Patent Description:
The disclosure herein relates generally to the field of sensors used in the analysis of fluid properties. The disclosed sensor assembly is embodied in a sensor cartridge which is especially adapted for use in biomedical applications so as to assist in the analysis of multiple physical parameters and/or chemical constituents of small volume samples of bodily fluids such as whole blood.

In a variety of instances it is desirable to measure the constituents in a bodily fluid to include, for example, partial pressure of blood gasses in a whole blood sample, concentrations of electrolytes in the blood sample, and the hematocrit value of the blood sample. For example, measuring pCO<NUM>, pO<NUM>, pH, Na+, K+, Ca<NUM>+ and hematocrit value are primary clinical indications in assessing the condition of a medical patient. In addition, in an attempt to use as little of the patient's blood as possible in each analysis performed, the devices which are employed to analyze a blood sample are preferably relatively small. Performing blood analysis using a small blood sample is important, for example, when a relatively large number of samples must be taken in a relatively short amount of time or if the volume of blood is limited, as in neonates.

For example, patients in intensive care may require a sampling frequency of <NUM>-<NUM> per day for blood gas and clinical chemistry measurements, leading to a potentially large loss of blood during patient assessment. In addition, by reducing the size of the analyzer sufficiently to make the unit portable, analysis can be performed at the point of care. Also, reduced size typically means reduced turnaround time. Furthermore, in order to limit the number of tests which must be performed it is desirable to gather as much information as possible upon completion of each test. However, size limitations are imposed upon the sensors that are used to measure blood chemistry. These size limitations are in large part due to physical geometries of the sensors and the connections to the sensors.

Point of care blood gas analyzers permit in vitro analysis at the patient's bedside, in the emergency room, or in the intensive care unit. These units use solid state sensors with thin-film electrodes. The microchips, reagents, calibrators, and a sampling device are all contained within a disposable cartridge system. Healthcare facilities can select cartridges with additional test options, including potassium, glucose, BUN and lactate. Because whole blood can be tested, minimal specimen processing is needed; the sample does not have to be centrifuged and the plasma separated from the red blood cells prior to testing.

In settings with medium-to high volume sample testing, a multi-use cartridge system is used. These cartridges can be customized to the specific analyte menu and to the volume of testing. The number of samples measured on a cartridge may vary from <NUM> to <NUM> and once loaded into the analyzer, the cartridge typically has an in-use life of between <NUM> and <NUM> days.

The basic principle of operation for blood gas analyzers has not changed significantly from earlier units. In about <NUM> self-contained cartridges were introduced into several analytical systems, paving the way for point of care testing and compact units. Whole blood can be analyzed for many analytes, including the electrolytes potassium (K+), sodium (Na+), and calcium (Ca<NUM>+) and metabolites such as glucose, lactate, blood urea nitrogen (BUN), and creatine. The sensors used for these measurements are ion-specific or ion-selective electrodes (ISE). These sensors are membrane-based electrochemical transducers that respond to a specific ion. Biosensors are used in analyzers in the traditional clinical laboratory, but also in point-of-care testing devices. Biosensors convert the biochemical signal into an electrical signal. <CIT> discloses a microsensor which includes a piezoelectric vibrator as a single sensor. <CIT> discloses cartridges, analyzers and systems for analyzing samples. The cartridges are designed to detect/measure a plurality of analytes with a plurality of sensors. <CIT> discloses an apparatus for analyzing fluids. The apparatus includes heaters, pumps light sources and electronic equipment.

Electrolytes are determined by potentiometric measurements, a form of electrochemical analysis. In potentiometry, the potential or voltage is measured between the two electrodes in a solution. These potentials can also be produced when a metal and ions of that metal are present in a solution. By using a membrane that is semipermeable to the ion, different concentrations of the ion can be separated. These systems use a reference and a measuring electrode. A constant voltage is applied to the reference electrode; the difference in voltage between the reference and measuring electrode is used to calculate the concentration of the ion in solution.

Ion-selective electrodes are based on a modification of the principle of potentiometry. The potential difference or electron flow is created by selectively transferring the ion to be measured from the sample solution to the membrane phase. The ion-selective electrode measures the free ion concentration of the desired analyte on a selectively produced membrane. Membranes have a complex composition and contain organic solvents, inert polymers, plasticizers, and ionophores wherein the ionophores are molecules that increase the membrane's permeability to the specific ion.

Amperometric methods measure the current flow produced from oxidation-reduction reactions. Types of amperometry include enzyme electrodes, such as the glucose oxidase method and the Clark pO<NUM> electrode. These types of designs are well known as biosensors and are adaptable for testing in the clinical laboratory as well as for point of care testing. Enzyme-based biosensor technology was first developed to measure blood glucose. A solution of glucose oxidase is placed between the gas permeable membrane of the pO<NUM> electrode and an outer membrane that is semipermeable. Glucose in the blood diffuses through the semipermeable membrane and reacts with the glucose oxidase. Glucose is converted by glucose oxidase to hydrogen peroxide and gluconic acid.

A polarizing voltage is applied to the electrode, which oxidizes the hydrogen peroxide and contributes to the loss of electrons. Oxygen is consumed near the surface of the pO<NUM> electrode and its rate of consumption is measured. The loss of electrons and rate of decrease of pO<NUM> is directly proportional to the glucose concentration in the sample. Enzyme-based biosensors are also used to measure cholesterol, creatine, and pyruvate.

The basic principles of operation for laboratory blood gas analyzers are the same as for the previously described electrodes for pH, pCO<NUM>, and pO<NUM>; and ion specific electrodes for the measurement of electrolytes. Approximately <NUM>-<NUM>µl of a well-mixed arterial blood sample are typically aspirated through the inlet and sample probe into the measuring chamber. The specimen then contacts the surface of each electrode for several seconds.

One of the principal challenges with existing sensor assemblies is that performing blood analysis using a small blood sample is important when a relatively large number of samples must be taken in a relatively short amount of time or if the volume of blood is limited, as in neonates.

Accordingly, it would be desirable to provide a sensor assembly which remains accurate over a relatively long period of exposure to electrolytes and blood samples, uses a very small sample size, detects the concentration of a number of different electrolytes as well as the partial pressure of a number of blood gases all in a single analysis.

Heel sticks and draws from arterial lines are the most commonly used sites for blood draws. Heel sticks require a high degree of technical expertise to be done properly and without inflicting unnecessary pain or harm to the patient. Frequent blood draws for laboratory testing create the risk of iatrogenic anemia. It has been estimated that <NUM> % of infants < <NUM> receive transfusions for anemia due in part to frequent or excessive blood draws. With a plasma volume of <NUM>-<NUM> % of body weight, a <NUM>,<NUM> infant has a total of <NUM> of plasma. Blood transfusion may be required when <NUM>% or more of a neonate's blood volume is withdrawn in <NUM>-<NUM> days. This amount represents about <NUM>/kg of body weight for a full-term infant, and about <NUM>/kg for a preterm infant.

The volume and number of blood draws have been reduced in recent years due to transcutaneous monitoring and newer equipment. Minimizing the volume of blood draws reduces the subsequent need for transfusion as well as the risk associated with transfusion. Many of the current clinical chemistry analyzers require small blood sample volumes for testing, with many sensor arrays requiring between 45µL to 400µL, depending on the number of analytes being measured (e.g., blood gases, electrolytes, etc.). The hematocrit of an infant can be > <NUM> %, reducing the volume of serum or plasma in the collection container. The "dead volume", consisting of the volume of specimen that must be in the instrument's sampling container, is required in addition to the specimen volume and must be minimal for neonatal applications.

It is an object of the sensor assembly disclosed herein to provide a low cost disposable sensor assembly.

It is a further object of the sensor assembly disclosed herein to compactly provide a disposable sensor assembly capable of housing a large number of analyte sensors.

It is a further object of the sensor assembly disclosed herein to provide a sensor assembly that requires a blood volume of about 30µL. To achieve these objects, the present invention provides a sensor assembly in accordance with claim <NUM>.

Illustrative embodiments of the disclosed technology are described in detail below with reference to the attached drawing figures:.

Disclosed herein is an overhead sensor assembly <NUM> for determining partial pressures of gases, concentrations of electrolytes and metabolites in a fluid sample. Fluids, such as whole blood, can be analyzed for many analytes, including the electrolytes potassium (K+), sodium (Na+), and calcium (Ca<NUM>+) and metabolites such as glucose, lactate, blood urea nitrogen (BUN), and creatine. The sensors used for these measurements are ion-specific or ion-selective electrodes.

The sensor assembly <NUM> is a component that is utilized within a cartridge that is wholly replaceable after a set number of fluid analyses have taken place or after the passage of a set amount of time. Disclosed herein is a subcomponent assembly that is central to the analysis of the fluid, and most importantly, is configured to minimize the volume of fluid, such as whole blood, that is required for analysis. Minimizing the volume of blood required for analysis is central to the inventive concept disclosed herein.

As seen in <FIG>, a sensor assembly <NUM> for analysis of physical parameters and chemical constituents of small volume samples of bodily fluids is disclosed. The assembly <NUM> comprises a sensor panel <NUM> with an upper surface <NUM> and a lower surface <NUM> and at least two analyte sensors <NUM> located on the lower surface <NUM>. The sensor panel <NUM> is preferably fabricated on a ceramic substrate; however, an engineered plastic substrate would function equally as well. The sensor assembly <NUM> utilizes an adhesive layer <NUM> with an upper surface <NUM> and a lower surface <NUM>. The adhesive layer <NUM> utilizes first and second longitudinal edges <NUM>, <NUM> and a contoured fluid pathway cutout <NUM> spanning proximate the first and second longitudinal edges <NUM>, <NUM>. The upper surface <NUM> of the adhesive layer <NUM> is adhesively secured to the lower surface <NUM> of the sensor panel <NUM>. The lower surface <NUM> of the adhesive layer <NUM> is secured to an inset bed <NUM> of the sensor cartridge base <NUM>. This disclosure contemplates that the adhesive layer <NUM> is optional and functionality of the sensor assembly10 is not adversely impacted by elimination of the adhesive layer <NUM>.

<FIG> reveals the sensor cartridge base <NUM> with a fluid inlet <NUM> and a fluid outlet <NUM> and a contoured fluid pathway <NUM> extending between the inlet <NUM> and the outlet <NUM>. A set of coordinates revealing the X, Y and Z directions are also shown in <FIG> and serve to provide a basis for identifying orientation of a feature or claim element throughout this disclosure. The contoured fluid pathway <NUM> mirrors the shape and span of the contoured fluid pathway cutout <NUM> of the optional adhesive layer <NUM>. A fluid sample <NUM> is input at the fluid inlet <NUM> and traverses along the fluid pathway <NUM> for contact with the at least one analyte sensor <NUM> before exiting at the fluid outlet <NUM>.

The volumetric capacity of the contoured fluid pathway <NUM> between the fluid inlet <NUM> and the fluid outlet <NUM> is in the range of from about <NUM> to 35µl which is a de minimis amount. The need for a very small volume of fluid, as previously detailed, is central to this invention as blood draws from neonates, in particular, have been a significant driver for smaller blood volume analytical technologies.

Accompanying each analyte sensors <NUM> are at least two analyte sensor contacts <NUM>. The sensor panel analyte contacts <NUM> are preferably located on the upper surface <NUM> of the sensor panel <NUM> and are laterally and oppositely disposed from one another across the contoured fluid pathway <NUM>. Alternatively, the sensor contacts <NUM> may be located on the lower surface <NUM> of the sensor panel as is indicated in <FIG>.

The sensor contacts <NUM> will be engaged by prepositioned leads (not shown) within the sensor cartridge assembly (not shown). A critical feature of the disclosed assembly is that dimensions of the contoured fluid pathway <NUM> increases, in one or both of the Y and Z directions, in close proximity to an analyte sensor <NUM> and reduces, in one or both of the Y and Z directions, when transitioning between analyte sensors. An exemplary transition area <NUM>, between analyte sensors, can be seen in <FIG> and <FIG>. This narrowed transition area <NUM> between sensors <NUM> facilitates the reduced need for fluid volume in order to perform the desired analysis of the fluid. In an embodiment, the dimensions of the contoured fluid pathway <NUM> increases in the Y direction, in close proximity to an analyte sensor <NUM> and reduces in Y direction, when transitioning between analyte sensors while the dimension in the Z axis remains constant throughout the flow path. In a variation of this embodiment, the dimensions of the contoured flow path in the Z axis may also increase and decease along with the dimensions in the Y axis. In yet another illustrative embodiment, the dimensions of the contoured fluid pathway <NUM> increases in the Z direction, in close proximity to an analyte sensor <NUM> and reduces in Z direction, when transitioning between analyte sensors while the dimension in the Y axis remains constant throughout the flow path. In a variation of this embodiment, the dimensions of the contoured flow path in the Y axis may also increase and decease along with the dimensions in the Z axis.

<FIG> reveals an exemplary sectional view of <FIG> at sectional line <NUM>-<NUM>. The sectional view at <FIG> reveals a rounded fluid flow path <NUM>. Alternative configurations of the fluid flow path <NUM> are also contemplated by this disclosure. For example, a square, rectangular or, hexagonally shaped fluid flow path, among others, are also fully contemplated. The contoured fluid pathway <NUM> is comprised of a first upper edge <NUM> and a second upper edge <NUM>. These edges <NUM>, <NUM> are at the intersection of the walls of the fluid flow pathway <NUM> and the inset bed <NUM> of the cartridge base <NUM>. The widest span between the first edge <NUM> and the second edge <NUM> is preferably in the range of about <NUM> to <NUM>; however, dimensions outside of this range are also contemplated by this disclosure.

<FIG> reveals a view of <FIG> at sectional line <NUM>-<NUM>, at a point where the contoured fluid pathway narrows substantially such as the area seen at reference number <NUM> in <FIG>. The contoured fluid pathway <NUM> in this instance is comprised of a first upper edge <NUM> and a second upper edge <NUM>. These edges <NUM>, <NUM> are at the intersection of the walls of the fluid flow pathway <NUM> and the inset bed <NUM> of the cartridge base <NUM>. This narrowest span between the first upper edge <NUM> and the second upper edge <NUM> is in the range of <NUM> to <NUM> and the depth of the contoured fluid pathway <NUM> from the narrowest cross section to the widest cross section is in the range of from <NUM> to <NUM>.

The contoured fluid pathway <NUM> oscillates between a wider and narrower <NUM> span along the entire length of the pathway in order to minimize the amount of fluid required to pass beneath the analyte sensors <NUM> and yet maintain a sufficiently unrestricted fluidic connection in order to sustain fluid pressure to facilitate conveyance through the sensor assembly <NUM>.

Though the term "beneath" may be used in describing the orientation of the fluid flow path <NUM> relative to the sensor location, this disclosure contemplates that the fluid flow path <NUM> may also be located above the analyte sensors <NUM> and the term "beneath" should not be considered limiting in that respect. The fluid path widens when in proximity to a sensor because a certain minimum surface area of the analyte sensor <NUM> must contact the fluid in order to take a reading. Where there are no sensors in the fluid path, there are no such surface area requirements and the fluid path narrows.

As seen in <FIG> the sensor assembly <NUM> is capable of analyzing a wide range of constituent concentrations and fluid parameters. The sensor assembly <NUM> disclosed herein includes analyte sensors <NUM> capable of measuring, for example, pCO<NUM>, O<NUM>, BUN, Na, Cre, K, Ca, Lac, Mg, Glu, Cl and pH. Though the sensors <NUM> are identified in a particular order in <FIG>, this disclosure contemplates that the sensors may be ordered in many different configurations without impacting the functionality of the fluid analyzer.

The above listed parameters are measured by many blood analyzers. <FIG> reveals a perspective view of how the fluid would appear as it traverses, in the X direction, through the contoured fluid pathway <NUM> of the sensor cartridge base <NUM>. As previously discussed, the fluid pathway increases in the Y and Z directions, growing larger in both dimensions, when in proximity to the analyte sensors <NUM> and lessens, decreasing in dimension in the Y and Z directions, when traversing between the sensors <NUM> thereby minimizing the sample volume necessary to perform the analysis. <FIG> reveals a view from beneath the fluid path providing additional detail on the narrowing and widening profile of the fluid pathway <NUM>. Where there are no sensors in the fluid path, there are no sensor surface area requirements thereby allowing the fluid path to lessen dimensionally as detailed immediately above.

In operation, the fluid, typically blood, is withdrawn from a patient generally via a syringe or other standard blood draw technique. As previously detailed, the blood draw is very minimal in volume, generally no greater than <NUM>µl. The fluid <NUM> is then aspirated into the fluid inlet port <NUM>. Upon entering the fluid inlet port <NUM>, the fluid <NUM> traverses along the contoured fluid pathway <NUM>. This traverse along the fluid pathway <NUM> places the fluid beneath one, and preferably a multitude of analyte sensors <NUM>, capable of detecting either a change in voltage or amperage.

Claim 1:
A sensor assembly (<NUM>) for analysis of physical parameters and chemical constituents of small volume samples of bodily fluids, the assembly comprising:
a sensor panel (<NUM>) with an upper surface (<NUM>) and a lower surface (<NUM>) and at least two analyte sensors (<NUM>) located on the lower surface (<NUM>);
a sensor cartridge base (<NUM>) with a fluid inlet (<NUM>) and outlet (<NUM>) and a contoured fluid pathway (<NUM>) extending between the inlet (<NUM>) and the outlet (<NUM>), wherein the contoured fluid pathway (<NUM>) expands in proximity to each analyte sensor (<NUM>) and narrows when traversing away from each analyte sensor (<NUM>), and as a fluid sample is input at the fluid inlet (<NUM>), the fluid traverses along the fluid pathway (<NUM>) in contact with the at least one analyte sensor (<NUM>), characterized in that
the sensor assembly (<NUM>) further comprises an adhesive layer (<NUM>) with a tacky upper (<NUM>) and lower surface (<NUM>), first (<NUM>) and second longitudinal edges (<NUM>) and a contoured fluid pathway cutout (<NUM>) spanning proximate the first (<NUM>) and second longitudinal edges (<NUM>), the upper surface (<NUM>) of the adhesive layer (<NUM>) secured to the lower surface (<NUM>) of the sensor panel (<NUM>);
and wherein the volumetric capacity of the contoured fluid pathway (<NUM>) between the fluid inlet (<NUM>) and the fluid outlet (<NUM>) is in the range of from <NUM> to 35µl.