Pattern recognition of shape-encoded hydrogel biosensor arrays

Abstract

A pattern-recognition and encoding system has been developed for a biochip platform using shaped hydrogel sensors batch produced via photolithography. Each sensor shape is fashioned with a unique pattern of dots that makes it identifiable to a pattern recognition system. By linking the sensor's function to its shape, "random" arrays can be created ͑i.e., arrays that do not require sensors to be located at specific positions͒. Random arraying can be quickly and cost-effectively achieved via self-assembly methods. Pattern-recognition software was written to perform automated recognition of micrographs exhibiting fluorescing sensors. As a test of the recognition process, an array of shapeencoded DNA sensors was fabricated using lithography. Fluorescent micrographs were taken of a DNA-sensing experiment, and then processed with the pattern-recognition software. The results show that this process is quite viable with 98% recognition accuracy of the nondefective sensors in both images.

Hydrogel microparticles from lithographic processes: Novel materials for fundamental and applied colloid science

“…These systems form a valuable complement of materials for use in a wide variety of applications in biotechnology and high-performance materials. Moreover, co-polymerization of multiple different hydrogel pre-cursors, either by the use of co-polymers in the precursor itself or by random co-polymerization during lithographic processing, provides an additional degree of flexibility in the synthesis of hydrogel colloids, and has been used to create particles with highly tunable equilibrium and dynamic properties, including swelling [29], biodegradation [28], and self-assembly [30]. …”

“…The simplest photolithographic methods involve pattern transfer into a stationary fluid film or reservoir [29,42,56] prepared in a manner similar to that used in imprint lithography. Recently, a number of so-called “flow lithography” techniques have been introduced, in which photolithography is performed in situ within a microfluidic environment [23].…”

“…For chemically cross-linked polymers, the mesh size can be controlled by tuning the composition of the hydrogel precursor. Specifically, the concentration and molecular weight of the monomer and/or cross-linking agent have been used to tune the mesh size of polymer hydrogels [29,58]. Although it is difficult (if not impossible) to directly observe the mesh size or microporous structure of the hydrogel, many indirect methods exist to estimate the mesh size of cross-linked polymers, including scattering [14], equilibrium swelling [1], and probe diffusivity measurements [58,75].…”

“…Shape-encoded hydrogel particles called MUFFINS (mesoscale unaddressed functionalized features indexed by shape) represent the first generation of colloidal microgel biosensors [29]. A single contact photolithography step was used to reproducibly synthesize batches of PEG-based colloids functionalized with either single stranded-DNA or cell-expressed antibody fragments for the capture of fluorescently-labeled complementary DNA sequence and hapten, respectively.…”

Hydrogel microparticles for biosensing

“…For graphical encoding in particular, imaging enables capture of complex information about the particle shape or bit-code (extruded regions) in a single acquisition. However, examples of automated particle decoding based on image analysis are rare [119] and decoding is often manual.…”