L 2300/0816 20130101;
B01L 3/50273 20130101; B01L 2400/0605 20130101; B01L 2400/0638
20130101; B01L 2400/0439 20130101; B01L 2200/10 20130101; F04B
43/046 20130101; B01L 2400/0481 20130101 |
Class at
Publication: |
417/413.1 ;
417/413.2 |
International
Class: |
F04B 017/00 |
Claims
What is claimed is:
1. A microfluidic pump comprising: a substrate including a chamber;
at least one channel in communication with the chamber; a flexible
diaphragm forming a wall of the chamber; and a magnetic member
attached to the diaphragm.
2. The pump of claim 1 further comprising: a check valve positioned
in the channel.
3. The pump of claim 2 wherein the check valve is
unidirectional.
4. The pump of claim 2 wherein the check valve includes a flap
having one end movably attached to one sidewall of the channel.
5. The pump of claim 1 further comprising an electromagnet
positioned to attract and repel the magnetic member.
6. The pump of claim 5 further comprising: a current source coupled
to supply electric current to the electromagnet.
7. The pump of claim 6 further comprising: a control system coupled
to adjust the current output by the current source.
8. The pump of claim 1 further comprising a protective layer
covering the top of the diaphragm.
9. The pump of claim 1 further comprising a protective layer
covering the bottom of the substrate.
10. The pump of claim 5 wherein the electromagnet is positioned
adjacent the magnetic member.
11. The pump of claim 5 wherein the electromagnet is positioned
separate from the magnetic member.
12. A microfluidic pump comprising: a substrate including a pump
chamber; at least one channel in communication with the pump
chamber; a flexible diaphragm overlying the pump chamber; and means
for actuating the flexible diaphragm.
13. The pump of claim 12 wherein the means for actuating the
flexible diaphragm includes an electromagnet.
14. The pump of claim 12 wherein the means for actuating the
flexible diaphragm includes a permanent magnet.
15. The pump of claim 13 further comprising: a current source
coupled to supply electric current to the electromagnet.
16. The pump of claim 15 further comprising: a control system
coupled to adjust the current output by the current source.
17. The pump of claim 12 further comprising: a check valve
positioned in the channel.
18. The pump of claim 12 wherein the substrate is a polymer
material.
19. The pump of claim 12 wherein the substrate is injection
molded.
20. The pump of claim 12 wherein the channel and the pump chamber
are embossed in the substrate.
21. A system for transporting a substance, the system comprising: a
substrate including a pump chamber; at least one channel in
communication with the pump chamber; a flexible diaphragm forming a
wall of the pump chamber; means for actuating the flexible
diaphragm; and a control system coupled to control the means for
actuating the flexible diaphragm.
22. The system of claim 21 wherein the means for actuating the
flexible diaphragm includes an electromagnet.
23. The system of claim 21 wherein the means for actuating the
flexible diaphragm includes a permanent magnet.
24. The system of claim 22 further comprising: a current source
coupled to supply electric current to the electromagnet.
25. The system of claim 21 further comprising: a check valve
positioned in the at least one channel.
26. The system of claim 21 wherein the substrate is a polymer
material.
27. The system of claim 21 wherein the substrate is injection
molded.
28. The system of claim 21 wherein the channel and the pump chamber
are embossed in the substrate.
29. A method for transporting a substance using a pump system,
wherein the pump system includes a chamber, at least one channel in
communication with the chamber, a flexible diaphragm forming a wall
of the chamber, and a magnetic member attached to the diaphragm,
the method comprising: attracting the magnetic member to cause the
substance to flow into the chamber; and repelling the magnetic
member to cause the substance in the chamber to flow out of the
chamber.
30. The method of claim 29, wherein the pump system further
includes a check valve positioned in the channel, the method
further comprising: opening the check valve while attracting the
magnetic member; and closing the check valve while repelling the
magnetic member.
31. The method of claim 30 wherein the check valve is
unidirectional.
32. The method of claim 30 wherein the check valve includes a flap
having one end movably attached to one sidewall of the channel.
33. The method of claim 29, wherein the pump system further
includes an electromagnet positioned to attract and repel the
magnetic member, the method further comprising: adjusting current
supplied to the electromagnet to control attracting and repelling
the magnetic member.
34. A method of fabricating a pump system for transporting a
substance, the method comprising: forming a pump chamber in a
substrate; positioning at least one channel in communication with
the pump chamber; forming at least a portion of a wall of the pump
chamber with a flexible diaphragm; and attaching a magnetic member
on the flexible diaphragm.
35. The method of claim 34 further comprising: positioning a magnet
to attract and repel the magnetic member.
36. The method of claim 34, wherein the magnet is an electromagnet,
the method further comprising coupling a control system to control
current to the electromagnet.
37. The method of claim 34 further comprising: positioning a check
valve in the at least one channel.
38. The method of claim 34 further comprising: using a polymer
material for the substrate.
39. The method of claim 34 further comprising: injection molding
the substrate.
40. The method of claim 34 further comprising: embossing the pump
chamber in the substrate.
41. The method of claim 34 further comprising: positioning a
protective layer over the pump system.
42. The pump of claim 34 further comprising: positioning a
protective layer under the pump system.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is related to and incorporates by reference
herein in its entirety the commonly owned and concurrently files
patent application Attorney Docket Number M-9289 entitled
"AUTOMATED MICROFABRICATION-BASED BIODETECTOR" by Angad Singh and
Shahzi S. Iqbal.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates generally to micropumps. More
specifically, this invention relates to a micropump that is
magnetically actuated.
[0004] 2. Description of the Related Art
[0005] There are several applications that require pumps for
transporting substances from one location to another. Some of these
applications include medical implants, miniature scrubbing systems,
chemical analysis of very small samples, and medical diagnosis.
Pumps having nanometer-scale dimensions are required in some of
these situations. Microfabrication techniques are well-known in the
art, and are capable of producing very small scale components with
moving parts. It is nonetheless desirable to provide a micropump
that is capable of delivering the appropriate amount of a substance
using a minimum number of moving parts to simplify fabrication.
SUMMARY OF THE INVENTION
[0006] A pump (also called "microfluidic pump") in accordance with
the invention has a substrate with a chamber (also called "pump
chamber") and at least one channel in communication with the pump
chamber for transporting a substance into or out of the pump
chamber through one or more channels. A flexible diaphragm forms a
wall of the pump chamber, and the pump operates when the diaphragm
is flexed.
[0007] In one embodiment, a magnetic member is attached to the
diaphragm. A magnet, such as an electromagnet, is positioned to
attract and repel the magnetic member, thereby actuating the
diaphragm, and causing a substance to be drawn into or out of the
pump chamber through the channel. Depending on the embodiment, a
uni-directional or bi-directional check valve can be positioned in
the channel to allow flow of the substance into the chamber or to
prevent backflow into the pump chamber. Also depending on the
embodiment, a control system can be coupled to the pump to sense
the flow rate of the substance in the channel, and to adjust
actuation rate of the diaphragm based on the flow rate. Moreover,
as an option, a protective layer can be included to cover the top
of the diaphragm. Another protective layer can be included to cover
the bottom of the substrate.
[0008] Depending on the implementation, the substrate and diaphragm
can be fabricated with polymer materials that are injection molded,
etched, or embossed with the components such as the chamber,
channels, and valves.
[0009] The present invention advantageously provides a micropump
with a minimum number of moving parts to improve reliability and
cost-effectiveness. The micropump is also decoupled from the
actuating mechanism. The advantage of this feature is that the pump
can be included in a disposable portion of a system, while the
actuating mechanism is included on a non-disposable portion of the
system and can be used to actuate other micropumps.
[0010] The foregoing has outlined rather broadly the features and
technical advantages of the present invention so that the detailed
description of the invention that follows can be better
understood.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a block diagram of components included in an
embodiment of a bio-sensor system in accordance with the present
invention.
[0012] FIG. 1a is a block diagram of components included in an
embodiment of a bio-sensor device in accordance with the present
invention.
[0013] FIGS. 1aa-1aw are schematic diagrams of circuits included in
a biosensor system in accordance with an embodiment of the present
invention.
[0014] FIG. 1b is a top view of components included in an
embodiment of a bio-sensor device in accordance with the present
invention.
[0015] FIG. 1c is a side cross-section view of components included
in an embodiment of a bio-sensor device in accordance with the
present invention.
[0016] FIG. 2 is a block diagram of components included in an
embodiment of a microfluidic system for the bio-sensor in
accordance with the present invention.
[0017] FIG. 2a is a flowchart of protocols for detecting viruses,
bacteria, and toxins using a bio-sensor system in accordance with
the present invention.
[0018] FIG. 3a is a side of view of a filtration/concentration
assembly in accordance with the present invention.
[0019] FIG. 3b is a side of view of a portion of the
filtration/concentration assembly that is used to introduce a
sample to a microfluidic system in accordance with the present
invention.
[0020] FIG. 3c is a side of view of the electro-magnetically
actuated pump in accordance with the present invention.
[0021] FIG. 3d is a top view of the electro-magnetically actuated
pump and check valve in accordance with the present invention.
[0022] FIG. 3e is a block diagram of a microfluidic pump coupled to
a feedback and control system in accordance with the present
invention.
[0023] FIG. 3f is a block diagram of a piezoelectric pump coupled
to a feedback and control system in accordance with the present
invention.
[0024] FIG. 3g is a diagram of a mixer in accordance with the
present invention.
[0025] FIG. 4 is a diagram of an information network in accordance
with the present invention.
[0026] The present invention may be better understood, and its
numerous objects, features, and advantages made apparent to those
skilled in the art by referencing the accompanying drawings. The
use of the same reference symbols in different drawings indicates
similar or identical items.
DETAILED DESCRIPTION
[0027] Referring to FIG. 1, biosensor system 100 is shown including
bio-sensor device 102, microfluidic system 104, and network
interface 106 to workstation 108. In one embodiment, microfluidic
system 104 incorporates components that are required for performing
chemical and/or biological processes on a sample of a substance to
be analyzed. Microfluidic system 104 can be inserted and removed
from biosensor device 102. Biosensor device 102 is a portable,
hand-held unit that includes a user interface and display, an
interface to microfluidic system 104, and an network interface 106
to one or more workstations 108 that allows a user at workstation
108 to access data collected using biosensor system 100. Biosensor
system 100 can also be used as a workstation 108.
[0028] Referring now to FIGS. 1 and 1a, a block diagram of one
embodiment of biosensor device 102 is shown in FIG. 1a. Power
supply 110 provides operating power to various components on
biosensor device 102 including digital signal (DSP) and
input/output (I/O) processor 112, driver circuits 114, analog
circuits 116, a display 118, valves 120, thermistor 122,
thermo-electric cooler 124, pump coils 126, and detection system
128. Power supply 110 can be one or more commercially available
power supplies, such as an internal DC battery or a power regulator
that interfaces to an external AC supply. Power supply 110 is
capable of providing one or more operating voltages at the levels
required by the components of biosensor device 102. Biosensor
device 102 can also be powered via a universal serial bus (USB)
port 130 with the workstation 108.
[0029] In the embodiment shown in FIG. 1a, data processing
functions are divided among DSP and input/output (I/O) processor
112, driver circuits 114, and analog circuits 116. It is important
to note, however, that data processing functions can be distributed
using additional or fewer processors than shown in FIG. 1a. FIGS.
1aa through 1aj are schematic diagrams showing examples of
interface circuits between DSP 131 and components in DSP and I/O
processor 112. FIG. 1ab shows an example of an interface to
programmable memory 140 for storing DSP program instructions. FIG.
1ac shows an example of an interface to Analog to Digital converter
ADC 148 which converts analog voltage level (e.g., temperature
& fluorescence level) to a digital signal which can be used by
the DSP. FIG. 1ad shows an example of an interface to digital to
analog signal converter DAC 146 which provides analog output
voltage. FIG. 1ae shows an example of an interface to memory 142
for non-volatile memory storage. FIG. 1af shows an example of an
interface to RS-232 serial interface 133. FIG. 1ag shows an example
of an interface to device indicators 144. FIGS. 1ah and 1aj show
examples of an interface to digital I/O 150, which also interfaces
with the driver circuits 114. FIG. 1ai shows an example of an
interface to USB port 130.
[0030] FIG. 1ak is an example of a schematic on analog circuits
board 116 of a programmable amplifier that can be used to amplify
the signal from the photo-multiplier-tube (PMT) 184.
[0031] FIGS. 1al through 1aw show examples of schematics for driver
circuits 114. FIG. 1al shows an example of a programmable duty
cycle generator for controlling the amount of power to TEC 124.
FIG. 1am shows an example of a DC to DC converter which conditions
power supply voltage. For example, the circuit in FIG. 1am converts
a +12 volt (V) supply voltage to +5V, +12V and regulated +12V. FIG.
1an shows an example of an interface between DSP and I/O circuits
112, analog circuits 116, and driver circuits 114.
[0032] FIGS. 1ao and 1ap show examples of circuits which provide a
set of digital control output signals for opening and closing,
respectively, valves 120. FIG. 1aq shows an example of a light
emitting diode to indicate when power to the system 100 (FIG. 1) is
turned ON. FIG. 1ar shows an example of a circuit for a
piezoelectric buzzer for chip insert detection or user input
detection. FIG. 1 shows an example of an interface connector for
connecting DSP 131 to other components in DSP and I/O processor
112.
[0033] Biosensor system 100 also includes bridge circuits, examples
of which are shown in schematics in FIGS. 1at through 1aw. FIG. 1at
is an example of circuit for controlling TEC 124 (FIG. 1a). FIG.
1au is a bridge circuit used for controlling the current through
the pump coil(s) 126 (FIG. 1a). FIG. 1av is a laser diode driver
circuit which maintains a constant light output from the laser 182
(FIG. 1a) by regulating the current to the laser. FIG. 1aw is an
example of a connector 152 which can be used to interface the
microfluidic system 104 to biosensor device 102.
[0034] Examples of commercially available components which are
suitable for use in the circuits shown in FIGS. 1aa through 1aw are
as follows: FIG. 1aa: DSP chip ADSP-2181, part # ADSP-2181KS-115 by
Analog Devices, Norwood, Mass.; FIG. 1ab: EEP ROM (memory) chip,
part # CAT28F512 by Catalyst Semiconductor, Sunnyvale, Calif.; FIG.
1ac: Analog-to-digital converter chip, part # AD7887 by Analog
Devices, Norwood, Mass.; FIG. 1ad: Digital-to-analog converter
chip, part # AD5322 by Analog Devices, Norwood, Mass.; FIG. 1ae:
EEPROM (memory) chip, part # 24LC256 by Microchip Technology,
Farmington Hills, Mich.; FIG. 1af: RS-232 chip, part #DS14C232 by
Dallas Semiconductor, Dallas, Tex.; FIG. 1ag: demultiplexer chip,
part # MC74HC138 by ON Semiconductor, Phoenix, Ariz.; FIG. 1ah:
Digital output gates and flip-flop chips, part #s MC74HC32 and
MC74HC574 by ON Semiconductor, Phoenix, Ariz.; FIG. 1ai: USB
interface chip, part # PDIUSBD12D by Phillip Semiconductor,
Sunnyvale, Calif., and gate 74HC08 by ON Semiconductor, Phoenix,
Ariz.; FIG. 1aj: flip-flop and gate chips, part #s MC74HC573 and
MC74HC32 respectively by ON Semiconductor, Phoenix, Ariz.; FIG.
1ak: Programmable gain amplifier chips, part # PGA103 by Burr-Brown
Corporation/Texas Instruments, Dallas, Tex., and operational
amplifier OP27 by Analog Devices, Norwood, Mass.; FIG. 1al: Shift
registers, part #74HC165 by ON Semiconductor, inverters, part
#74HC14 and #74HC04 by ON Semiconductor, Phoenix, Ariz.; FIG. 1am:
DC-DC converter chips COSEL_ZU, part # ZUS 1R5 1205 by Cosel USA,
San Jose, Calif. and AA01D_DUAL, part # AA01D-012L-120D by Astec
America, Carlsbad, Calif.; FIG. 1ao: Flip-flop, part # 74HC574 by
ON Semiconductor, and gate 74HC32 also by ON Semiconductor,
Phoenix, Ariz.; FIG. 1ap: Same as FIG. 1ao; FIG. 1at: Gates, part
#74HC14 and part #74HC08 by ON Semiconductor, Phoenix, Ariz.; FIG.
1au: Same as FIG. 1at; FIG. 1av: inverters, part # 74HC14 by ON
Semiconductor, and laser diode driver, part # iC-WJ by iC-Haus,
Bodenheim, Germany.
[0035] Microfluidic system 104 includes microfabricated components
for performing biological and chemical analysis. Such components
can include, for example, filters, valves, pumps, mixers, channels,
reservoirs, and actuators. Detection system 128 is used to detect
target molecules that are the subject of the assay(s) that are
performed using microfluidic system 104. One such detection system
128 includes an infrared (IR) laser and detector which is used to
illuminate and detect IR dye, respectively, known as
deoxynucleotide triphosphates (dNTPs) that can be used in the
assays performed by microfluidic system 104. Other suitable
detection systems can be implemented with microfluidic system 104
in addition to, or instead of, an IR detection system. Detection
system 128, and microfluidic system 104 are discussed more fully
hereinbelow.
[0036] In one embodiment, microfluidic system 104 is disposable and
can be inserted and removed from biosensor device 102 as required.
This allows a new microfluidic system 104 to be used for each new
sample to be analyzed, thereby reducing the risk of contamination
from previous samples.
[0037] DSP and I/O processor 112 includes a digital signal
processor 131 for digital signal processing along with main program
instructions 132 that control execution of components included in
processor 112. Main program instructions 132 also control
communication with components external to processor 112. In one
embodiment, digital signal processor 131 is a single-microfluidic
system 104 microcomputer optimized for digital signal processing
(DSP) and other high speed numeric processing applications. Digital
signal processor 131 includes one or more serial data interfaces
such as RS2-32 interface 133 and Universal Serial Bus (USB)
interface 130. A peripheral device interconnect USB 134 shown, for
example, as PDIUSBD12, allows conventional peripherals to be
upgraded to USB devices and take advantage of the "hot plug and
play" capability of the USB, as known in the art. The USB 134
interfaces with most device class specifications such as imaging,
mass storage, communications, printing and human interface devices.
USB 134 communicates with digital signal processor 131 using a
high-speed, general-purpose parallel interface 138. Other data
interfaces can be included in addition to or instead of interfaces
133 and 134.
[0038] Digital signal processor 131 also interfaces with other
devices well-known in the art, including program and data memory
140, 142 for storing data and executing program instructions,
device indicators 144, such as switches and lights, digital to
analog (DAC) and analog to digital (ADC) converters 146, 148, and
digital I/O controller 150. Digital signal processor 131 can also
include a programmable timer and interrupt capabilities, as known
in the art. Power-down circuitry can also be provided to conserve
power when operating biosensor device 102. One example of a
microprocessor currently available that is suitable for use with
present invention is model number ADSP-2181 manufactured by Analog
Devices, Inc. in Norwood, Mass.
[0039] Driver circuits 114 interface with microfluidics system 104
via connector 152 to communicate with valves 120, thermistor 122,
thermoelectric cooler (TEC) 124, pumps 126. Driver circuits 114
also interface with detection system 128 in biosensor device 102.
Connector 152 can be one of several connectors that are well known
in the art and commercially available. One such connector is part #
FH12-50S-0.5SH by Hirose Electric Co. Ltd.
[0040] Driver circuits include thermistor driver 153 and TEC driver
154 which generate signals to control the operation of thermistor
122 and TEC 124, respectively. Pump driver 156 includes logic to
determine voltage signals required to operate pumps 126. The
signals input to microfluidic system 104 to drive pumps 126 can be
based on information provided by flow sensors 157 microfluidic
system 104, wherein the sensors 157 indicate the amount or rate of
flow of a substance through one or more pumps 126. Laser driver 158
generates signals to control operation of a laser in detection
system 128. Such a laser is used for fluorescence detection, as
further discussed hereinbelow.
[0041] Insert detector 162 receives information from microfluidic
system 104 that indicates when microfluidic system 104 is inserted
in biosensor device 102. When microfluidic system 104 is inserted
in biosensor device 102, processors 112, 114, and 116 use the
signal to begin operating other components in biosensor device
102.
[0042] Valve driver 164 sends signals to open and close valves 120
microfluidic system 104. A variety of valve and pump configurations
can be implemented in microfluidic system 104, depending on the
processes to be performed. The processes typically occur in a
particular sequence, and can also be timed. Thus, valve driver 164
includes instructions for opening and closing each valve in
microfluidic system 104 for respective processes and reactions.
Valve driver 164, pump coil driver 156, thermistor driver 153, TEC
driver 154, and laser driver 158, can also share information to
determine which functions to perform at the appropriate time.
[0043] User interface (UI) module 168 provides information and/or
options to a user that is presented on display 118 and via device
indicators 144. UI module 168 also receives input from one or more
of a variety of known user input devices such as a keyboard, mouse,
light pen, audio commands, or other data input device known in the
art. It is important to note that a variety of suitable user input
devices and displays, including audio, visual, and tactile
input/output devices, are known in the art and can be incorporated
with the present invention. The foregoing examples are not intended
to limit the present invention to any particular input or display
device, or combination of devices.
[0044] Detection system 128 generates data signals representing the
substances detected microfluidic system 104, and the data signals
are input to analog circuits module 116. Analog circuits module 116
includes appropriate signal conditioning components 174, as
required, such as a sample and hold circuit, filter(s), and/or an
amplifier(s). The output from analog circuits module 116 is input
to an analog to digital (A/D) converter 148 in DSP and I/O
processor 112 for conversion from analog to digital form. This
digital data can be further processed in DSP and I/O processor 112,
and the results output to display 118 and/or network interface
106.
[0045] A variety of processes are required to perform different
biological and chemical assays. For example, detecting a particular
biological or chemical agent in a sample can include distilling and
purifying a sample, heating the sample, mixing the sample with
various reactants, and filtering the treated sample to isolate the
target agent. Biosensor device 102 provides signals to actuate
valves, pumps, and mixers to control the flow and mixing of the
sample and various reactants to and from reservoirs in microfluidic
system 104. Biosensor device 102 also provides control signals to
thermistor driver 153 and TEC driver 154, which in turn provide
signals to control operation of thermistor 122 and TEC 124,
respectively, during processes such as DNA/protein denaturation,
single strand DNA annealing, and primer extension. Biosensor system
102 can be programmed to perform a variety of assays that are
performed automatically, or when selected by a user through UI
module 168.
[0046] DSP and I/O processor 112, driver circuits 114, and analog
circuits 116 in biosensor device 102 can be implemented using a
combination of hardware circuits, software, and firmware, as known
in the art.
[0047] One application of biosensor device 102 is automating PCR
analysis. Nano-scale devices for automating PCR and post-PCR
analysis are available in the prior art, however, sample
preparation including DNA/RNA isolation, and detection by PCR are
still carried out manually as two different processes. Therefore,
to fully exploit the potential of PCR-based detection, biosensor
device 102 advantageously integrates sample preparation, target
amplification, and fluorescence detection into a single, portable,
cost-effective device. Biosensor device 102 can also be used for
biological and chemical analysis processes in addition to, or
instead of, PCR-based analysis.
[0048] Referring now to FIGS. 1, 1a, 1b, and 1c, FIGS. 1b and 1c
show a top view and side cross-sectional view of components of
biosensor system 100 with microfluidics system 104 inserted into
the biosensor device 102. Electronic circuit cards 180 control the
operation of the optics in biosensor system 100, including laser
diode source 182 and photo-multiplier tube (PMT) 184. In an
alternate implementation, any other light source, such as a blue
LED, can be used instead of, or in addition to, laser diode source
182. Photodiode(s), or any other photo or electrical signal
detection system, can be used, instead of, or in addition to,
photomultiplier tube 184 for fluorescence detection and/or
measurement. Electronic circuit cards 180 also include DSP and I/O
processor 112, driver circuits 114, and analog circuits 116.
[0049] There are a variety of different detection systems 106 that
can be implemented in biosensor device 102. One such detection
system 128 that can be implemented in biosensor 100 is shown in
FIGS. 1b and 1c. Detection system 128 includes optical components
such as mirrors 185, 186, diachroic filter 188, and objective
lenses 190, 192. Incident light beams (excitation) from laser diode
182 pass through a diachroic filter 188 and are directed at a
specific wavelength via a mirror 185 and an objective lens 190 in
respective order, to the detection area on the microfluidic system
104. Reflected (emitted) light beams from the detection area on the
microfluidic system 104 are directed via the objective lens 190,
mirror 185, diachroic filter 188 and mirror 186 at a specific
wavelength, in respective order, to the detector 184, i.e.,
photomultiplier tube/photodiode. Emitted fluorescence (reflected
light) is sensed by the detector 184, i.e., photomultiplier
tube/photodiode. Detector 184 generates data signals representing
the emitted (reflected) light and the data signals are input to
analog circuits 116 (FIG. 1) for signal conditioning and conversion
from analog to digital signals.
[0050] Microfluidic system 104 is inserted into biosensor device
102 and is guided to the appropriate position by one or more guide
members 194 which slides the microfluidic system 104 into position
to connect electrical connector 152. Following insertion of
microfluidic system 104, loading lever 196 is released to allow
spring member 198 to place TEC 124 in contact with microfluidic
system 104. Additionally, electromagnetic pump coils 199 are
positioned adjacent to the top side of the microfluidic system 104.
One or more of these coils 199 can also be positioned on adjacent
other sides of microfluidic system 104 to actuate pump(s) 126.
[0051] Referring now to FIG. 2, an embodiment of microfluidic
system 104 is shown including a plurality of pumps, valves,
filters, mixers, reservoirs, and channels as described below.
Connector 152 is also shown in microfluidic system 104, however the
connections between the connector 152 and other components on
microfluidic system 104 are not shown for simplicity. The
connections between connector 152 and the other components are used
to communicate signals such as drive signals and detection
signals.
[0052] Note that the components shown and their placement with
respect to one another in FIG. 2 depends on the particular
processes to be performed using biosensor device 102. Notably, the
number of components and their position with respect to one
another, can vary from the configuration shown in FIG. 2. Other
types of components can be included in addition to those shown in
FIG. 2. Microfluidic system 104 can be configured with enough
components to perform one or more protocols concurrently, or at
different times with respect to one another. Further, some
applications may not require the use of all the components in a
given configuration. For example, a particular configuration of
microfluidic system 104 can be used for more than one type of
process. In this situation, one or more of the reservoirs may be
used in some of the processes, but not in others due to different
steps being required to prepare and process the sample.
Additionally, the components, operate independently of one another,
and can be controlled by an external or an embedded control
system.
[0053] Components can be included in microfluidic systems 104 to
perform processes to detect genes, toxins, viruses, bacteria, and
vegetative cells. Microfluidic system 104 is intended to include
most, if not all, of the components required to perform the process
from start to finish, and thus minimal user handling of the sample
and intervention is required. Microfluidic system 104 is also
designed to be low-cost and hence disposable. These features
advantageously lower the risk of contaminating the sample during
testing. Further, microfluidic system 104 yields highly
reproducible results while requiring a relatively small sample
size. For example, a 2.25 square inch disposable microfluidic
system 104 can accommodate a sample volume of 500-1000 microliters
(before concentration) and a concentrated sample volume of 10
microliters.
[0054] In some situations, a sample can contain a low concentration
of molecules to be detected. In some embodiments, the dimensions of
microfluidic system 104 can range from one to two inches in length
and height, and be less than one millimeter in thickness. Due to
the small size of microfluidic system 104, the sample may need to
be filtered and concentrated prior to performing the extraction and
detection processes.
[0055] Referring to FIG. 2, a sample containing varying amounts of
targets, i.e., cells, virions, or toxins, can be loaded in sample
entry port 202 and subjected to a respective sample preparation
procedure, such as concentration. This is accomplished by inputting
the sample into filter 204 to remove impurities that are larger in
size than the target cells, viruses, or concentrates in the
sample.
[0056] FIG. 2a shows a flowchart of examples of protocols that may
be implemented on microfluidic system 204 (FIG. 2), including
bacteria protocol 260 for isolating and purifying DNA from
bacterial cells, virus protocol 262 for isolating and purifying RNA
from animal viruses, and toxin protocol 264 for isolating and
purifying toxins. Protocols 260, 262, and 264 are representative of
the types of assays that can be performed on an appropriately
configured microfluidic system 104.
[0057] Referring to FIGS. 2 and 2a, once the sample is introduced
to microfluidic system 104, DNA/RNA purification that is used in
protocols 260 and 262 can be achieved as described in the following
steps:
[0058] 1. The sample is transferred to chamber 208 by actuating
pump 206, which can be a push button pump or an electronically
actuated pump.
[0059] 2. The sample is mixed/resuspended in lysozyme solution from
reservoir 210, which is transferred to mixer 208 via actuation of
pump 212.
[0060] 3. A chamber in mixer 208 is heated to 95 degrees centigrade
for a period of time, for example, 2 minutes.
[0061] 4. Protease (e.g. Proteinase K) in reservoir 214 is pumped
into mixer 208 via pump 215.
[0062] 5. The lysed sample is pumped through microfilter 216 into
mixer 220 via pump 218. In one implementation, microfilter 216 is a
one to two micrometer filter. In other implementations, the size of
microfilter 216 is selected based on the size of the target
molecule.
[0063] 6. A DNA wash solution (for example, Ethanol and salts
buffer) is transferred from reservoir 224 to mixer 220 via pump
228.
[0064] 7. The sample+DNA wash solution from mixer 220 is pumped to
the wash discard reservoir 232 via pump 234 through a microfilter
230 or a nucleic acid binding agent such as glass milk.
[0065] 8. Steps 6 and 7 can be repeated to concentrate DNA/RNA at
the microfilter 230 or nucleic acid binding agent, and to discard
proteins as well as other contaminants.
[0066] 9. Aqueous solution from reservoir 222 is pumped in the
reverse direction through the microfilter 230 to the DNA/RNA
collection chamber 238 for PCR. At this point, the DNA/RNA is
dissolved in the aqueous solution and is no longer bound to
microfilter 230. Collection chamber 238 can either contain magnetic
micro-beads or a polynucleotide array with assay-specific
primers.
[0067] For toxins or antigens (protein) protocol 264 includes the
following processes:
[0068] 1. The sample is transferred to mixer 208 by actuating pump
206, which can be a push button pump or an electronically actuated
pump.
[0069] 3. The toxin sample is mixed/resuspended in lysozyme
solution from a reservoir such as 210, which is transferred to
chamber 208 via actuation of pump 212.
[0070] 4. Protease inhibitor from a reservoir such as 214 is pumped
into the lysis chamber 208 via pump 215.
[0071] 5. The sample is pumped through microfilter 216 into mixer
220 via pump 218.
[0072] 6. A basic pH wash solution (for example, 0.1M
Na.sub.2CO.sub.3 buffer, pH=9.0) is transferred from reservoir 224
to mixer 220 via pump 228.
[0073] 7. The sample+wash solution from mixer 220 is pumped to the
wash discard reservoir 232 via pump 234 through a cationic
microfilter 230 or a protein binding agent such as cationic
beads.
[0074] 8. Steps 6 and 7 can be repeated to concentrate the toxin
(protein) at the microfilter 230 or protein binding agent, and to
discard nucleic acid as well as other contaminants and cell
debris.
[0075] 9. Neutral pH buffer solution (such as PBS pH=7.4 containing
1M NaCl), from reservoir 222 is pumped through the cationic
microfilter 230 to the protein collection chamber 238 for
immuno-PCR. At this point, the protein is dissolved in the neutral
buffer and is no longer bound to the microfilter 230 or the protein
binding agent. In the collection chamber the toxin is mixed with
the respective antibodies conjugated with specific primers and
allowed to bind at 37 degrees centigrade for a period of time, such
as 5 minutes. The treated sample is transferred from the chamber
208 to the collection chamber 238 (PCR area) where a target bound
to an antibody is captured for PCR-based signal amplification
reaction and waste is discarded in reservoir 232. The collection
chamber 238 can either contain magnetic micro-beads or a
polynucleotide array with millions of assay-specific primers
anchored to the surface.
[0076] In one embodiment, millions of copies of the primers can be
anchored on magnetic beads, such as those available from Bangs
Laboratories, Inc. in Fishers, Ind. The target can be detected
using known conjugating methods, such as streptavidin-biotin
capture methods. Additionally, for high throughput amplification,
an identical set of primers can also be supplied free in solution
along with PCR reagents.
[0077] After the target is extracted, purified, and captured in the
collection chamber 238, the target is denatured at 95 degrees
centigrade, and allowed to anneal (hybridize) at 65.degree.
centigrade with the primers anchored to an array or magnetic
microbeads. In this step, the two strands of DNA are separated and
respective anchored primers, as well as primers free in solution
(supplied as reagent), bind to the complimentary target
sequences.
[0078] Following hybridization, enzyme DNA polymerase, such as Taq
DNA polymerase or rTth polymerase provided by, for example, PE
Applied Biosystems in Foster City, Calif., elongates or synthesizes
new complimentary strands in 5'.fwdarw.3' incorporating labeled,
i.e., fluorogenic dNTPs, at 72.degree. C. In subsequent cycles of
denaturation, annealing and elongation, newly synthesized strands
(amplicons) serve as templates for exponential amplification of the
target sequence. 3' extension of the primers anchored to the
surface leads to synthesis of fluorophore labeled target sequences
covalently bound to the surface. Fluorophore labeling is
accomplished by incorporation of fluorophore-dNTPs such as Cy5
dye-dCTP/dUTP. After removing free dNTPs and other reagents by
washing, fluorescence is measured by detection system 128 (FIG.
1).
[0079] Microfluidic system 104 can be configured and adapted to any
of the nucleic acid-based assays, i.e., target amplification and
hybridization-based signal amplification methods, as discussed in
an article entitled "A Review of Molecular Recognition Technologies
for Detection of Biological Threat Agents" by Iqbal, S. S.,
Michael, M. W., Bruno, J. G., Bronk, B. V., Batt, C. A., Chambers,
J. P., Review article (2000). Biosensors and Bioelectronics.
[0080] A microfilter that is suitable for use as filter 204 can be
fabricated by etching pillars that are spaced as closely as 1
micrometer apart in the substrate that is used as the base for
microfluidic system 104. One or more of a variety of suitable
materials can be used for the substrate, such as silicon and/or
plastic. The pillars can be created by etching a material such as
silicon, or by other processes that depend on the material being
used, such as injection molding with plastic materials. The filter
pillars can be fabricated along with the pump chambers, valves, and
mixers. To create filters with smaller pore sizes, the pillars can
be coated with a suitable material. For example, silicon pillars
can be coated with a conformal material such as
low-pressure-chemical-vapor-deposition (LPCVD) polysilicon, which
is a standard material that is well-known in microfabrication
art.
[0081] FIG. 3a shows filtration/concentration assembly 300 than can
be used instead of, or in addition to, filter 204. Assembly 300
includes a loading chamber 302, a receiving chamber 304, and a
plunger 306. Loading chamber includes a funnel portion 308 that
mates with another funnel portion 310 on receiving chamber 304 as
shown in FIG. 3a. Once loading chamber 302 and receiving chamber
304 are mated, the sample to be concentrated and filtered is
introduced in loading chamber 302. Plunger 306 can be inserted in
receiving chamber 304 and pushed downward to force the sample
through filter 312.
[0082] Filter 312 is an appropriately sized microfilter, depending
on the size of the molecule to be detected. A molecular weight cut
off filter or a negatively charged fiber glass filter such as those
commercially available from Memtec Limited, Timonium, Md., can be
used.
[0083] As the sample is pushed through filter 312, the analytes of
interest are retained and concentrated on filter 312 while the
excess solution passes through filter 312. Receiving chamber 304 is
open at the end to allow the excess solution to flow out.
[0084] Once the runoff of the excess solution is completed,
assembly 300 is disassembled, receiving chamber 304 is inverted and
a volume of assay reagent is loaded in receiving chamber 304. The
volume of assay reagent can be as low as 5 to 25 microliters,
depending on the size of port 202 in the microfluidic system 104.
Plunger 306 is inserted in the top of receiving chamber 304, and
funnel portion 310 is inserted in port 202 (FIG. 2) in microfluidic
system 104, as shown in FIG. 3b. Plunger 306 is pushed downward to
force the assay reagent though filter 312. Analytes previously
concentrated on filter 312 are dissolved in the assay reagent and
transferred into microfluidic system 104 through port 202.
[0085] Any suitable, commercially available thermal cycling device,
such as a thermo-electric cooler (TEC) 112 (FIG. 1) can be used to
heat and cool the sample as described in the steps above. Size and
power output of the TEC depends on the application. OptoTEC and
ThermaTEC series TEC's by MELCOR Corporation in New Jersey are
suitable for use in such in systems. Alternatively, resistive
heaters microfabricated on the microfluidic system 104 can be used
for heating while the TEC 124 can be used for cooling.
[0086] TEC 124 is positioned on or near microfluidic system 104
(FIG. 1) in close enough proximity to the chambers to effectively
heat or cool the fluid(s). A silver-filled heat resistant adhesive
with high thermal conductivity can be used to attach TEC 124 to
promote heat transfer. Alternatively, TEC 124 can be included in
biosensor device 102 such that it is aligned and spring-loaded to
rest in a position to heat or cool the contents of the desired
chambers microfluidic system 104 when it is inserted into biosensor
device 102.
[0087] Temperature feedback for closed-loop control is provided by
a thermocouple which is co-located with the TEC 124. Thermocouples
are a commercially available from numerous companies, for example,
Newark Electronics Corporation in Chicago, Ill. and WakeField
Engineering, Inc. in Beverly, Mass. Temperature feedback can also
be provided by microfabricated temperature sensors that are built
in to microfluidic system 104.
[0088] In one embodiment, microfluidic system 104 has a planar
design, i.e., all components can be fabricated in one step, which
eliminates the need for stacking multiple layers and simplifies
fabrication. Reservoirs can be sized according to the amount of
substance to be stored in them. Reservoirs, mixers, and pumps can
include access holes for loading sample(s) and reagents. The
sample(s) and reagents can be introduced using a syringe and the
holes can be sealed by laminating a film of a hydrophobic porous
material, such as GORE-TEX.RTM. by W. L. Gore and Associates, Inc.,
which will act as a vent for trapped gases.
[0089] A variety of materials and fabrication techniques can be
used for monolithic fabrication of the pumps and other components
of the planar system. In one embodiment, the system can etched out
in a silicon substrate using a deep anisotropic silicon etching
process known as ICP Multiplex System by Surface Technology Systems
in the United Kingdom. A flexible glass cover can then be bonded to
cover the channels and also form the diaphragm for the pumps. The
flexible cover can also include electrical interconnects for
various components in the substrate, and can be transparent to
allow optical detection or viewing under a microscope.
[0090] In another embodiment, the system can be embossed into a
polymer substrate using an embossing tool manufactured by companies
such as Jenoptik Microtechnic GmBH in Germany. In this case, a mold
or negative replica of the system is first etched into silicon to
form an embossing tool. The tool is then embossed into the polymer
substrate at an appropriate softening temperature and then
retracted. The tool can be reused to create more replicas reducing
the cost per piece. Access holes can be drilled into the embossed
polymer substrate. Another thin sheet of polymer can be chemically
bonded to cover the channels.
[0091] FIGS. 3c and 3d show a cross-sectional side view and a top
view, respectively, of a pump 320 that is suitable for use in
microfluidic system 104 (FIG. 1). Pump 320 includes diaphragm 338
that causes alternating volumetric changes in a pump chamber 340
when deflected. When pump chamber 340 contains liquids or gases,
they are transferred by the pumping action into another chamber or
reservoir (not shown) via channels 342, 344 in substrate 346. Check
valves 348, 350 are located in channels 342, 344, respectively, to
control the flow of fluid into and out of chamber 340. The
diaphragm 338 is actuated electro-magnetically with magnetic member
352 being controlled by magnetic core 354 and alternating current
in solenoid 356.
[0092] Techniques known in the art, such as silicon etching,
plastic injection molding, and hot embossing can also be used to
fabricate microfluidic system 104. A combination of fabrication
methods well-known in the art can be used to fabricate flow
channels 342, 344, pump chamber 340, and check valves 348, 350 in
substrate 346.
[0093] In one embodiment, the top side of microfluidic system 104
includes channels 342, 344, and pump chamber 340. The top and
bottom sides can include access holes 357, 367 for loading reagents
and other substances into chamber 340, as required. The sample(s)
and reagents can be introduced using a syringe and then access
holes 357, 367 are sealed by chemically bonding layers 360, 362 to
the top and/or bottom sides, respective.
[0094] Microfluidic system 104 can also be fabricated out of one or
more layers of molded or embossed polymers. In one embodiment,
channels, reservoirs, pump chambers, and check valves are embossed
in substrate 346. A flexible layer is chemically bonded to the top
of substrate 346, to form diaphragm 338 and seal the channels,
reservoirs, and access holes on the top side. Magnetic members 352
for pumps 320 are positioned on top of the second layer. A top
protective layer 360 and/or a bottom protective layer 362 can be
included to seal and protect the top and bottom of substrate 346,
as shown in FIG. 3c. The top protective layer 360 is flexible to
allow movement of diaphragm 352 during actuation.
[0095] Diaphragm 338 is attached to the top of substrate 346 and is
made out of a thin sheet of flexible material such as plastic,
glass, silicon, elastomer, or any other suitable, flexible
material. The flexibility or stiffness required of diaphragm 338
depends on the desired deflection of the diaphragm. Typically the
stiffness is selected to achieve a total upward and downward
deflection of approximately five to fifteen microns. Any suitable
attachment mechanism, such as chemical bonding, can be used to
attach diaphragm 338 to substrate 346. The bonding technique
utilized should be capable of maintaining the seal while the pump
320 is operating.
[0096] Magnetic member 352 is made out of magnetic material which
is attracted and repelled by a magnetic force from magnetic core
354. Magnetic member 352 can be adhesively bonded to diaphragm 338,
or electroplated onto the diaphragm 338 during manufacturing.
Substrate 346 can be made of plastic, silicon, or other suitable
material that is capable of substantially retaining the shape of
pump chamber 340 during operation.
[0097] An electrically conductive wire is coiled around magnetic
core 354 to form solenoid 356. When an electric current passes
through solenoid 356, a magnetic field is created in magnetic core
354. The polarity of the current can be alternated to change the
direction of force of the magnetic field, thus alternately
repelling and attracting magnetic member 352. The repelling and
attracting forces cause diaphragm 338 to move, changing the volume
of chamber 340. An increase in volume draws fluid or gas into
chamber 340 via channel 342, and a decrease in volume forces the
fluid or gas into channel 344. Applying a periodic excitation
voltage to solenoid 356, such as provided by current source 364,
causes diaphragm 338 to oscillate, producing a pumping action. The
flow rate is thus directly controlled by the frequency of the
alternating current to solenoid 356.
[0098] Note that the current through solenoid 356 can have a
positive or negative sign that produces a magnetic field in
magnetic core 354. One end of the magnetic core 354 becomes
positively charged, and the other end becomes negatively charged.
When the sign of the current through solenoid 356 is reversed, the
charge at the ends of magnetic core 354 also reverse. When the
current is shut off, magnetic core 354 loses its magnetism.
Further, magnetic member 352 has a positively charged end, and a
negatively charged end. Magnetic member 352 is attracted to
magnetic core 354 when the ends closest to each other are
oppositely charged. Similarly, magnetic member 352 is repelled by
magnetic core 354 when the ends closest to each other have the same
charge. The strength of the attraction or repulsion depends on the
number of windings in solenoid 356, and the strength of the
electric current.
[0099] Check valve 348 controls the inflow of fluid or gas into
chamber 340, and check valve 350 controls flow out of chamber 340.
Check valve 348 allows fluid to flow into chamber 340 when the
volume of chamber 340 is increased, and prevents backflow of the
fluid or gas when the volume of chamber 340 is decreased. Flow
through channel 344 is controlled by check valve 350, which allows
flow into channel 344 when the volume of chamber 340 is decreased,
and prevents backflow from channel 344 when the volume of chamber
340 is increased.
[0100] Pump 337 is well-suited for use with a variety of devices,
in addition to microfluidic system 104, because the components
associated with actuating pump 337, namely, magnetic member 352,
magnetic core 354, and coil 356, can be fabricated to a wide range
of dimensions, including micro-scale dimensions. Flow rates can be
adjusted by varying the frequency and amplitude of the alternating
current through solenoid 356. Additionally, an electronic,
microprocessor-based control system 366, as known in the art and
shown in FIG. 3e, can be implemented to receive sensor input from
flow sensors 368 that measure the flow into and/or out of pump 337.
For example, a Digital Signal Processor such as model number
ADSP-2181 by Analog Devices, Inc. of Norwood, Mass., can be used as
the controller. Logic associated with control system 366 compares
the actual flow rate to the desired flow rate, and provides a drive
signal to current source 364 to adjust the frequency and amplitude
of the current source 364 accordingly to achieve the desired flow
rate from pump 337.
[0101] Referring again to FIGS. 3c and 3d, magnetic member 352 is
located on diaphragm 338. Magnetic core 354 is positioned close
enough for its magnetic field to actuate diaphragm 338. Magnetic
core 354 with solenoid 356 can be positioned above magnetic member
352 or below chamber 340, depending on the strength of the magnetic
field developed by the magnetic core. Instead of a single
electromagnet, two magnets placed on opposite sides of the magnetic
member 352 can also be used in a push-pull configuration to
maximize deflection. Further, magnetic core 354, solenoid 356, and
current source 364 can be built into a structure surrounding
substrate 346, diaphragm 338, and magnetic member 352.
[0102] Other types of devices for creating magnetic fields for
actuating the magnetic member 352 can also be utilized with the
present invention, instead of, or in addition to an electromagnet.
For example, permanent magnets with opposing charges can be mounted
on a structure that moves toward and away from the magnetic member
352 at a periodic, variable rate, thereby actuating diaphragm 338.
The magnet having a like charge to the magnetic member 352 would be
used to repel the magnetic member 352, while the magnet having the
opposite charge would be used to attract the magnetic member 352.
Other alternatives known in the art for attracting and repelling a
magnetic member 352 can also be utilized.
[0103] Various types of check valves are suitable for use with the
pump 320 to control the flow of fluid, gas, or other substance in
the desired direction. In one embodiment, as shown in FIG. 3d,
check valves 348 and 350 are passive flaps etched or molded in the
substrate 346. As shown in FIG. 3d, check valves 348, 350 are a
substantially straight flap having a length that is longer than the
width of channels 342, 344. The flap is angularly positioned across
the width of the channel, with the end that is closer to the start
of the flow being anchored to a sidewall of the channels 342, 344,
while the other end of the flap is free-floating. This type of
construction can be achieved by cutting or etching around the
substrate material to leave it attached to one sidewall, while
cutting or etching through the material to free it from the other
sidewall. If an injection molding process is used, the mold is
continuous between the sidewall and the flap to leave it attached
to the sidewall, while a space is left between the other end of the
flap and the sidewall.
[0104] The force of a substance, such as a fluid or gas, being
pumped through channels 342, 344 tries to align the flap with the
direction of the flow. The substance passes through channel 342 as
the free-floating end of the flap moves away from the sidewall with
the direction of the flow caused by the vacuum that is created when
diaphragm 338 is raised. The vacuum created by upward movement of
diaphragm 338 also forces the free end of check valve 350 into the
sidewall of channel 344, thereby preventing backflow from channel
344. The reverse happens when the diaphragm moves downward and the
fluid is propelled in one direction.
[0105] It is anticipated that some embodiments of biosensor device
102 would include one or more bi-directional valves. Further, the
operation of both unidirectional and bi-directional valves could be
controlled by the force of the flow created by actuating diaphragm
338, or electronically using logic in valve controller 164 (FIG.
1a) to open and close valves 348, 350, in FIG. 3d.
[0106] It is important to note that one or more channels, such as
channel 342 in FIG. 3d, can feed into pump chamber 340. Likewise,
one or more channels, such as channel 344, can be used to transport
a substance out of pump chamber 340.
[0107] FIG. 3f shows a diagram of a typical piezoelectric micropump
380 found in the art that is suitable for use with the present
invention in addition to, or instead of, pump 320 (FIG. 3e). Pump
380 includes a pump chamber 382 which is capped by heat-resistant
glass layer 388 which also forms the diaphragm. Piezoelectric
element 390 is bonded to diaphragm 388. Applying a voltage from
voltage source 386 to the piezoelectric element 390 induces either
an upward or downward deflection depending upon the polarity of the
applied voltage. This changes the volume of the pump chamber 382,
causing it to draw fluid through an inlet valve, and to pump fluid
through an outlet valve, on opposite strokes of the cycle. Applying
a periodic excitation voltage causes diaphragm 388 to oscillate,
producing a pumping action. The flow rate is thus directly
controlled by the frequency of the electrical drive signal to the
piezoelectric element 390.
[0108] Substrate 392 can be fabricated from polymer or silicon
material. The glass layer 384 is bonded onto substrate 392 using a
suitable bonding method, such as anodic or epoxy bonding, to
prevent leakage. Polyimides and thermal laminants can also be used
for bonding and have the advantage of a lower bonding
temperature.
[0109] One way to mix very small amounts of two or more substances
in microfluidic system 104 is to feed the flow streams into one
channel as they are directed to a reservoir or pump chamber. An
alternative way includes injecting one substance into another using
micro-nozzles. Referring now to FIG. 3g, one embodiment of mixer
394 with micro-nozzles is shown that is suitable for use with the
present invention microfluidic system 104. Mixer 394 includes a
mixing chamber 396 with nozzles 398 on one side. During operation,
the mixing chamber 396 is filled with one or more substances, and
another substance is injected through the nozzles 398, thereby
generating a plurality of micro-plumes. The plumes effectively mix
the substances without requiring any additional processing. Mixing
time depends on injection flow rate, size of nozzles, distance
between each nozzle and size of the mixing chamber. Nozzles with
orifices as small as one (1) micrometer can be provided using known
fabrication processes.
[0110] Information from biosensor device 102 can be accessed by
authorized users when biosensor device 102 is connected to an
information network. One embodiment of components and connections
between components in information network 410 that can be used with
the present invention is shown in FIG. 4. Users access information
and interface with information network 410 through workstations
412. Workstations 412 execute application programs for presenting
information from, and entering data and selections as input to
interface with information network 410. Workstations 412 also
execute one or more application programs to establish a connection
with server 416 through network 420. Various communication links
can be utilized, such as a dial-up wired connection with a modem, a
direct link such as a T1, ISDN, or cable line, a wireless
connection through a cellular or satellite network, or a local data
transport system such as Ethernet or token ring over a local area
network. Accordingly, network 420 includes networking equipment
that is suitable to support the communication link being
utilized.
[0111] Those skilled in the art will appreciate that workstations
412 can be one of a variety of stationary and/or portable devices
that are capable of receiving input from a user and transmitting
data to the user. The devices can include visual display, audio
output, tactile input capability, and/or audio input/output
capability. Such devices can include, for example, biosensor system
100, desktop, notebook, laptop, and palmtop devices, television
set-top boxes and interactive or web-enabled televisions,
telephones, and other stationary or portable devices that include
information processing, storage, and networking components.
Additionally, each workstation 412 can be one of many workstations
connected to information network 410 as well as to other types of
networks such as a local area network (LAN), a wide area network
(WAN), or other information network.
[0112] Server 416 is implemented on one or more computer systems,
as are known in the art and commercially available. Such computer
systems can provide load balancing, task management, and backup
capacity in the event of failure of one or more computer systems in
server 416, to improve the availability of server 416. Server 416
can also be implemented on a distributed network of storage and
processor units, as known in the art, wherein the modules and
databases associated with the present invention reside on
workstations 412, thereby eliminating the need for server 416.
[0113] Server 416 includes database 422 and system processes 424.
Database 422 can reside within server 416, or it can reside on
another server system that is accessible to server 416. Database
422 contains information regarding users as well as results from
tests performed using biosensor device 102. Consequently, to
protect the confidentiality of such information, a security system
can be implemented that prevents unauthorized users from gaining
access to database 422. Users can be authorized to transmit and/or
receive information from database 422. User interface 114 (FIG. 1)
can allow the user to download and/or retrieve results from one or
more tests to database 422.
[0114] System processes 424 include program instructions for
performing analysis of data from biosensor device 102 and other
information provided by the user. The type of analysis performed is
based on the type of data being analyzed, and the type of
information to be provided to the user.
[0115] One application of biosensor system 100 is generating and
sharing information for medical diagnosis. A user can introduce a
sample to be analyzed, such as a drop of blood or other bodily
fluid, into microfluidic system 104. As discussed above, a variety
of different configurations can be implemented on microfluidic
system 104, depending on the specific test to be performed.
Accordingly, microfluidic system 104 includes the components, and
the type and amount of reagents required to perform one or more
assays on the sample.
[0116] Biosensor system 100 can screen for known pathogens for
infectious diseases and/or markers for genetic disorders. After the
sample is analyzed, the presence of a pathogen or a disease marker
(gene/protein) above a specific level can be indicated. Data from
each assay can be transmitted to server 416 directly from biosensor
system 100 or via workstation 412. The data is stored in server 416
using a personal, secured account that is generated for each user.
A subscriber, such as a physician and/or other authorized
individual, can be granted remote access to the user's account via
information network 420.
[0117] Advantageously, the electromagnetic pumps 100 do not require
electrical interconnects to operate.
[0118] Another advantage is that microfluidic system 400 may be
used to perform a variety of microfluidic and bio-analytical
functions, and can have varying levels of complexity depending on
the number of components included, and the functions to be
performed.
[0119] The foregoing detailed description has set forth various
embodiments of the present invention via the use of block diagrams,
flowcharts, and examples. It will be understood by those within the
art that each block diagram component, flowchart step, and
operations and/or components illustrated by the use of examples can
be implemented, individually and/or collectively, by a wide range
of hardware, software, firmware, or any combination thereof.
[0120] The above description is intended to be illustrative of the
invention and should not be taken to be limiting. Other embodiments
within the scope of the present invention are possible. Those
skilled in the art will readily implement the steps necessary to
provide the structures and the methods disclosed herein, and will
understand that the process parameters and sequence of steps are
given by way of example only and can be varied to achieve the
desired structure as well as modifications that are within the
scope of the invention. Variations and modifications of the
embodiments disclosed herein can be made based on the description
set forth herein, without departing from the spirit and scope of
the invention as set forth in the following claims.
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