Testing for diseases, such as infectious disease speciation and antibiotic resistance profiling, often requires interrogating samples for many dozens of biomarkers. Electronic readout from such large arrays of biosensors has been hampered by the difficulty in generating and addressing large arrays of electrode-based sensors on inexpensive, passive chips. Arrays of biosensors can be generated to work in conjunction with electrochemical reporter systems, enabling multiplexing and detection of analytes in a single chip. Doing so, however, often results in an assay that includes tens, hundreds, or even thousands of electrodes. This large number of electrodes poses a problem for minimizing chip sizes (and hence, manufacturing costs and portability) if each electrode must be coupled to an external contact in order to be independently addressable.
While it is possible to reduce the number of external electrical contacts by sharing such contacts among multiple electrodes through multiplexing, known approaches for doing so pose additional problems. For example, the need for independently-addressed electrical contacts corresponding to each sensor, as well as reference and counter electrodes, requires that highly multiplexed arrays employ an active multiplexing strategy. The additional complexity of integrated active electronics has effectively limited current multiplexed detection systems to a small set of contacts (and hence, low levels of multiplexing) that rely on passive switching mechanisms. Moreover, the design of such chips often leads to substantial electrical cross-talk, which can reduce the overall sensitivity and specificity of detection.
There is therefore a need for improved electrochemical detection systems, devices, and mechanisms.