Massively Parallel Selection of NanoCluster Beacons

Yu An Kuo; Cheulhee Jung; Yu An Chen; Hung Che Kuo; Oliver S. Zhao; Trung D. Nguyen; James R. Rybarski; Soonwoo Hong; Yuan I. Chen; Dennis C. Wylie; John A. Hawkins; Jada N. Walker; Samuel W.J. Shields; Jennifer S. Brodbelt; Jeffrey T. Petty; Ilya J. Finkelstein; Hsin Chih Yeh

doi:10.1002/adma.202204957

Massively Parallel Selection of NanoCluster Beacons

Yu An Kuo, Cheulhee Jung, Yu An Chen, Hung Che Kuo, Oliver S. Zhao, Trung D. Nguyen, James R. Rybarski, Soonwoo Hong, Yuan I. Chen, Dennis C. Wylie, John A. Hawkins, Jada N. Walker, Samuel W.J. Shields, Jennifer S. Brodbelt, Jeffrey T. Petty, Ilya J. Finkelstein, Hsin Chih Yeh

Department of Biotechnology

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

NanoCluster Beacons (NCBs) are multicolor silver nanocluster probes whose fluorescence can be activated or tuned by a proximal DNA strand called the activator. While a single-nucleotide difference in a pair of activators can lead to drastically different activation outcomes, termed polar opposite twins (POTs), it is difficult to discover new POT-NCBs using the conventional low-throughput characterization approaches. Here, a high-throughput selection method is reported that takes advantage of repurposed next-generation-sequencing chips to screen the activation fluorescence of ≈40 000 activator sequences. It is found that the nucleobases at positions 7–12 of the 18-nucleotide-long activator are critical to creating bright NCBs and positions 4–6 and 2–4 are hotspots to generate yellow–orange and red POTs, respectively. Based on these findings, a “zipper-bag” model is proposed that can explain how these hotspots facilitate the formation of distinct silver cluster chromophores and alter their chemical yields. Combining high-throughput screening with machine-learning algorithms, a pipeline is established to design bright and multicolor NCBs in silico.

Original language	English
Article number	2204957
Journal	Advanced Materials
Volume	34
Issue number	41
DOIs	https://doi.org/10.1002/adma.202204957
Publication status	Published - 2022 Oct 13

Keywords

fluorescent nanomaterials
high-throughput screening
NanoCluster Beacons
next-generation sequencing
silver nanoclusters

ASJC Scopus subject areas

Materials Science(all)
Mechanics of Materials
Mechanical Engineering

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10.1002/adma.202204957

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Kuo, Y. A., Jung, C., Chen, Y. A., Kuo, H. C., Zhao, O. S., Nguyen, T. D., Rybarski, J. R., Hong, S., Chen, Y. I., Wylie, D. C., Hawkins, J. A., Walker, J. N., Shields, S. W. J., Brodbelt, J. S., Petty, J. T., Finkelstein, I. J., & Yeh, H. C. (2022). Massively Parallel Selection of NanoCluster Beacons. Advanced Materials, 34(41), [2204957]. https://doi.org/10.1002/adma.202204957

@article{39b5f08f27a64ad5a04af395a132a798,

title = "Massively Parallel Selection of NanoCluster Beacons",

abstract = "NanoCluster Beacons (NCBs) are multicolor silver nanocluster probes whose fluorescence can be activated or tuned by a proximal DNA strand called the activator. While a single-nucleotide difference in a pair of activators can lead to drastically different activation outcomes, termed polar opposite twins (POTs), it is difficult to discover new POT-NCBs using the conventional low-throughput characterization approaches. Here, a high-throughput selection method is reported that takes advantage of repurposed next-generation-sequencing chips to screen the activation fluorescence of ≈40 000 activator sequences. It is found that the nucleobases at positions 7–12 of the 18-nucleotide-long activator are critical to creating bright NCBs and positions 4–6 and 2–4 are hotspots to generate yellow–orange and red POTs, respectively. Based on these findings, a “zipper-bag” model is proposed that can explain how these hotspots facilitate the formation of distinct silver cluster chromophores and alter their chemical yields. Combining high-throughput screening with machine-learning algorithms, a pipeline is established to design bright and multicolor NCBs in silico.",

keywords = "fluorescent nanomaterials, high-throughput screening, NanoCluster Beacons, next-generation sequencing, silver nanoclusters",

author = "Kuo, {Yu An} and Cheulhee Jung and Chen, {Yu An} and Kuo, {Hung Che} and Zhao, {Oliver S.} and Nguyen, {Trung D.} and Rybarski, {James R.} and Soonwoo Hong and Chen, {Yuan I.} and Wylie, {Dennis C.} and Hawkins, {John A.} and Walker, {Jada N.} and Shields, {Samuel W.J.} and Brodbelt, {Jennifer S.} and Petty, {Jeffrey T.} and Finkelstein, {Ilya J.} and Yeh, {Hsin Chih}",

note = "Funding Information: This work was supported by the Welch Foundation to J.S.B. (F-1155), H.-C.Y. (F-1833), and I.J.F. (F-1808), the Texas 4000 to H.-C.Y., National Institutes of Health to H.-C.Y. and I.J.F. (GM129617), National Science Foundation to H.-C.Y. (CBET2041345) and J.S.B. (CBET2029266), and a UT-Austin Catalyst Grant to I.J.F. Funding Information: This work was supported by the Welch Foundation to J.S.B. (F‐1155), H.‐C.Y. (F‐1833), and I.J.F. (F‐1808), the Texas 4000 to H.‐C.Y., National Institutes of Health to H.‐C.Y. and I.J.F. (GM129617), National Science Foundation to H.‐C.Y. (CBET2041345) and J.S.B. (CBET2029266), and a UT‐Austin Catalyst Grant to I.J.F. Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2022",

month = oct,

day = "13",

doi = "10.1002/adma.202204957",

language = "English",

volume = "34",

journal = "Advanced Materials",

issn = "0935-9648",

publisher = "Wiley-VCH Verlag",

number = "41",

}

TY - JOUR

T1 - Massively Parallel Selection of NanoCluster Beacons

AU - Kuo, Yu An

AU - Jung, Cheulhee

AU - Chen, Yu An

AU - Kuo, Hung Che

AU - Zhao, Oliver S.

AU - Nguyen, Trung D.

AU - Rybarski, James R.

AU - Hong, Soonwoo

AU - Chen, Yuan I.

AU - Wylie, Dennis C.

AU - Hawkins, John A.

AU - Walker, Jada N.

AU - Shields, Samuel W.J.

AU - Brodbelt, Jennifer S.

AU - Petty, Jeffrey T.

AU - Finkelstein, Ilya J.

AU - Yeh, Hsin Chih

N1 - Funding Information: This work was supported by the Welch Foundation to J.S.B. (F-1155), H.-C.Y. (F-1833), and I.J.F. (F-1808), the Texas 4000 to H.-C.Y., National Institutes of Health to H.-C.Y. and I.J.F. (GM129617), National Science Foundation to H.-C.Y. (CBET2041345) and J.S.B. (CBET2029266), and a UT-Austin Catalyst Grant to I.J.F. Funding Information: This work was supported by the Welch Foundation to J.S.B. (F‐1155), H.‐C.Y. (F‐1833), and I.J.F. (F‐1808), the Texas 4000 to H.‐C.Y., National Institutes of Health to H.‐C.Y. and I.J.F. (GM129617), National Science Foundation to H.‐C.Y. (CBET2041345) and J.S.B. (CBET2029266), and a UT‐Austin Catalyst Grant to I.J.F. Publisher Copyright: © 2022 Wiley-VCH GmbH.

PY - 2022/10/13

Y1 - 2022/10/13

N2 - NanoCluster Beacons (NCBs) are multicolor silver nanocluster probes whose fluorescence can be activated or tuned by a proximal DNA strand called the activator. While a single-nucleotide difference in a pair of activators can lead to drastically different activation outcomes, termed polar opposite twins (POTs), it is difficult to discover new POT-NCBs using the conventional low-throughput characterization approaches. Here, a high-throughput selection method is reported that takes advantage of repurposed next-generation-sequencing chips to screen the activation fluorescence of ≈40 000 activator sequences. It is found that the nucleobases at positions 7–12 of the 18-nucleotide-long activator are critical to creating bright NCBs and positions 4–6 and 2–4 are hotspots to generate yellow–orange and red POTs, respectively. Based on these findings, a “zipper-bag” model is proposed that can explain how these hotspots facilitate the formation of distinct silver cluster chromophores and alter their chemical yields. Combining high-throughput screening with machine-learning algorithms, a pipeline is established to design bright and multicolor NCBs in silico.

AB - NanoCluster Beacons (NCBs) are multicolor silver nanocluster probes whose fluorescence can be activated or tuned by a proximal DNA strand called the activator. While a single-nucleotide difference in a pair of activators can lead to drastically different activation outcomes, termed polar opposite twins (POTs), it is difficult to discover new POT-NCBs using the conventional low-throughput characterization approaches. Here, a high-throughput selection method is reported that takes advantage of repurposed next-generation-sequencing chips to screen the activation fluorescence of ≈40 000 activator sequences. It is found that the nucleobases at positions 7–12 of the 18-nucleotide-long activator are critical to creating bright NCBs and positions 4–6 and 2–4 are hotspots to generate yellow–orange and red POTs, respectively. Based on these findings, a “zipper-bag” model is proposed that can explain how these hotspots facilitate the formation of distinct silver cluster chromophores and alter their chemical yields. Combining high-throughput screening with machine-learning algorithms, a pipeline is established to design bright and multicolor NCBs in silico.

KW - fluorescent nanomaterials

KW - high-throughput screening

KW - NanoCluster Beacons

KW - next-generation sequencing

KW - silver nanoclusters

UR - http://www.scopus.com/inward/record.url?scp=85137492105&partnerID=8YFLogxK

U2 - 10.1002/adma.202204957

DO - 10.1002/adma.202204957

M3 - Article

C2 - 35945159

AN - SCOPUS:85137492105

SN - 0935-9648

VL - 34

JO - Advanced Materials

JF - Advanced Materials

IS - 41

M1 - 2204957

ER -

Massively Parallel Selection of NanoCluster Beacons

Abstract

Keywords

ASJC Scopus subject areas

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