Home Beijing SpermCatcher Biotech Co., Ltd. Leverages Optical Tweezers to Enable Non-invasive Live Cell Isolation Starting from Sperm Selection

Beijing SpermCatcher Biotech Co., Ltd. Leverages Optical Tweezers to Enable Non-invasive Live Cell Isolation Starting from Sperm Selection

Aug 10, 2023 08:00 CST Updated 08:00

Preface: Although the name of Beijing Bujingzhe Biotechnology Co., Ltd. translates to “Sperm Hunter,” please do not assume that the company’s business is limited solely to sperm selection for assisted reproduction.


In fact, by integrating “optical tweezers + (ultra-)high-resolution imaging + artificial intelligence,” the company has developed a technology for “label-free, non-invasive capture and analysis of live cells,” which can be applied in various live-cell capture scenarios across healthcare, animal husbandry, cell biology, and other fields.Sperm cells are the most difficult to capture, analyze, and select among all cell types, representing the forefront of technological advancement. Indeed, label-free, non-destructive capture of live sperm serves as a flagship demonstration of cutting-edge technology.


Assisted reproduction is merely the first wave stirred up by this technological leviathan as it sets sail into the vast, trillion-dollar blue ocean of industry...


Originating from “Seeking the Way at Mount Qingcheng, Paying Homage to the Waters of Dujiangyan”


Years later, whenever the origins of the “Sperm Catcher” were discussed, Fang Yaliang would always recount his experience attending a conference in Chengdu in October 2016.

 

At that time, due to a schedule change for the conference, there were several hours to spare before their flight departed from Chengdu. Fang Yaliang therefore joined Professor Li Wei, a Distinguished Young Scholar and recipient of the Chinese Academy of Sciences’ “Hundred Talents Program,” in climbing Mount Qingcheng.

 

During the hike, the two engaged in an in-depth discussion about a global challenge in assisted reproductive technology: sperm selection for optimal motility and morphology, specifically how to identify a single high-quality sperm that can be directly used for in vitro fertilization (IVF).

 

Amidst the vast, mist-shrouded peaks of Mount Qingcheng, the Dragon Carriage arrives to seek wisdom from the Yellow Emperor. Unaware of the passing hours, the two companions conversed all the way from the foot of the mountain to its summit, and then back down again. “We felt neither the swift passage of time nor any sense of fatigue.” Still eager to continue their discussion, they proceeded on to Dujiangyan, where their dialogue carried on with undiminished enthusiasm.

 

“We spent nearly five to six hours in discussion, essentially thoroughly covering this topic (sperm selection),” Fang Yaliang told VCBeat with a hint of excitement. “Our initial idea was straightforward: to leverage ‘optical tweezers combined with computer-assisted analysis’ technology to address the global challenge of effectively selecting viable single sperm in assisted reproduction.”

 

Optical Tweezers: As the name suggests, optical tweezers are tools that utilize light (focused laser beams) to trap microscopic objects. They can clamp, manipulate, and perform micro-processing on tiny entities such as cells, organelles, and biological macromolecules. Serving as the sole tool for manipulating living organisms ranging from tens of nanometers to tens of micrometers in size, optical tweezers exhibit exceptional compatibility and cause no damage to biological materials, making them a revolutionary means for studying life processes at the microscopic level.

 

Although the term “optical tweezers” includes the word “tweezers,” they do not operate like conventional tweezers used in daily life, which require physical compression at the tips to grasp objects. Their advantage lies in employing a non-contact “optical trapping” mechanism that avoids damage, enabling precise capture of live cells in motion. Specifically, in sperm selection, optical tweezers can immobilize sperm without causing mechanical injury, thereby supporting the selection process and significantly improving both the success rate and efficiency of sperm selection.

 

Upon returning from Chengdu, Fang Yaliang immediately embarked on demonstrating the technical feasibility. Through the introduction of Professor Li Wei, Fang Yaliang met Researcher Jiang Yuqiang, Chief Scientist at the Imaging Center of the Institute of Genetics, Chinese Academy of Sciences, and a scientist under the CAS Hundred Talents Program. The two engaged in sustained, in-depth, and detailed discussions on the technical approach.


To further substantiate the clinical need and prevent a disconnect between technology and clinical requirements, Fang Yaliang consulted numerous professors in the field of assisted reproductive technology (ART). After seeking advice from Professor Huang Xuefeng, Director of the Reproductive Medicine Center at the First Affiliated Hospital of Wenzhou Medical University—one of the first five ART centers approved in China—and recognizing Professor Huang’s nod of approval (Professor Huang is a renowned “triple-threat” expert in male infertility, female infertility, and embryology laboratory techniques within China’s ART community), the “Sperm Catcher” project officially embarked on its entrepreneurial journey.

 

SpermSeeker entrusted the YU Qiang team with the system design and development of its sperm selection system. In April 2018, SpermSeeker received funding from the Beijing Municipal Science & Technology Commission for the “Beijing Medical Collaborative Innovation Research Project,” which was successfully completed in 2021. In October of the same year, American scientist Arthur Ashkin was awarded the Nobel Prize in Physics for optical tweezers and their applications in biological systems. Later, Professor Yang Ge, who had spent about a decade at Carnegie Mellon University conducting research on cellular bioimage processing and informatics, joined the R&D team to lead image processing and artificial intelligence efforts. Professors Li Wei and Huang Xuefeng became SpermSeeker’s clinical technical advisors. The company has now established a robust R&D team integrating experts in optical imaging, artificial intelligence, genetics, and clinical practice.

 

Whether it was the enchanting journey of “Seeking the Way at Mount Qingcheng and Paying Homage to the Waters of Dujiangyan,” receiving funding from the “Beijing Medical Collaborative Innovation Research Project,” or the 2018 Nobel Prize awarded for optical tweezers and their application in biological systems, this indescribable serendipity and sense of destiny have firmly convinced the sperm-capturing researchers that “our product will surely succeed!”


"Optical Tweezers + (Ultra-)High-Resolution Imaging + Artificial Intelligence Technology,"

A solution that simultaneously assesses vitality and morphology within 15 seconds, ready for immediate use upon optimal selection.


Sperm must be viable to achieve successful in vitro fertilization (IVF). Sperm with abnormal morphology, often associated with high DNA fragmentation rates, can adversely affect clinical outcomes in assisted reproduction and may even lead to miscarriage.

 

A routine semen specimen contains not only spermatozoa but also seminal plasma, epithelial cells, red blood cells, white blood cells, bacteria, and spermatozoa at various stages of their life cycles. Currently, sperm selection primarily involves using technical methods to remove impurities from the semen and isolate spermatozoa for use in IVF (in vitro fertilization and embryo transfer) or ICSI (intracytoplasmic sperm injection).

 

Common methods for sperm selection in assisted reproduction include processing semen according to WHO guidelines, followed by manual microscopic selection by embryologists or intracytoplasmic morphologically selected sperm injection (IMSI). However, regardless of the method employed, all require manual operation by embryologists. The entire process can be described as “navigating a labyrinthine quest for the finest essence, where each layer presents its own formidable challenge.”

 

First, becoming a qualified embryologist requires at least four to five years of training. The training cycle for embryologists is long, there is a significant talent shortage, and the work intensity is high. Second, ICSI involves selecting a single sperm with robust motility and favorable morphology from a large population of continuously moving sperm. Currently, the most common method is for embryologists to visually assess sperm under a microscope; however, this approach is highly subjective and relies heavily on the embryologist’s experience. Furthermore, during the sperm selection process, manual manipulation by embryologists inevitably introduces individual variability, making quality control challenging. This is particularly problematic for patients with oligoasthenozoospermia, where the time-consuming nature of optimal sperm selection hinders improvements in clinical workflow efficiency.

 

Beijing Sperm Catcher Biotechnology Co., Ltd. is an innovative medical device manufacturer and a technical platform service provider for live-cell capture and analysis research instruments, integrating industry, academia, research, and engineering. The company brings together top experts from multidisciplinary fields including artificial intelligence, optics, biophysics, clinical medicine, genetics, and automation, focusing on the development and application of innovative live-cell products in the areas of clinical medicine, life sciences, and livestock breeding.

 

“AI-Powered Live Sperm Selection Workstation” is Catcher’s inaugural product and the world’s first device offering a one-stop, comprehensive solution that enables label-free imaging of individual live sperm, intelligent analysis, and non-destructive capture for immediate downstream use. It represents the most challenging and representative frontier technology currently available for non-destructive live-cell capture.

  

"AI-Powered Live Sperm Selection Workstation" Developed by Bu Jing Zhe

 

“AI-Powered Live Sperm Selection Workstation” consists of an optical imaging module, an optical tweezers module, a micromanipulation module, a temperature control module, and AI-based live sperm analysis and control software. By tightly integrating optical tweezers, (ultra-)high-resolution imaging, and artificial intelligence technologies, the system classifies sperm based on their motility characteristics and structural features to achieve automated selection. It can identify and isolate a single live sperm from a large population of continuously moving live sperm in under 15 seconds per analysis, while simultaneously measuring the vitality, morphology, and structure of the same live sperm. The system offers the advantages of label-free imaging, intelligent analysis, and non-destructive capture, and it preserves the vitality and morphological data of the selected sperm for clinical use and traceability.

 

Fang Yaliang told VCBeat that the “AI-Based Live Sperm Selection Workstation” has intelligently achieved the selection of single live sperm with intact viability and meeting morphological and motility criteria from a large population of continuously moving live sperm, for direct use in intracytoplasmic sperm injection (ICSI) during assisted reproduction; similarly, it can alsoAchieve the “leap from destructive methods to non-invasive acquisition of viable cells,” enabling the clinical and research application of “obtaining viable, uninfected cells that most closely reflect true physiological values,” and truly realizing the mission of technology serving the public.

 

Notably, in September 2022, according to relevant documents issued by the National Medical Products Administration (NMPA), the AI-based workstation for selecting viable sperm was classified as a Class III medical device, with classification code 18-07.This means that, in the future, devices of this type will not need to undergo repeated classification and determination; they can be directly classified and registered by referencing this code. The “AI-Based Live Sperm Selection Workstation” has become a pioneering innovator for this category of instruments and equipment.


It is reported that the workstation’s preclinical studies are nearing completion, and clinical registration will be initiated shortly.

 

Leveraging optical tweezers as the foundational technology, integrated with imaging and artificial intelligence, to drive advancements across healthcare, animal husbandry, scientific research, and other broad fields.


Leveraging the integrated technology of “optical tweezers + (super-)high-resolution imaging + artificial intelligence,” SpermCatcher has not only established its own competitive moat but also defined its core value proposition—namely, building capabilities in “live-cell imaging and capture” combined with “AI-driven analysis of live-cell images.” This capability does not require invasive separation techniques such as staining or antigen–antibody assays; instead, by applying deep learning algorithms to labeled images of target cells, it can be extended to virtually every application scenario involving live-cell selection.

 

In the sperm collector’s roadmap, optimized selection of sperm for assisted reproduction is merely the first step in a long journey of applying this technology.


Benefiting from the ability to individually select, capture, and transfer active suspended cells based on imaging.


  • In the medical field,This technology can be applied not only to sperm selection in assisted reproduction but also to the isolation and application of live cells in other medical fields;

  • In the field of life sciences,It can be used for spectral identification and classification of different cells, differentiation and screening of stem cells, development and screening of organoids, and selection of single cells or micro/nanoparticles.

  • In the field of livestock breeding,It can be applied in the breeding of cattle, pigs, rare animals, and other plants and animals.

 

Following the development of the “Artificial Intelligence Live Sperm Selection Workstation,” and based on optimized innovations to the existing architectural model,The “AI-Based Live Bovine Sperm Sex-Sorting Workstation” is under development, with the potential to break through the decades-long monopoly and blockade imposed by hundreds of international patents on bovine frozen semen production.Achieving Label-Free Identification of Bovine X- and Y-Chromosome-Bearing Sperm by Analyzing Their “Vitality,” Providing a Powerful Tool to Address Critical Technological Bottlenecks and Promote High-Quality Development in the Livestock Industry.

 

“Optical tweezers enable the trapping of micro- and nano-particles without direct contact or mechanical damage. Combined with the rapid advancements in artificial intelligence (AI) technology, I believe that the effective integration of optical tweezers and AI will create a new frontier, much like the applications of PCR and sequencing technologies. It will permeate various industries, become a new mainstream applied technology, and drive the development of cell biology.” Fang Yaliang has long envisioned the developmental trajectory of “Sperm Catcher.”

 

“Regarding the technical architecture model for live-cell imaging, analysis, and capture, SpermHunter has completed all technological breakthroughs over nearly eight years; what remains is to conduct validation experiments on various other types of live cells.”"In the future, we will operate Bujingzhe as a platform technology company, aiming to incubate various companies in specialized fields on Bujingzhe's technological platform."“Perhaps, ‘SpermHunter’ will be renamed to better reflect its technical features—label-free imaging of micro- and nano-cells, intelligent analysis, and non-destructive capture. Alternatively, all core technologies may be consolidated under a newly established parent company, with ‘SpermHunter’ becoming a company focused exclusively on assisted reproduction. This strategic direction will be determined in the course of future development.”

 

Currently, Bu Jing Zhe is seeking a new round of financing and recruiting distributors for scientific research instruments to advance the clinical validation, registration, and approval of its existing products, as well as the construction of a big data graph database. The company aims to expand production and formally provide equipment and technical services to the scientific research community.

 

Whether discussing the saying “Seek the Way at Mount Qingcheng, Pay Homage to the Waters of Dujiangyan,” introducing his company’s technological products, or recalling the bottlenecks and challenges encountered during research and development, Fang Yaliang’s voice becomes loud and resonant whenever “Sperm Catcher” is mentioned. He speaks endlessly, with a cheerful and blissful tone that resembles singing. Although this author could only hear his voice through the receiver, I am convinced that the man on the other end of the line—both in his eyes and in his heart—still radiates the same intense and scorching light as he did on that afternoon in 2016…