STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

BACKGROUND

A sensor, also called a detector, is a device that measures a physical quantity and converts it to a signal which may be read by an observer or by an instrument. Sensors are used in chemical and biochemical testing to determine characteristics of an analyte of interest within a specimen or sample.

Sensor arrays, in which multiple sensors are grouped into a single unit, are useful in chemistry and medicine to determine the presence and/or concentration of multiple target analytes. For example, various types of analytical tests related to patient diagnosis and therapy can be performed by analysis of a liquid sample taken from a patient. Bodily fluids commonly tested include urine, blood, plasma, saliva, cerebrospinal fluid, pleural fluid, and the like. Blood samples, for example, are routinely analyzed to obtain measurements of the partial pressures of CO2and O2and concentrations of electrolytes and metabolites in the blood. Specifically, potentiometric sensors are often employed which can utilize an ion-selective electrode or an electrode having an ion-permeable membrane that selectively permits the ion of interest to diffuse through. The operating principle is based on the measureable potential difference that is created when an ion equilibrates between two phases.

In vitro diagnostic sensors are typically housed within clinical diagnostic instruments for simultaneous analysis of a large number of analytes. Currently, single-use sensors and multi-use sensors are available for use in sensor arrays, such as the sensor arrays set forth in U.S. Publication Nos. 2015/0082874 and 2011/0286888 and International Publication No. WO 2015/155665 (the entire contents of each of which are hereby expressly incorporated herein by reference).

Sensors which detect analytes having a biological component, such as cells, protein, or nucleic acid, are referred to as biosensors. One example of target analyte assays amenable to biosensor measurement include the use of enzymes that can detect the target analyte. In general, an enzyme is deposited on an electrode and “held in place” by cross-linking into an insoluble form for entrapment in a polymer. A cover membrane is then typically applied to further retain the enzyme and provide protection from fouling, interferents, etc. Particular (but non-limiting) examples of target analytes detectable by this type of biosensor include blood urea nitrogen (BUN), glucose, glutamate, lactate, ethanol, ascorbic acid, choline acetylcholine, creatinine, cholesterol, pyruvate, bilirubin, and the like.

Another example of in vitro diagnostic sensors currently in use is the ion selective electrode (ISE). ISEs are used to determine the presence and quantity of various ion analytes in biological samples and have become useful diagnostic techniques. Indeed, ISEs have been used to detect ion analytes such as (but not limited to) magnesium, sodium, potassium, calcium, chloride, and the like.

A number of different analyzers currently exist for making such measurements utilizing rigid layered sensor assemblies and electrical circuits. Such sensor assemblies are used to assess the condition of medical patients through primary clinical indications. Because of the frequency with which many patients are tested, the ability to use small sample sizes for performing analysis is desirable. Patients in intensive care units may require a sampling frequency of 15-20 per day for blood gas and clinical chemistry measurements. In these cases, analyzing small sample volumes is desirable, due to the relatively large number of samples taken in a relatively short period of time. Further, to limit the number of tests performed, it is desirable to gather as much information as possible with each test.

In particular, at the Point-of-Care (POC), there is a need for in vitro diagnostic (IVD) platforms that provide clinical results by using the smallest sample volume as possible. Typical currently available IVD systems require a minimum sample volume of 100 μL of whole blood to complete a full analysis. In some settings, 100 μL is too large of a sample, particularly in the neonatal intensive care unit (NICU). This has driven the need to reduce the size of the technologies used to make the measurements in IVD platforms and to create different types of substrates on which chemistries are applied.

Methods of producing in vitro diagnostic sensors are well known in the art, and these methods typically utilize chemistries that apply a sensing membrane to a surface of a substrate (such as, but not limited to, ceramic or glass). A gasket can be used to hold the membranes in place while being housed in various types of modules and arrays. In order to reduce complexity and sample size, new module designs have been created that do not utilize a gasket. These sensor production technologies typically utilize various additional layers of other materials that must be applied to the substrates to help improve adhesion; the mechanism of adhesion utilized in these is passive (i.e., electrostatic).

It has been shown that the catecholic amino acid 3,4-dihydroxyphenylalanine (DOPA) is the primary functional group in Mussel foot proteins (Mfps) and is responsible for the adhesive capability of the mollusk mussel (Dalsin et al.,Langmuir, (2005) 21:640-646; and Forooshani et al.,J. Polym. Sci., Part A: Polym. Chem. (2017) 55:9-33; the entire contents of each of which are expressly incorporated herein by reference); as disclosed therein, modified polymers containing the catecholic functional group (1,2-dihydroxybenzene), for example DOPA, or alternatively dopamine (3,4-dihydroxyphenethylamine), have been synthesized for new adhesives or glues that exhibit strong adhesion to a range of surfaces, including under long term exposure to aqueous environments. DOPA has been used to create surface-binding cell adhesion polypeptides and antifouling adhesive copolymers for cardiovascular stents (US Patent Application Publication No. 2009/0018642 and U.S. Pat. No. 7,927,620; the entire contents of which are incorporated herein by reference). In addition, DOPA modified linear polymers are disclosed in U.S. Pat. No. 7,622,533 (the entire contents of which are incorporated herein by reference).

