Evidence map›Paper›PMID 41484238›Full record

ArticleScientific reports2026

A droplet microfluidics-based platform for generating target-specific, natively-paired immune libraries and identifying potent and developable antibodies.

Anusuya Ramasubramanian, Brendan T Deveney, Sarah A Clark, Paula Boutin, Kayla Keepseagle, Saleh Riahi, Taotao Lao, Megan Salemi, Sagar Kathuria, Pep Amengual-Rigo and 15 more

Abstract read
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

25 authors.

Anusuya RamasubramanianLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA. anusuyam_ramasubramanian@dfci.harvard.edu.
Brendan T DeveneyExperimental Soft Condensed Matter Group, School of Engineering and Applied Sciences (SEAS), Harvard University, Cambridge, MA, 02138, USA.
Sarah A ClarkLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Paula BoutinLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Kayla KeepseagleExperimental Soft Condensed Matter Group, School of Engineering and Applied Sciences (SEAS), Harvard University, Cambridge, MA, 02138, USA.
Saleh RiahiLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Taotao LaoLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Megan SalemiLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Sagar KathuriaLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Pep Amengual-RigoLarge Molecule Research Platform Germany, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany.
Dilyana DimovaLarge Molecule Research Platform Germany, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany.
Leighton MarcoviciLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Joern HopkeLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Jocelyn NewtonLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Kalie MixLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Kevin KramerLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Hélène ErasimusLarge Molecule Research Platform France, Sanofi R&D, 13 Quai Jules Guesde, 94403, Vitry-sur-Seine, France.
Norbert FurtmannLarge Molecule Research Platform Germany, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany.
Guillaume MottetLarge Molecule Research Platform France, Sanofi R&D, 13 Quai Jules Guesde, 94403, Vitry-sur-Seine, France.
Nikolai SuslovLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Ankit MahendraLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Sambasiva Rao PemmarajuLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
Partha S ChowdhuryLarge Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA.
David A WeitzExperimental Soft Condensed Matter Group, School of Engineering and Applied Sciences (SEAS), Harvard University, Cambridge, MA, 02138, USA.
John A HeymanExperimental Soft Condensed Matter Group, School of Engineering and Applied Sciences (SEAS), Harvard University, Cambridge, MA, 02138, USA. jheyman@seas.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human antibody repertoire is a promising source for therapeutic-grade antibodies. Yet current methods for strategically mining these B cell repertoires are stymied by throughput and chain pairing considerations. This study presents advancements in fluidics and molecular biology that enable the multi-step encapsulation and capture of B cells from an immunized, humanized mouse in nanoliter sized droplets. Once singularly captured, antigen-specific B-cells can be lysed and individually manipulated via RT-PCR to splice cognate V genes and create a predominantly natively paired library. To explore the importance of these process improvements in library generation, we constructed natively-paired libraries against two therapeutically-relevant human proteins. Through deep sequencing, bioinformatics-driven screening and phage display, we selected functional, target-specific antibodies. Our findings reveal that natively paired libraries contain a higher percentage of target-specific antibodies and demonstrate enhanced potency and improved developability in both in silico and in vitro assessments relative to combinatorial library-derived antibodies. Furthermore, antibodies with native pairing show increased potency as well as improved in silico and in vitro developability compared to their randomly paired counterparts. To this end, we see this droplet microfluidic platform and its capacity to generate and facilitate the high-throughput interrogation of antigen-specific antibody repertoires as an important, orthogonal therapeutic antibody discovery approach.

Indexed as

AntibodiesMicrofluidicsAnimalsB-LymphocytesHumansMicePeptide LibraryAntibodiesPeptide Library

Identifiers

PMID41484238
PMCPMC12852821

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.