Active solid-state devices (e.g. – transistors – solid-state diode – Field effect device – Responsive to non-optical – non-electrical signal
Reexamination Certificate
1998-07-08
2001-07-03
Lee, Eddie (Department: 2815)
Active solid-state devices (e.g., transistors, solid-state diode
Field effect device
Responsive to non-optical, non-electrical signal
C257S253000, C257S414000, C257S467000, C257S469000, C257S470000, C438S049000
Reexamination Certificate
active
06255677
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an analysis device comprising an electronic chip equipped with a plurality of electrodes. Such a chip is used to constitute a miniaturized chemical or biological analysis cell. This is because each electrode of the chip can be coated individually with a compound or a material sensitive to a specific chemical or biological product.
An analysis device in accordance with the invention can be used, for example, as a glucose measurer, or as a device for blood analysis or for analysis of various chemical or biological products.
A particular application of the device of the invention in the field of molecular biology is that of antibody/antigen recognition. Similarly, the device can also be used in DNA chips.
PRIOR ART
An electronic chip for an analysis device as mentioned above may include several hundred electrodes each carrying a DNA probe. DNA probe means DNA molecules having a predetermined known sequence. The selective hybridization of DNA molecules in a medium to be analyzed with the probe molecules fixed on the electrodes makes it possible to know the composition of this medium. By way of example, it is possible to perform a genetic analysis on mutations responsible for a given type of cancer.
Of course, in other analysis applications, the probe molecules are replaced by any appropriate reagent sensitive to a given substance liable to be in the medium to be analyzed.
The accompanying
FIGS. 1
to
4
illustrate the structure and use of chips with electrodes for analyzing a medium.
FIG. 1
shows in section and schematically a biological sensor chip
10
as used for antibody/antigen recognition or as a DNA/DNA probe for a patient.
Chip
10
includes so-called analysis electrodes
12
a
and
12
b
and addressing electrodes
14
. Although the number of electrodes present on an analysis chip is generally high, of the order of ten to several hundred, chip
10
of
FIG. 1
is shown with only two analysis electrodes and a single addressing electrode, for obvious reasons of clarity. The analysis electrodes can be electrically addressed by corresponding addressing electrodes. However, when the number of analysis electrodes is very large, the chip may include a multiplexed addressing device making it possible to address all the analysis electrodes from a reduced number of addressing electrodes.
Addressing means making the electrical connection of one or more analysis electrodes with one or more so-called addressing electrodes generally arranged at the periphery of the chip. The addressing electrodes make it possible to apply or measure a voltage on the analysis electrodes, by means of suitable external apparatus.
Generally, analysis electrodes
12
a
and
12
b
are made of a metal such as, for example, gold or platinum. They are mutually isolated from one another on a wafer of substrate
16
. Electrical connections between analysis electrodes
12
a,
12
b
and the addressing electrodes are arranged in substrate
16
and are indicated very schematically with reference
18
.
A chip, such as depicted in
FIG. 1
, must be configured for a particular use and the analysis electrodes are to that end made functional by coating them with probe molecules or by covering their surfaces with a deposit of appropriate reagent.
The deposition of reactive products or the transplanting of probe molecules onto the electrodes is carried out, in general, by electrodeposition.
The reagents or probe molecules deposited on the electrodes allow, as indicated previously, a selective pairing with specific molecules of a substance to be analyzed. These molecules are designated “target molecules” in the remainder of the text.
FIG. 2
shows chip
10
immersed in a bath of electrolyte
20
. Bath of electrolyte means a bath suitable for depositing, by electrochemistry, a reagent on the electrodes, or a bath in which probe molecules which have to be fixed by electrodeposition on the electrodes are diluted.
The selective application of a bias voltage between selected analysis electrodes and a reference electrode makes it possible to fix thereon the reactive product or the probe molecules. The voltage is applied to the electrodes by means of an external generator
24
connected to addressing electrodes
14
.
The probe molecules are fixed on the analysis electrodes, for example, by means of conductive polymers of polypyrrole or polyaniline type which are carriers of probe molecules.
The chip may undergo several electrochemical deposition steps, being dipped in different baths. Thus, different electrodes of the chip can be covered with different reagents, or probe molecules, sensitive to different compounds of the substances to be analyzed.
In
FIG. 2
, it is considered that the two electrodes
12
a
and
12
b
are respectively (and successively) covered with different reagents, or probe molecules,
22
a,
22
b.
At the end of the coating of the electrodes with the reagents, of probe molecules, the chip is ready to be used in order to analyze a substance, designated analyte in the remainder of the description.
As shown in
FIG. 3
, chip
10
is disconnected from the generator and is immersed in a bath
30
containing the analyte.
This bath contains, for example, target molecules
32
which pair or react with the reagent or the probe molecules
22
a
previously deposited on the first electrode
12
a.
For reasons of clarity, target molecules
32
are depicted schematically and magnified.
Target molecules
32
do not however interact with the second electrode
12
b,
whose reactive coating, or probe molecules, are not compatible.
After having been extracted from the bath of analyte
30
, the chip is analyzed in order to determine the electrodes for which a reaction or a pairing has taken place.
In the example described in
FIG. 4
, chip
10
is analyzed by a method of detection by fluorescence. Such a method is particularly suitable when target molecules
32
are marked with a fluorescent marking product referred to as a fluorophore.
However, other analysis methods such as methods of electrical measurement by impedometry, of measurement by microbalance, optical measurements by change in refractive index, and methods of analysis by radioactive marking can also be envisaged.
As shown in
FIG. 4
, the whole of the chip
10
is subjected to light radiation
40
of a first wavelength and coming from a light source, not depicted.
The marked target molecules absorb the light radiation
40
and emit a light radiation
42
with a characteristic second wavelength, different from the first wavelength.
A detection device
46
, sensitive to the second wavelength, makes it possible to detect the light re-emitted from the electrodes carrying the target molecules marked with the fluorescent product. It is thus possible, by knowing the nature of the reagents or of the probe molecules previously deposited on each electrode, to determine the components of the analyte which are fixed thereto.
It emerges from the preceding description that a crucial step for the analysis is the so-called pairing or hybridization step during which the target molecules are fixed on the probe molecules or on the reagent.
In order to guarantee the reliability and reproducibility of the pairing or hybridization for electrodes having the same probe molecules, the chip and the analyte should in a certain number of cases be heated and maintained at a controlled constant temperature during the pairing or hybridization.
However, heating at a suitable temperature is possible only for chips on which substantially all the electrodes are coated with the same probe molecules. In fact, when different reagents or different probe molecules disposed on electrodes of one and the same chip require different hybridization or pairing temperatures, a reliable analysis is no longer possible.
A similar problem arises for the analysis chips used as DNA/DNA probes. On such a chip, a probe molecule of DNA, properly identified, is fixed on each electrode.
A plurality of distinct probe molecules can thus coat the electrodes of the chip. Each p
Caillat Patrice
Livache Thierry
Peltie Philippe
Burns Doane Swecker & Mathis
Commissariat A l'Energie Atomique
Lee Eddie
Warren Matthew E.
LandOfFree
Chip-based analysis device comprising electrodes with... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Chip-based analysis device comprising electrodes with..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Chip-based analysis device comprising electrodes with... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2562730