U.S. patent number 5,194,133 [Application Number 07/695,429] was granted by the patent office on 1993-03-16 for sensor devices.
This patent grant is currently assigned to The General Electric Company, p.l.c.. Invention is credited to Michael G. Clark, Rosemary A. Lee, Christopher R. Lowe, Philip Maynard, Rajinder S. Sethi, Donald J. Weir.
United States Patent |
5,194,133 |
Clark , et al. |
March 16, 1993 |
Sensor devices
Abstract
A sensor device for the analysis of a sample fluid comprises a
substrate in a surface of which an elongate channel is
micromachined. The channel contains a material, such as a starch,
agarose, alginate, carrageenin or polyacrylic polymer gel, with a
biological material for causing separation of the sample fluid as
the fluid passes along the channel. The biological material may
comprise, for example, a binding protein, an antibody, a lectin, an
enzyme, a sequence of enzymes or a lipid. Pairs of sensing
electrodes are spaced apart along the walls of the channel. The
device may be used, for example, for testing blood samples.
Inventors: |
Clark; Michael G.
(Buckinghamshire, GB2), Lee; Rosemary A. (Middlesex,
GB2), Lowe; Christopher R. (Essex, GB2),
Maynard; Philip (Cambridgeshire, GB2), Sethi;
Rajinder S. (Northampton, GB2), Weir; Donald J.
(London, GB2) |
Assignee: |
The General Electric Company,
p.l.c. (GB2)
|
Family
ID: |
10675489 |
Appl.
No.: |
07/695,429 |
Filed: |
May 3, 1991 |
Foreign Application Priority Data
Current U.S.
Class: |
204/608;
204/403.01; 204/406; 204/412; 204/610; 422/527; 422/82.01; 436/525;
436/527; 436/806; 73/61.52 |
Current CPC
Class: |
G01N
30/64 (20130101); G01N 30/78 (20130101); G01N
27/27 (20130101); G01N 30/466 (20130101); G01N
30/6095 (20130101); G01N 2030/645 (20130101); Y10S
436/806 (20130101) |
Current International
Class: |
G01N
27/403 (20060101); G01N 30/78 (20060101); G01N
30/00 (20060101); G01N 30/64 (20060101); G01N
30/60 (20060101); G01N 30/46 (20060101); G01N
027/26 (); G01N 027/30 (); G01N 027/447 (); B01D
057/02 () |
Field of
Search: |
;204/403,412,411,409,406,299R,182.8,182.9 |
References Cited
[Referenced By]
U.S. Patent Documents
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4409088 |
November 1983 |
Kanno et al. |
4786394 |
November 1988 |
Enzer et al. |
4831442 |
October 1989 |
Yamaguchi et al. |
4891120 |
January 1990 |
Setti et al. |
|
Foreign Patent Documents
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0078590 |
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May 1983 |
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EP |
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0126426 |
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Nov 1984 |
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EP |
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0299778 |
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Jan 1989 |
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EP |
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0311377 |
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Apr 1989 |
|
EP |
|
59-178353 |
|
Oct 1980 |
|
JP |
|
2191110 |
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Dec 1987 |
|
GB |
|
Other References
Chemical Abstract CA 108(24):215569b; Vanini, G. M. et al., "Neat
and admixed mesomorphic polysiloxane otationary phases for
open-tubular column gas chromatography" Anal. Chem. 60(11),
1119-24. .
Ma, T. S. & Hassan, S. S. M. "Organic Analysis Using
Ion-Selective Electrodes, vol. 1 Methods" pp. 109-113. .
Chemical Abstract CA115(4):40799; Laeubli, Markus W. "Simultaneous
determination of alkali and alkaline earth metal ions with
isocratic ion chromatography using the Super-Sep cation column
(according to Schomburg)", Recent Dev. Exch. 2 [Proc. Int. Conf.
Ion Exch. Process], 2nd, 31-9..
|
Primary Examiner: Niebling; John
Assistant Examiner: Starsiek, Jr.; John S.
Attorney, Agent or Firm: Kirschstein, Ottinger, Israel &
Schiffmiller
Claims
We claim:
1. A sensor device for analysis of a sample fluid, the device
comprising: a substrate having a surface; at least one elongate
channel micromachined in the surface of the substrate for carrying
said sample fluid, the channel having a length and opposed side
walls; separation means, including a material in the channel, for
causing separation of said sample fluid carried by the channel; a
plurality of sensing electrode pairs spaced apart along the length
of the channel, the electrodes of each pair being located opposite
each other across the channel, and each electrode having a portion
within the channel at one of said side walls; and means coupled to
the electrodes for processing signals dependent upon conditions
existing between the electrodes of each pair.
2. A device as claimed in claim 1, wherein the channel is packed
with a gel; and wherein the material comprises a biological
substance which is attached to the gel.
3. A device as claimed in claim 2, wherein the biological substance
comprises a substance which interacts selectively and reversibly
with the sample fluid.
4. A device as claimed in claim 3, wherein the biological substance
is selected from the group consisting of a binding protein, an
antibody, a lectin, an enzyme, a sequence of enzymes, and a
lipid.
5. A device as claimed in claim 2, wherein the gel is selected from
the group consisting of starch, agarose, alginate, carrageenin, a
polyacrylic polymer and an inorganic gel.
6. A device as claimed in claim 1, wherein the walls of the channel
are coated with a biological substance.
7. A device as claimed in claim 1, wherein the channel contains a
body of a biological substance.
8. A device as claimed in claim 1, wherein the channel communicates
with a well formed in the substrate and containing a biological
substance.
9. A device as claimed in claim 1, wherein the material comprises a
liquid crystal material.
10. A device as claimed in claim 9, wherein the liquid crystal
material comprises a mesomorphic polysiloxane polymer.
11. A device as claimed in claim 1, wherein the material comprises
polystyrene-divinylbenzene.
12. A device as claimed in claim 1, wherein the material comprises
a silica-based ion exchange phase.
13. A device as claimed in claim 12, wherein the silica-based ion
exchange phase is provided by depositing a layer of the co-polymer
polybutadiene-malic acid on the walls of the channel and
cross-linking said layer by a peroxide-initiated radical chain
reaction.
14. A device as claimed in claim 1, wherein the material comprises
a silica-bonded macrocycle.
15. A device as claimed in claim 14, wherein the macrocycle
comprises a crown ether.
16. A device as claimed in claim 1, wherein the material comprises
a carboxylic polyether antibiotic.
17. A device as claimed in claim 16, wherein the antibiotic is
selected from the group consisting of ionomycin, lasalocid,
monensin, nigericin and salinomycin, covalently bonded to
silica.
18. A device as claimed in claim 1, wherein the material comprises
an electrosynthesized chromatographic stationary phase.
19. A device as claimed in claim 1, wherein the channel is formed
by one of a chemical and physical etching process.
20. A device as claimed in claim 1, wherein the resolution of
components of the sample fluid is effected by one of capillary
chromatography, electrophoresis, and iso-electric focussing.
21. A device as claimed in claim 1, wherein the substrate is formed
from one of silicon, glass and ceramic.
22. A device as claimed in claim 1, wherein contact pins are
connected to respective ones of the electrodes, the contact pins
being configured for insertion into a dual-in-line integrated
circuit holder.
23. A sensor device for analysis of a sample fluid, the device
comprising: a substrate having a surface; at least one elongate
channel micromachined in the surface of the substrate for carrying
said sample fluid, the channel having a length and opposed side
walls; separation means, including a material in the channel, for
causing separation of said sample fluid carried by the channel; a
plurality of sensing electrode pairs equally spaced apart along the
length of the channel, the electrodes of each pair being located
opposite each other on the opposed side walls of the channel; and
means coupled to the electrodes for processing signals dependent
upon conditions existing between the electrodes of each pair.
24. A sensor device for analysis of a sample fluid, the device
comprising: a substrate having a surface; at least one elongate
channel micromachined in the surface of the substrate for carrying
said sample fluid the channel having a length, opposite ends and
opposed side walls; separation means, including a material in the
channel, for causing separation of said sample fluid carried by the
channel; a plurality of sensing electrode pairs spaced apart along
the length of the channel, the electrodes of each pair being
located opposite each other on the opposed side walls of the
channel, the spacing between adjacent electrode pairs increasing
from one of said ends of the channel to the other of said ends; and
means coupled to the electrodes for processing signals dependent
upon conditions existing between the electrodes of each pair.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to sensor devices, and particularly, but not
exclusively, to sensors for use in clinical analysis.
2. Description of Related Art
There is an increasing demand for analytical information in sectors
including health care and veterinary medicine, and in the food,
pharmaceutical, bioprocessing, agrochemical and petrochemical
industries. This information is at present mainly provided by
sophisticated centralised analytical laboratories. Such
laboratories are both capital and labour intensive, and there is
evidence that they are unlikely to meet the needs of the future.
For example, in human health care, speed in both the detection and
monitoring of key metabolities is essential for the correct
diagnosis and subsequent treatment of diseases, and this requires
the provision of local, fast analysis.
The need to perform analysis in a non-laboratory environment
requires new diagnostic techniques in order to provide real-time
information on the levels of key substances such as gases, ions,
metabolites, drug, proteins and hormones. Unequivocal diagnosis
will usually depend on the simultaneous determination of several
key metabolites, as would be required, for example, for the
diagnosis and management of diabetes, kidney, liver and thyroid
dysfunction, bone disorders and cardiovascular disease.
Furthermore, such determination could also prove valuable in blood
and tissue typing and in screening for pregnancy complications,
fertility, drug abuse, neonatal disorder, infectious diseases,
rheumatic disorders and drug overdoses.
A sensor device for such purposes should preferably be small and
easily portable and should not require complex prior preparation of
the sample, such as blood, to be tested.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved
sensor device.
According to the invention there is provided a sensor device for
analysis of a sample fluid, the device comprising a substrate; at
least one elongate channel micromachined in a surface of the
substrate and containing a material to cause separation of said
sample fluid as the fluid passes along the channel; and a plurality
of sensing electrode pairs spaced apart along the channel, the
electrodes of each pair being located opposite each other at
opposed side walls of the channel.
If necessary, a cover will be provided over the or each channel for
retaining the fluid in the channel.
Preferably the material to cause separation comprises a gel to
which is attached a biological material and with which the or each
channel is packed. The gel may be, for example, a carbohydrate e.g.
starch, agarose, alginate, carrageenin, a polyacrylic polymer, or
an inorganic gel. The channel walls may be coated with a biological
substance, such as an enzyme. The material to cause separation is
chosen to have different affinity for different components of the
sample fluid, and may, for example, be a liquid crystal polymer or
an ionisable polymer, according to the nature of the sample fluid.
Alternatively, the material to cause separation may be a binding
protein, antibody, lectin, enzyme or sequence of enzymes, lipid or
any other chemical which interacts selectively and reversibly with
the substance which is to be separated.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments of the invention will now be described, by way of
example, with reference to the accompanying drawings, in which
FIG. 1 is a schematic plan view of a first form of sensor device in
accordance with the invention;
FIG. 2 is a schematic pictorial view of the device of FIG. 1;
FIG. 3 is a schematic plan view of a second form of sensor device
in accordance with the invention;
FIG. 4 is a schematic plan view of a third form of sensor device in
accordance with the invention;
FIG. 5 is a schematic plan view of a fourth form of sensor device
in accordance with the invention; and
FIG. 6 is a schematic block diagram of circuitry for processing the
outputs of the sensor devices.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1 of the drawings, a sensor device 1 comprises a
substrate 2 in which an elongate groove 3 is formed by a
micromachining process. The substrate may be formed of glass,
ceramic or silicon, on which is deposited or grown a layer of
dielectric material, such as silicon dioxide. The micromachining
process may comprise chemical or physical etching of the
substrate.
The width of the groove 3 may be in a range of, say, 10-500 .mu.m,
and is preferably about 100 .mu.m. Its depth may be 50 .mu.m or
more and its length will preferably be greater than 1 mm.
Electrode pairs 4 are deposited on the substrate so that part of
each electrode extends down the side wall of the groove 3, the
electrodes of each pair lying on opposite sides of the groove. The
electrode pairs are equally spaced along the length of the groove.
The electrodes are preferably formed of a corrosion-resistant
material, such as gold, platinum or iridium, and are deposited by
any suitable deposition process, such as sputtering. The walls of
the groove may be previously recessed at the electrode positions,
so that the electrodes lie flush with the groove walls in order not
to impede the flow of a liquid sample through the groove.
Conductors 5 are deposited across the substrate surface to connect
the electrodes to respective contact pins 6. The contact pins may
turn downwards as shown, so that the device may be plugged into a
standard dual-in-line integrated circuit holder. Alternatively, the
electrodes may be connected to contact pads on the surface of the
substrate.
FIG. 3 is a schematic plan view of an alternative form of sensor
device 7. A groove 8 is formed in a substrate 9, and electrode
pairs 10 are provided at the groove walls as before. However, in
this case the electrodes are not equidistantly spaced along the
length of the groove. In order to achieve a maximum number of
measurement positions and a configuration more in keeping with the
expected progress of the separation function of the groove,
successive electrode pairs are spaced apart at distances of 1 unit,
2 units, 3 units, 4 units, and so on. If desired, the contact pins
or pads could be equally spaced along the substrate to facilitate
their connection to the monitoring circuitry.
Wells 11 and 12 are provided at opposite ends of the groove 8 to
facilitate the introduction of the sample fluid into the groove and
its collection after passing along the groove. Electrodes are
preferably provided in the wells for electrophoresis purposes.
FIG. 4 shows an alternative configuration of sensor device 13 in
which a groove 14 is formed in serpentine fashion in a substrate
15. This appreciably increases the length of the groove. The
electrode pairs may be equally spaced or unequally spaced along the
length of the groove. Wells are provided at the ends of the
groove.
Referring to FIG. 5, in another alternative configuration a sensor
device 16 comprises a substrate 17 in which three parallel grooves
18-20 are formed and associated electrode pairs are provided. A
well 21 formed in the substrate for receiving a sample fluid is
common to the three grooves 18-20. The well 21 is connected by
grooves 22, 23 and 24, respectively, to wells 25, 26 and 27 with
which the ends of the grooves 18, 19 and 20, respectively,
communicate. The wells 25-27 are provided to receive an enzyme
material, as will be explained later. Wells 28, 29 and 30 are
provided near the other end of the substrate 17 to receive sample
fluid after it has flowed through the grooves 18, 19 and 20,
respectively. This arrangement allows two sample fluids and a
reference fluid to be derived from the fluid fed into the well 21
and to flow through the device simultaneously. Alternatively, the
grooves may be used for simultaneous measurement of a number of
different indicating chemicals. The device may alternatively have
any other required number of parallel grooves. For example, six
grooves might be used for measurement, respectively, of levels of
potassium, sodium, creatimine, urea, C1.sup.- and HCO.sub.3 in a
blood sample, as would be required for the diagnosis of kidney
disease.
In each of the above-described embodiments the grooves are filled
with a substance which causes them to act as chromatographic
separating columns. The grooves contain a biological material, such
as a binding protein, antibody, lectin, enzyme or sequence of
enzymes, lipid or any other chemical which interacts selectively
and reversibly with the substance which is to be separated. The
grooves may be lined with the material, or the grooves may be
packed with a gel to which the material is attached. The gel may
be, for example, a carbohydrate e.g. starch, agarose, alginate,
carrageenin, a polyacrylic polymer, or an inorganic gel.
Alternatively, the electrodes may be amperometric enzyme electrodes
deposited by micro-fabrication techniques.
If the sample fluid is a liquid or, more particularly, a gas
containing different anisometric molecules, an appropriate
chromatographic substance is a liquid crystal polymer in which the
liquid crystal forming molecules are attached as side-chains to the
polymer by flexible spacers. The sensor is then preferably operated
in the temperature range within which the polymer is in a liquid
crystal phase, although separation is improved by use of a liquid
crystal polymer even in its isotropic phase. One example of a class
of liquid crystal polymers suitable for use in the present
invention is the mesomorphic polysiloxane (MEPSIL) polymers
described by G. M. Janini, R. J. Lamb, J. H. Purnell and O. S.
Tyagi in their article "Physicochemical Studies and Analytical
Applications of Mesomorphic Polysiloxane (MEPSIL) Solvents by
Gas-Liquid Chromatography" published as Chapter 14 in "Side Chain
Liquid Crystal Polymers" (edited by C. B. McArdle; Blackie, 1989).
Separations using liquid crystalline chromatographic substances
show particularly good resolution because the interactions between
molecules in the sample and the liquid crystal side chains are very
dependent on geometrical shape. Liquid crystals are therefore
particularly suited to separating geometrical isomers or other very
similar pairs of molecules.
The most appropriate method of ionic species resolution is
exploitation of ion chromatography. This technique is a special
version of high performance ion exchange chromatography by which
ionic and ionizable solutes can be separated by differences in the
electrostatic interaction with an ionizable stationary phase. The
detection of the ionic species separated chromatographically is
achieved using the pairs of electrodes configured as a conductivity
device.
Any of a number of types of stationary phase may be inserted into
the microgrooves in order to make them effective in resolving
isocratically a mixture of mono- and divalent cations and anions.
Such phases include
(i) Polystyrene-divinylbenzene (PS-DVB). Chemical modification of
the polymer allows preparation of anion or cation exchange
stationary phases with excellent pH stability in the range
0-14.
(ii) Silica-based ion exchange phases. Silanised silica or
polymer-coated silica are effective phase media for ion
chromatography. For example, a layer of the co-polymer
polybutadiene-maleic acid (PBDMA) deposited on the walls of the
groove or grooves in various thicknesses and then cross-linked by a
peroxide initiated radical chain reaction via the in-chain double
bonds yields an insoluble film capable of serving as a stationary
phase for ion chromatography. ##STR1##
(iii) Silica-bonded macrocycles. The attachment of macrocycles such
as the crown ethers to silica makes possible the design of systems
capable of the selective and quantative removal of cations from
aqueous solutions. Immobilisation of 18-crown-6 to the silica walls
of the groove at an appropriate ligand density should permit
isocratic separation of the complementary cations. Isocratic
separation is a type of chromatography in which all solutes are
separated by their affinity for a solid phase with a fixed running
phase.
(iv) Natural carboxylic polyether antibiotics. The carboxylic
polyethers are a class of antibiotics produced by various
Streptomyces species containing heterocyclic rings and a variety of
functional oxygen atoms of the carbonyl, carboxyl, ether, hydroxyl
and ketone types. Such compounds are capable of forming selective
complexes with alkali-metal and alkaline earth metal cations.
Hence, the carboxyl ethers ionomycin, lasalocid, monensin,
nigericin and salinomycin may be covalently bonded to silica and
used for the resolution of complementary ions.
(v) Electrosynthesised chromatographic stationary phases.
Electrochemical synthesis of ion chromatography stationary phases
has a number of distinct advantages over the above procedures;
thus, it permits a rapid and easy column preparation, easy
modification of the stationary phase, production of a reproducible
physical and chemically stable polymer and accurate control of
stationary phase thickness and composition. Polypyrrole,
incorporating various polymeric counter-anions such as CM-dextran,
dextran-sulphate heparin, gelatin or alginate may prove
particularly effective since it could be deposited in a controlled
fashion between the pairs of electrodes. Similarly,
polypyrrole-immobilised polyether antibiotics or macrocycles could
prove an effective alternative.
The two principal metabolites required for a kidney function test
device as mentioned above are urea and creatinine. Both metabolites
will be hydrolised to NH.sub.4 + using their respective hydrolases,
urease and creatininase. ##STR2## whence the liberated
NH.sub.4.sup.+ will be estimated by ion chromatography on
PBDMA-coated silica or one of the alternatives listed in (i-v)
above. Enzymes will be chemically cross-linked in the sample wells
of FIGS. 3 and 4, in the enzyme wells 25-27 of FIG. 5 or between
the pairs of electrodes via entrapment in electrochemically
deposited polypyrrole. Alternatively, a small "slug" of
electrochemically deposited enzyme could be deposited midway down
the length of the groove such that the first half of the groove
monitors the background conductance whilst the urea level is
monitored by the increased steady state conductance level as the
sample continuously passes through the enzyme "slug".
In operation of the above-described devices, a liquid, such as
blood, which is to be analysed is fed into one end of the groove or
grooves and is separated into its components by the substances
contained in the grooves. The components are then analysed as they
pass the electrodes on the groove wall.
The microfabrication techniques may alternatively be used to
fabricate microseparation structures based on capillary
chromatography, electrophoresis or iso-electric focussing.
Miniature fluid handling and metering devices, pumps and valves may
also be provided on the substrate by similar techniques. The
devices may also include a micromachined structure to feed a
filtered predetermined amount of sample fluid into the groove or
grooves.
FIG. 6 of the drawings is a schematic block diagram of circuitry
for processing the outputs from the sensor electrodes. The sensors
have a multiplicity of electrodes, for example sixteen on each side
of the groove, and it is necessary to read the impedance between
all the electrodes on one side of a groove and all the electrodes
on the other side in less than 10 seconds. The processing system
must therefore be capable of switching rapidly between electrodes,
without causing any electrochemical effects.
This rapid switching is accomplished by using a microcomputer 30 to
control a set of analogue switches. The signal applied to a
selected transmitting electrode on one side of the groove is a
reactangular dc pulse, 800 mV high and 120 .mu.s wide. The signal
received by the selected receiving electrode on the other side of
the groove is an attenuated version of the applied pulse, and the
degree of attenuation will be determined by the conductivity of the
media between the selected electrodes. The media conductivity has
many components, and these are to be studied, but other variables
involved in conductivity measurements such as surface area of the
electrodes and distance between them remains constant. The received
signal differs in appearance from the applied signal in that it
will be reduced in total height and the waveform will be rounded
off due to capacitive effects at the electrode surfaces. In order
to produce a detailed analysis of the received signal, sample and
hold circuitry is used such that data can be captured at time
intervals (20 .mu.s) from this signal.
The signals are fed to the selected transmitted electrodes via an
analogue multiplexer 31, and the signals from the receiving
electrodes are fed back to the microcomputer via an analogue
demultiplexer 32. The selection of the transmitting electrodes is
effected digitally by a 4-bit output latch 33 and the selection of
the receiving electrodes is effected by a 4-bit input latch 34. The
signal pulse train is fed to the multiplexer 31 via a buffer and
scaling circuit 35. The pulse train is obtained from the 0 bit of
an 8-bit computer control byte over a line 36. The signals from the
receiving electrodes are fed from the demultiplexer 32 to the
microcomputer via buffer, differential amplification and scaling
circuitry 37, sample and hold circuits 38-41 and an A/D converter
42. The signal from each receiving electrode is subtracted from the
transmitted signal in the circuitry 37. The difference signal is
amplified and is fed to the sample and hold circuits. The instant
of sampling is controlled by a 4-bit latch 43.
The other bits of the 8-bit control byte are operative as follows.
Bits 1, 2, 3 and 4, on lines 44-47, respectively, control the
selection processes at the latches 33, 34 and 43. Bits 5 and 6 on
lines 48 and 49 are fed to a 2:4 decoder 50 which determines which
of the latches 33, 34 or 43 is to be operative at any instant. Bit
7 on a line 51 controls a relay 52 which applies a voltage from an
external source to the electrodes in order to facilitate
electrophoresis.
In operation of the system, the computer sends out, via an
interface adaptor 53, the address of the selected transmitting
electrode, as four bits, using bits 1 and 4 inclusive. The data are
applied to the data latches 33, 34 and 43. Bits 5 and 6 carry the
address of the output latch 33, which is selected by the decoder
50. The four bits selecting the transmitting electrode are thus
transferred to the multiplexer 31.
The receiving electrode is then selected in the same manner, its
4-bit address being determined by bits 1-4, and is latched through
the input latch 34 by decoding bits 5 and 6 in the decoder 50.
When the transmitting and receiving electrode pair has been
selected, bit 0 goes high, and acts as the source of the signal to
be applied to the transmitting electrode. Bits 5 and 6 are set such
that they do not select any of the latches. The buffer and scaling
circuit 35, consisting of simple operational amplifiers, reduces a
5 volt output signal applied from bit 0 to 800 mV and this is fed
to the multiplexer 32 and thence to the selected electrode. The
signal is also applied to the differential amplifier circuitry 37.
The signal received by the selected receiving electrode passes
through the demultiplexer 32 and is fed to the buffer, differential
amplifier and scaling circuit 37 and then to the inputs of the four
sample and hold circuits 38-41. (Bit 0 is still high at this
point).
While the bit 0 is held high, one of the sample and hold circuits
38-41 is selected by setting the bits 1 to 4. The sample and hold
latch 43 is then selected by bits 5 and 6 to enable the latch, and
thereby store the output from the analogue circuitry. This is
repeated to capture the analogue data on the next sample and hold
circuit. The sample and hold circuits may be enabled at, for
example, 20 .mu.sec intervals.
When all four sample and hold circuits 38-41 have data stored in
them, the control byte is set to 0 (unless the relay 52 is enabled
by the bit 7) thereby removing the applied analogue signal. The
data from each sample and hold circuit is read into the four
channels of the A/D converter 42. The next transmitting electrode
can then be selected by repeating the steps described above.
As an example, let us assume that a signal is to be fed to the
third transmitting electrode in the sequence and that a signal is
to be received on the sixth receiving electrode. The codes to be
produced by the microcomputer will be as set out in Table 1
below.
TABLE 1 ______________________________________ Control Byte Bit
Number 7 6 5 4 3 2 1 0 ______________________________________ 0 0 0
0 0 1 1 0 Select third transmitter electrode 0 0 1 0 0 1 1 0 Send
to multiplexer 31 by enabling output latch 33 (address 1) 0 0 0 0 1
1 0 0 Select sixth receiving electrode 0 1 0 0 1 1 0 0 Send to
demultiplexer 32 by enabling input latch 34 (address 2) 0 0 0 0 0 0
0 1 Apply analogue signal to transmitter electrode 0 0 0 0 0 0 1 1
Select sample and hold circuit 38 0 1 1 0 0 0 1 1 Enable from
sample and hold latch 43 0 0 0 0 0 1 0 1 Select sample and hold
circuit 39 0 1 1 0 0 1 0 1 latch as above 0 0 0 0 0 1 1 1 Select
sample and hold circuit 40 0 1 1 0 0 1 1 1 latch as above 0 0 0 0 1
0 0 1 Select sample and hold circuit 41 0 1 1 0 1 0 0 1 latch as
above 0 0 0 0 0 0 0 0 All off 1 0 0 0 0 0 0 0 Relay 52 on
______________________________________
The circuitry described above has been designed to provide a
measurement system capable of monitoring the bulk impedance of any
media which may be found between the electrodes of a
micro-electrode array. Conventional methods of measuring impedance
in this type of environment require an alternating current source
of very low voltage to be applied across a pair of electrodes which
together with the separating media form one arm of a bridge
circuit. In order to achieve steady readings, the bridge circuit
automatically adjusts until balance is achieved. During this
adjustment period, energy is continually applied to the measuring
electrodes, inducing local heating due to the very small electrode
area, and possibly causing some electrochemical effects. Switching
electrodes in and out of a measurement system will cause local
effects, changing the impedance measurement itself and increasing
the length of time required by a bridge circuit to balance.
The measurement system described herein alleviates these problems
associated with the conventional methods.
It would be possible to form the sensor devices described above as
two identical micromachined substrates, which are then bonded
together, face to face, to form an enclosed device. Alternatively,
a cover plate might be bonded to any of the devices to cover the
grooves.
* * * * *