SARS-CoV-2
has infected over 128 million people worldwide, and
until a vaccine is developed and widely disseminated, vigilant testing
and contact tracing are the most effective ways to slow the spread
of COVID-19. Typical clinical testing only confirms the presence or
absence of the virus, but rather, a simple and rapid testing procedure
that sequences the entire genome would be impactful and allow for
tracing the spread of the virus and variants, as well as the appearance
of new variants. However, traditional short read sequencing methods
are time consuming and expensive. Herein, we describe a tiled genome
array that we developed for rapid and inexpensive full viral genome
resequencing, and we have applied our SARS-CoV-2-specific genome tiling
array to rapidly and accurately resequence the viral genome from eight
clinical samples. We have resequenced eight samples acquired from
patients in Wyoming that tested positive for SARS-CoV-2. We were ultimately
able to sequence over 95% of the genome of each sample with greater
than 99.9% average accuracy.
Current
techniques for making high-resolution, photolithographic
DNA microarrays suffer from the limitation that the 3′ end
of each sequence is anchored to a hard substrate and hence is unavailable
for many potential enzymatic reactions. Here, we demonstrate a technique
that inverts the entire microarray into a hydrogel. This method preserves
the spatial fidelity of the original pattern while simultaneously
removing incorrectly synthesized oligomers that are inherent to all
other microarray fabrication strategies. First, a standard 5′-up
microarray on a donor wafer is synthesized, in which each oligo is
anchored with a cleavable linker at the 3′ end and an Acrydite
phosphoramidite at the 5′ end. Following the synthesis of the
array, an acrylamide monomer solution is applied to the donor wafer,
and an acrylamide-silanized acceptor wafer is placed on top. As the
polyacrylamide hydrogel forms between the two wafers, it covalently
incorporates the acrydite-terminated sequences into the matrix. Finally,
the oligos are released from the donor wafer upon immersing in an
ammonia solution that cleaves the 3′-linkers, thus freeing
the oligos at the 3′ end. The array is now presented 3′-up
on the surface of the gel-coated acceptor wafer. Various types of
on-gel enzymatic reactions demonstrate a versatile and robust platform
that can easily be constructed with far more molecular complexity
than traditional photolithographic arrays by endowing the system with
multiple enzymatic substrates. We produce a new generation of microarrays
where highly ordered, purified oligos are inverted 3′-up, in
a biocompatible soft hydrogel, and functional with respect to a wide
variety of programable enzymatic reactions.
Low-temperature Aluminum-Germanium (Al-Ge) eutectic bonding has been investigated for monolithic threedimensional integrated circuits (3DIC) applications. Successful bonds using Al-Ge bilayer films as thin as 157 nm were achieved at temperatures as low as 435 °C, when applying 200 kPa downpressure for 30 minutes. The liquid phase of the eutectic composition ensured a seamless and void-free bond. The fracture energy of the Al-Ge bond (630 nm thick) was measured to be G c = 50.5 ± 12.7 J/m 2 , using double cantilever beam thin-film adhesion measurement technique. An array of silicon islands was attached onto an amorphous SiO 2 wafer using low-temperature Al-Ge bonding. These islands could be used to form devices on upper layers of monolithically integrated 3DICs.Index Terms-wafer bonding, monolithic integration, Al-Ge eutectic, 3DIC.
In this article, the authors present and discuss the fabrication of three-dimensional ͑3D͒ optical phased array ͑OPA͒ devices for large angle, two-dimensional optical beam steering. Fabrication of a single layer ͑one-dimensional͒ OPA prototype for one-dimensional beam steering on silicon nanomembrane is presented. The authors present different approaches, such as nanoimprint lithography, optical lithography, and self-aligned patterning of multibonded silicon-on-insulator wafers, for the realization of 3D OPA devices in particular and 3D photonic circuits in general. At the end, the authors discuss the challenges and potential solutions.
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