Automatic high-throughput and non-invasive selection of sperm at the biochemical level

Yaoqin Mu; Xiaoyu Zhou; Longjie Li; Xiaowen Liu; Xu Wen; Lei Zhang; Bei Yan; Wei Zhang; Kejun Dong; Hao Hu; Yangwei Liao; Zhengxin Ye; Aimin Deng; Yuan Wang; Zenghui Mao; Mengsu Yang; Xianjin Xiao

doi:10.1016/j.medj.2024.03.008

Automatic high-throughput and non-invasive selection of sperm at the biochemical level

Yaoqin Mu
, Xiaoyu Zhou
, Longjie Li
, Xiaowen Liu
, Xu Wen
, Lei Zhang
, Bei Yan
, Wei Zhang
, Kejun Dong
, Hao Hu
, Yangwei Liao
, Zhengxin Ye
, Aimin Deng
, Yuan Wang
, Zenghui Mao^*
, Mengsu Yang^*
, Xianjin Xiao^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

3 Citations (Scopus)

74 Downloads (CityUHK Scholars)

Abstract

Background: Sperm selection, a key step in assisted reproductive technology (ART), has long been restrained at the preliminary physical level (morphology or motility); however, subsequent fertilization and embryogenesis are complicated biochemical processes. Such an enormous “gap” poses tough problems for couples dealing with infertility, especially patients with severe/total asthenozoospermia.

Methods: We developed a biochemical-level, automatic-screening/separation, smart droplet-TO-hydrogel chip (BLASTO-chip) for sperm selection. The droplet can sense the pH change caused by sperm's respiration products and then transforms into a hydrogel to be selected out.

Findings: The BLASTO-chip system can select biochemically active sperm with an accuracy of over 90%, and its selection efficiency can be flexibly tuned by nearly 10-fold. All the substances in the system were proven to be biosafe via evaluating mice fertilization and offspring health. Live sperm down to 1% could be enriched by over 76-fold to 76%. For clinical application to patients with severe/total asthenozoospermia, the BLASTO-chip could select live sperm from human semen samples containing 10% live but 100% immotile sperm. The rates of fertilization, cleavage, early embryos, and blastocysts were drastically elevated from 15% to 70.83%, 10% to 62.5%, 5% to 37.5%, and 0% to 16.67%, respectively.

Conclusions: The BLASTO-chip represents a real biochemical-level technology for sperm selection that is completely independent of sperm's motility. It can be a powerful tool in ART, especially for patients with severe/total asthenozoospermia.

Funding: This work was funded by the Ministry of Science and Technology of China, the Ministry of Education of China, and the Shenzhen-Hong Kong Hetao Cooperation Zone.

Original language	English
Pages (from-to)	603-621, e1-e7
Journal	Med
Volume	5
Issue number	6
Online published	11 Apr 2024
DOIs	https://doi.org/10.1016/j.medj.2024.03.008
Publication status	Published - 14 Jun 2024

Funding

We thank all members of Changsha Maternal and Child Health Hospital for providing human oocytes and sperm samples. We thank Z.S. Yin from Huazhong Agricultural University for technical assistance in the animal experiment. All figures in this study were created with BioRender.com. X.X. was supported by the National Key Research and Development Program (nos. 2023YFE0210200 and 2021YFC2701402) and the interdisciplinary research program of HUST Science Park. M.Y. was supported by the Hong Kong Innovation and Technology Fund, the Mainland-Hong Kong Joint Funding Scheme (Platform) (no. MHP/240/23), the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project (no. HZQB-KCZYZ-2021017), and the National Key Research and Development Program of China (no. 2018YFA0901104). X.Z. was supported by the central government-guided special funds for local scientific and technological development (no. 226Z2603G). Z.M. was supported by the Hunan Province Assisted Reproduction and Regenerative Medicine Clinical Demonstration Center Funded Project (no. 2020SK4019), the Research Plan Project of Hunan Provincial Health Commission (no. 202205033867), the General Project of Hunan Natural Science Foundation (no. 2022JJ30628), and the Hunan Provincial Science and Technology Innovation Plan Project (no. 2021SK53207). L.L. was supported by the open research fund of the Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control (no. HPKL2023019) and the Natural Science Foundation of Hubei Province of China (no. 2023AFB402). X.X. conceived the idea of this work. Y.M. X.Z. and L.L. designed the research strategy, contributed to data collection, and developed the methodology. X.X. M.Y. and Z.M. administered the project. Y.W. X.L. X.W. L.Z. B.Y. W.Z. K.D. H.H. Y.L. and Z.Y. conducted related experiments and investigations. Y.M. X.Z. and L.L. performed and oversaw statistical analyses. Y.M. and X.X. had unrestricted access to all data. Y.M. X.Z. L.L. X.X. M.Y. and Z.M. drafted the original manuscript and contributed to its review and editing. All authors approved the final manuscript and take full responsibility for its content, including data accuracy and adherence to the registered protocol and statistical analysis. The authors declare no competing interests. We thank all members of Changsha Maternal and Child Health Hospital for providing human oocytes and sperm samples. We thank Z.S. Yin from Huazhong Agricultural University for technical assistance in the animal experiment. All figures in this study were created with BioRender.com. X.X. was supported by the National Key Research and Development Program (nos. 2023YFE0210200 and 2021YFC2701402 ) and the interdisciplinary research program of HUST Science Park . Y.M. was supported by the Hong Kong Innovation and Technology Fund , the Mainland-Hong Kong Joint Funding Scheme (Platform) (no. MHP/240/23 ), the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project (no. HZQB-KCZYZ-2021017 ), and the National Key Research and Development Program of China (no. 2018YFA0901104 ). X.Z. was supported by the central government-guided special funds for local scientific and technological development (no. 226Z2603G). Z.M. was supported by the Hunan Province Assisted Reproduction and Regenerative Medicine Clinical Demonstration Center Funded Project (no. 2020SK4019 ), the Research Plan Project of Hunan Provincial Health Commission (no. 202205033867 ), the General Project of Hunan Natural Science Foundation (no. 2022JJ30628 ), and the Hunan Provincial Science and Technology Innovation Plan Project (no. 2021SK53207 ). L.L. was supported by the open research fund of the Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control (no. HPKL2023019 ) and the Natural Science Foundation of Hubei Province of China (no. 2023AFB402 ).

Research Keywords

asthenozoospermia
biochemical level
Foundational research
microfluidic
sperm selection

Publisher's Copyright Statement

This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

Access Output

10.1016/j.medj.2024.03.008

214733619.pdfFinal Published version, 6.02 MBLicence: CC BY-NC-ND

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

@article{044b9a07ae374ab0ab3a40f09a4db6a6,

title = "Automatic high-throughput and non-invasive selection of sperm at the biochemical level",

abstract = "Background: Sperm selection, a key step in assisted reproductive technology (ART), has long been restrained at the preliminary physical level (morphology or motility); however, subsequent fertilization and embryogenesis are complicated biochemical processes. Such an enormous “gap” poses tough problems for couples dealing with infertility, especially patients with severe/total asthenozoospermia. Methods: We developed a biochemical-level, automatic-screening/separation, smart droplet-TO-hydrogel chip (BLASTO-chip) for sperm selection. The droplet can sense the pH change caused by sperm's respiration products and then transforms into a hydrogel to be selected out. Findings: The BLASTO-chip system can select biochemically active sperm with an accuracy of over 90\%, and its selection efficiency can be flexibly tuned by nearly 10-fold. All the substances in the system were proven to be biosafe via evaluating mice fertilization and offspring health. Live sperm down to 1\% could be enriched by over 76-fold to 76\%. For clinical application to patients with severe/total asthenozoospermia, the BLASTO-chip could select live sperm from human semen samples containing 10\% live but 100\% immotile sperm. The rates of fertilization, cleavage, early embryos, and blastocysts were drastically elevated from 15\% to 70.83\%, 10\% to 62.5\%, 5\% to 37.5\%, and 0\% to 16.67\%, respectively. Conclusions: The BLASTO-chip represents a real biochemical-level technology for sperm selection that is completely independent of sperm's motility. It can be a powerful tool in ART, especially for patients with severe/total asthenozoospermia. Funding: This work was funded by the Ministry of Science and Technology of China, the Ministry of Education of China, and the Shenzhen-Hong Kong Hetao Cooperation Zone.{\textcopyright} 2024 The Author(s). Published by Elsevier Inc.",

keywords = "asthenozoospermia, biochemical level, Foundational research, microfluidic, sperm selection",

author = "Yaoqin Mu and Xiaoyu Zhou and Longjie Li and Xiaowen Liu and Xu Wen and Lei Zhang and Bei Yan and Wei Zhang and Kejun Dong and Hao Hu and Yangwei Liao and Zhengxin Ye and Aimin Deng and Yuan Wang and Zenghui Mao and Mengsu Yang and Xianjin Xiao",

year = "2024",

month = jun,

day = "14",

doi = "10.1016/j.medj.2024.03.008",

language = "English",

volume = "5",

pages = "603--621, e1--e7",

journal = "Med",

issn = "2666-6359",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Automatic high-throughput and non-invasive selection of sperm at the biochemical level

AU - Mu, Yaoqin

AU - Zhou, Xiaoyu

AU - Li, Longjie

AU - Liu, Xiaowen

AU - Wen, Xu

AU - Zhang, Lei

AU - Yan, Bei

AU - Zhang, Wei

AU - Dong, Kejun

AU - Hu, Hao

AU - Liao, Yangwei

AU - Ye, Zhengxin

AU - Deng, Aimin

AU - Wang, Yuan

AU - Mao, Zenghui

AU - Yang, Mengsu

AU - Xiao, Xianjin

PY - 2024/6/14

Y1 - 2024/6/14

N2 - Background: Sperm selection, a key step in assisted reproductive technology (ART), has long been restrained at the preliminary physical level (morphology or motility); however, subsequent fertilization and embryogenesis are complicated biochemical processes. Such an enormous “gap” poses tough problems for couples dealing with infertility, especially patients with severe/total asthenozoospermia. Methods: We developed a biochemical-level, automatic-screening/separation, smart droplet-TO-hydrogel chip (BLASTO-chip) for sperm selection. The droplet can sense the pH change caused by sperm's respiration products and then transforms into a hydrogel to be selected out. Findings: The BLASTO-chip system can select biochemically active sperm with an accuracy of over 90%, and its selection efficiency can be flexibly tuned by nearly 10-fold. All the substances in the system were proven to be biosafe via evaluating mice fertilization and offspring health. Live sperm down to 1% could be enriched by over 76-fold to 76%. For clinical application to patients with severe/total asthenozoospermia, the BLASTO-chip could select live sperm from human semen samples containing 10% live but 100% immotile sperm. The rates of fertilization, cleavage, early embryos, and blastocysts were drastically elevated from 15% to 70.83%, 10% to 62.5%, 5% to 37.5%, and 0% to 16.67%, respectively. Conclusions: The BLASTO-chip represents a real biochemical-level technology for sperm selection that is completely independent of sperm's motility. It can be a powerful tool in ART, especially for patients with severe/total asthenozoospermia. Funding: This work was funded by the Ministry of Science and Technology of China, the Ministry of Education of China, and the Shenzhen-Hong Kong Hetao Cooperation Zone.© 2024 The Author(s). Published by Elsevier Inc.

AB - Background: Sperm selection, a key step in assisted reproductive technology (ART), has long been restrained at the preliminary physical level (morphology or motility); however, subsequent fertilization and embryogenesis are complicated biochemical processes. Such an enormous “gap” poses tough problems for couples dealing with infertility, especially patients with severe/total asthenozoospermia. Methods: We developed a biochemical-level, automatic-screening/separation, smart droplet-TO-hydrogel chip (BLASTO-chip) for sperm selection. The droplet can sense the pH change caused by sperm's respiration products and then transforms into a hydrogel to be selected out. Findings: The BLASTO-chip system can select biochemically active sperm with an accuracy of over 90%, and its selection efficiency can be flexibly tuned by nearly 10-fold. All the substances in the system were proven to be biosafe via evaluating mice fertilization and offspring health. Live sperm down to 1% could be enriched by over 76-fold to 76%. For clinical application to patients with severe/total asthenozoospermia, the BLASTO-chip could select live sperm from human semen samples containing 10% live but 100% immotile sperm. The rates of fertilization, cleavage, early embryos, and blastocysts were drastically elevated from 15% to 70.83%, 10% to 62.5%, 5% to 37.5%, and 0% to 16.67%, respectively. Conclusions: The BLASTO-chip represents a real biochemical-level technology for sperm selection that is completely independent of sperm's motility. It can be a powerful tool in ART, especially for patients with severe/total asthenozoospermia. Funding: This work was funded by the Ministry of Science and Technology of China, the Ministry of Education of China, and the Shenzhen-Hong Kong Hetao Cooperation Zone.© 2024 The Author(s). Published by Elsevier Inc.

KW - asthenozoospermia

KW - biochemical level

KW - Foundational research

KW - microfluidic

KW - sperm selection

UR - https://www.scopus.com/pages/publications/85191312921

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85191312921&origin=recordpage

U2 - 10.1016/j.medj.2024.03.008

DO - 10.1016/j.medj.2024.03.008

M3 - RGC 21 - Publication in refereed journal

C2 - 38608708

AN - SCOPUS:85191312921

SN - 2666-6359

VL - 5

SP - 603-621, e1-e7

JO - Med

JF - Med

IS - 6

ER -

Automatic high-throughput and non-invasive selection of sperm at the biochemical level

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Cite this