Evidence map›Paper›PMID 35614105›Full record

ArticleNature communications2022

A high-throughput multiparameter screen for accelerated development and optimization of soluble genetically encoded fluorescent biosensors.

Dorothy Koveal, Paul C Rosen, Dylan J Meyer, Carlos Manlio Díaz-García, Yongcheng Wang, Li-Heng Cai, Peter J Chou, David A Weitz, Gary Yellen

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
8.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
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  13. Activity-dependent citrate dynamics in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  17. Mechanism and application of thiol-disulfide redox biosensors with a fluorescence-lifetime readout.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Dorothy KovealDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2907-6925
Paul C RosenDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7414-454X
Dylan J MeyerDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8453-3813
Carlos Manlio Díaz-GarcíaDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4352-2496
Yongcheng WangDepartment of Physics and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Li-Heng CaiDepartment of Physics and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.ORCID 0000-0002-6806-0566
Peter J ChouDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4592-5210
David A WeitzDepartment of Physics and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Gary YellenDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA. gary_yellen@hms.harvard.edu.ORCID 0000-0003-4228-7866
Harvard University · US

Funding

Viral ModuleP30EY012196 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Gabriel Kreiman · 1998 to 2026
$21.3M
High-throughput optimization of genetically-encoded fluorescent biosensorsR01GM124038 · NIGMS · HARVARD MEDICAL SCHOOL · PI YELLEN, GARY I · 2017 to 2025
$2.5M
Novel platforms for development of optimized genetically encoded fluorescent biosensorsF32GM123577 · NIGMS · HARVARD MEDICAL SCHOOL · PI KOVEAL, DOROTHY · 2017 to 2019
$190k
Understanding Compartmentalized Leucine Metabolism Downstream of mTORC1 SignalingF31CA254162 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ROSEN, PAUL · 2020 to 2023
$186k
Metabolic coupling of neuronal ion transportF32NS116105 · NINDS · HARVARD MEDICAL SCHOOL · PI MEYER, DYLAN JOHN · 2020 to 2022
$147k
NCI NIH HHS F31 CA254162NEI NIH HHS P30 EY012196NIGMS NIH HHS F32 GM123577NIGMS NIH HHS R01 GM124038NINDS NIH HHS F32 NS116105
6 · The paper itself

Abstract

Genetically encoded fluorescent biosensors are powerful tools used to track chemical processes in intact biological systems. However, the development and optimization of biosensors remains a challenging and labor-intensive process, primarily due to technical limitations of methods for screening candidate biosensors. Here we describe a screening modality that combines droplet microfluidics and automated fluorescence imaging to provide an order of magnitude increase in screening throughput. Moreover, unlike current techniques that are limited to screening for a single biosensor feature at a time (e.g. brightness), our method enables evaluation of multiple features (e.g. contrast, affinity, specificity) in parallel. Because biosensor features can covary, this capability is essential for rapid optimization. We use this system to generate a high-performance biosensor for lactate that can be used to quantify intracellular lactate concentrations. This biosensor, named LiLac, constitutes a significant advance in metabolite sensing and demonstrates the power of our screening approach.

Indexed as

Biosensing TechniquesColoring AgentsLactatesMicrofluidicsColoring AgentsLactates

Identifiers

PMID35614105
PMCPMC9133083
OpenAlexW4281482663

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.