Today, physiological samples such as for example body fluids may be analyzed for a wide variety of biochemical analytes. Accurate medical diagnostics is an important part of medical treatment such as the identification of health conditions and disease, monitoring, prognosis, and companion diagnostics. There are two main settings in which medical diagnostics systems are used: dedicated medical laboratories and the so-called point-of-care (PoC) testing.
The term “physiological sample” in the context of this description shall comprise all liquid, solid or gaseous material that is either biological material obtained from the patient, such as blood, urine, stool, or tissue, or samples that are prepared for subsequent analysis based on such biological material.
Laboratory diagnostic devices as used in medical laboratories generally provide a wide variety of analytical capabilities. For example, devices sold by Illumina and Affymetrix provide molecular diagnostics of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Clinical analysers, such as those sold by Roche and Abbott, provide tests for immunochemistry (antibody based detection) and clinical chemistry (detection of small chemical molecules). Devices as sold for example by Beckman Coulter can count cells in body fluids.
Such diagnostic devices are sensitive, accurate and flexible, and provide a high throughput. However, they also have the disadvantage of being expensive, and requiring well trained personnel for operation. For this reason such diagnostic devices are mainly used in hospital laboratories and centralized medical laboratories, where they can be used most efficiently. However, since such devices require a physiological sample from a patient, said samples have to be transported to the medical laboratory, where the analysis is going to be performed. As a result, the results of the analysis are available only after hours or even days.
An increasingly large number of diagnostic tests are carried out at the point of care, close to the patient, for example in a medical practice, an emergency room of a hospital, an ambulance vehicle, or even at the patient's side. Point-of-care diagnostic devices are often portable, and capable of obtaining analytical results rapidly (within minutes). Their use is generally much simpler, so that the diagnostic tests can be carried out by ordinary medical personnel or even the patient himself.
The most widespread point-of-care diagnostic devices perform lateral flow immunoassay strip tests. Such tests are available for a wide variety of diagnostic indications such as pregnancy, HIV, malaria, influenza testing. Corresponding devices are provided from a multitude of manufacturers, such as e.g. Swiss Precision Diagnostics, Alere, Bayer, and Siemens. The lateral flow test is usually limited to the detection of one or two analytes and qualitative detection, for example a clear colour change.
The Alere Triage MeterPro system is an immunochemistry system composed of an assay unit in the form of a consumable cartridge and an evaluation device in the form of a reusable bench-top reader. Cartridges are available to detect panels of biomarkers such as a three-protein cardiac panel (Myoglobin, CK-MB and Troponin I), and a drug-screening panel. Thus such a cartridge allows the simultaneous testing of a sample for three analytes. Every new panel of biomarkers requires a new test cartridge. The Alere epoc system and Abott i-STAT system have cartridges that may measure panels of blood gases, electrolytes, and metabolites. For the Abott i-STAT system, cartridges are available that measure single cardiac biomarkers (Troponin I, CK-MB, or BNP). These devices are sensitive and accurate. A main limitation is the high price per tested analyte, compared to laboratory diagnostic machines. Another disadvantage is the limited variety of available test cartridges.
New biosensor systems allow multiplexed detection of a large number of analytes for point-of-care diagnostic applications. Such devices offer advanced and integrated analytical capabilities, rivalling those of laboratory diagnostic devices.
The Gyros Lab-on-a-CD system and the Advanced Liquid Logic digital microfluidic system are capable of detecting over 100 analytes at a time, using a bench-top analyser. Other biosensing approaches for detecting various biochemical analytes are provided for example in U.S. Pat. No. 5,719,324, WO2002/048701, U.S. Pat. No. 4,020,830, WO89/009938, U.S. Pat. Nos. 4,945,045, and 5,641,640.
Medical diagnostics devices typically consist of a reusable measuring device and a consumable component (test unit or reagents). A user wishing to carry out a certain diagnostic test will select a diagnostics device having the required analytical capabilities. For example, a diabetes mellitus patient wanting to know the glucose concentration in his blood, may use a dedicated diagnostic system comprising a reusable blood glucose meter and a consumable blood glucose test strip.
If an evaluation device allows to perform different diagnostic tests, the user will have to choose the corresponding consumable assay unit. For example, a user wanting to test for myocardial infarction may use an Alere Triage meter (evaluation device) and a Cardio 3 Panel cartridge (assay unit) to test for three cardiac biomarkers. A user wanting to test for other analytes such as further cardiac biomarkers, will have to select other test cartridges that can perform the required diagnostic tests.
The costs for the consumable assay units are not primarily defined by the mere actual production costs, but on one side by the R&D costs to be recovered by the manufacturer, and on the other side by the health insurance reimbursement tariffs applicable on a certain diagnostic test for a certain analyte, which generally differ between countries and/or insurance companies, etc. Thus the purchasing price for a certain assay unit will depend on the analytical capabilities, such as the number and the kind of analytes that can measured by the consumable assay unit.
Such an approach of recovering costs via the purchasing price of the assay unit works for consumable assay units capable of measuring one analyte, or a few analytes.
Combinations of analytes are available only for tests that are routinely needed together, such combined tests for cardiac biomarkers or drug abuse screenings. Thus, generally only few different diagnostic combination tests are available.
The purchase prize approach does not provide an optimal solution for diagnostic systems providing extended multiplexing capabilities, as discussed above, when used for point-of-care diagnostics, with reusable evaluation device and consumable assay unit. For example, the application of a diagnostic system that can test for a hundred analytes at the same time would be cost prohibitive, since the purchase prize would depend on the R&D costs and the reimbursement tariffs of said hundred analyte tests, although the manufacturing costs of the consumable assay unit are comparable to assay units with much less diagnostic capabilities.
Medical diagnostics systems are increasingly integrated in data communication networks, allowing the exchange of data between hospitals, medical practices, centralized laboratories, the patient's home, and even mobile units such as ambulance vehicles or rescue helicopters. Medical diagnostics systems capable of communicating with electronic health care management systems further provide a variety of benefits for ordering, billing, calibrating, and synchronizing test results with electronic health records. In all such applications, however, confidentiality of sensitive private medical data is an issue.
US2002/0161606, US2005/0055240 and U.S. Pat. No. 6,018,713 describe systems for ordering diagnostic tests from centralized clinical laboratories. Said systems are based on a client terminal and a remote server in a centralized laboratory. The user enters patient information, selects and orders diagnostic tests to be carried out by the centralized laboratory. Reports on the results of the diagnostic tests can be sent to the client terminal. The performed tests can be automatically charged to a health insurance company. Although having certain logistical advantages, the disclosed systems still have the common problem of centralized laboratories, namely the necessity of samples having to be transported to the laboratory, in order to carry out the diagnostic tests.
EP1776919 discloses a subscription-based biosensor monitoring system. The system allows biosensor measurements to be conducted using a reusable meter device and consumable test strips only when a subscription is active. The meter device communicates its identifier code and ROM circuit identifier code to a remote server, which verifies that the subscription is active, and enables the meter device to conduct the diagnostic tests.
WO99/022236 proposes a cellular network based calibration method for blood glucose test strips. A meter device that is coupled to a mobile telephone measures the result of the diagnostic test performed on the test strip, and communicates the results and an identification code of the test strip to a remote server. The remote server transmits the calibration data associated to the test strip to the mobile telephone, which then calculates the final test results. The disclosed system does not protect the privacy of test results.
US2004/0181528 shows an inventory management system for point-of-care devices. The electronic system tracks a plurality of point-of-care diagnostics devices in regard to their expiry date, consumption time, room temperature storage time, and manages the ordering of additional devices to replenish inventory. The disclosed system is limited to inventory management, and the replenishment of inventory when diagnostic devices are no longer useable.
WO02/100261 describes a system for point-of-care in-vitro blood analysis. The system is based on a modified smart card that can conduct biosensing tests. The smart card is inserted into a smart card reader, which measures an analog output signal, converts the analog signal to a digital signal, and sends said digital raw data to a general purpose computer device to produce analytical results. The disclosed system is limited to modified smartcard based biosensors, and can only produce analytical results with the help of a general purpose computer.
The unauthorized or fraudulent access to sensitive personal health care data, which includes analytical results, is a major safety and privacy concern.
US 2012/0029303 A1 discloses a virtual medical examination system comprising a remote patient device, and a diagnostic device, which can communicate wirelessly, by wire, or via a network. The diagnostic device, e.g. a camera, generates diagnostic results, e.g. pictures, and transmits said result data to the remote patient device, which encrypts the data and transmits the encrypted data to a patient record server. The medical personnel using the diagnostic device have access to the diagnostic data. The purpose of the system is to provide real-time remote virtual medical examination.
In U.S. Pat. No. 7,039,810 B1, one or more implanted medical devices communicate wirelessly with a local computer (“programmer”) that allows to program the implanted medical device. The programmer provides an encrypted data connection to a remote expert data centre.
US 2005/065890 A1 discloses a method to securely distribute media content such as movies, for example for media players in airplanes, or via set top boxes, and the like. In one embodiment, media content data (e.g. a movie) are encrypted with a content key. This content key is again encrypted with a public key of a specific media player, for each authorized media player. The multitude of encrypted content keys for all media players are distributed together with the encrypted content data. Each authorized media player can decrypt the content key previously encrypted with its own specific public key, but cannot decrypt the other encrypted content keys. This allows to securely distribute an identical, protected media content data set to a large number of authorized receivers, without the need of producing individually secured data carriers for each receiver, and without the need of contacting a remote authorization server. In another variant, the media content data are split up in a number of data partitions. Of each partition, two or more copies are provided, each partition copy having a unique fingerprint. All those partitions are encrypted with a different content key. For each authorized media player, a unique combination of partitions representing the complete media content is provided, and the corresponding individual content key set is encrypted with the public key of the authorized media player. The encrypted media content is distributed together with all encrypted content key sets of all authorized media players. Once decrypted, the complete media content data set has a unique fingerprint. As a result, illegal copies of the content can be traced back to a specific media player. In all disclosed variants, identical protected content is distributed and made accessible to a multitude of predefined authorized recipients. Neither the content to be made accessible, nor the list of recipients can be changed in the process.
WO 02/01271 A1 discloses a method for selectively encrypting and decrypting different sections of an electronic document, which allows to provide selective access levels to groups of authorized users to different sections of the document. Users in a group with a certain access level know the private key of this level, and can access those sections of a document that have been previously encrypted with the corresponding public key of this certain access level. Sections of different access level may also be convoluted. Thus, of a section with a first access level, a certain subsection with a second access level is encrypted with a second public key, and then the complete section including the encrypted subsection is encrypted with the first public key. The assignment between the different sections of encrypted content and the user groups corresponding to a certain access level is static.
There is a general need for diagnostics systems that allow the cost efficient use of multiplexed diagnostic tests for point-of-care applications, so that the advantages of such multiplexed diagnostic tests can be fully exploited.