Research Achievement

Journal Cover images

cover

Microfluidics for intracellular/subcellular drug delivery in high throughput

Drug Delivery with High Throughput

1. Xiaoyun Ding, Martin P Stewart, Armon Sharei, James Weaver, Robert Langer, Klavs F Jensen, High-throughput nuclear delivery and rapid expression of DNA via mechanical and electrical cell-membrane disruption. Nature  Biomedical Engineering, 0039, (2017).

2. Martin P Stewart, Armon Sharei, Xiaoyun Ding, Gaurav Sahay, Robert Langer, Klavs F Jensen, In vitro and ex vivo strategies for intracellular delivery. Nature 538 (7624), 183-192 (2016)

Nuclear transfection of DNA into mammalian cells is challenging yet critical for many biological and medical studies. Here, by combining cell squeezing and electric-field-driven transport in a device that integrates microfluidic channels with constrictions and microelectrodes, we demonstrate nuclear delivery of plasmid DNA within 1 hour after treatment, the most rapid DNA expression in a high-throughput setting (up to millions of cells per minute per device). Passing cells at high speed through microfluidic constrictions smaller than the cell diameter mechanically disrupts the cell membrane, allowing a subsequent electric field to further disrupt the nuclear envelope and drive DNA molecules into the cytoplasm and nucleus. By tracking the localization of the ESCRT-III (endosomal sorting complexes required for transport) protein CHMP4B, we show that the integrity of the nuclear envelope is recovered within 15 minutes of treatment. We also provide insight into subcellular delivery by comparing the performance of the disruption-and-field-enhanced method with those of conventional chemical, electroporation, and manual-injection systems.

 

Cancer Cell Separation

SAW based Cancer Cell Separation

Xiaoyun Ding, et al., "Cell separation using tilted-angle standing surface acoustic waves" Proceedings of the National Academy of Sciences of the United States of America (PNAS), 111, 12992-12997 (2014).

(Highlighted as a News Report on MIT Home Page. Carnegie Mellon News Daily News. Breast Cancer News Today. Headlines and Global News. The Daily Dot. Medical News Today. Science 2.0. e-Science News Laboratory Equipment R&D Phys Org. Gizmag. Quantum Times. Nanowerk. Science Daily. Daily News. Technobahn. Open Nano. Jersey Tribune. Penn State News.)

We have developed a unique approach for the separation of particles and biological cells through standing surface acoustic waves oriented at an optimum angle to flow direction of cells and particles in a microfluidic device.  This experimental set-up, optimized by systematic analyses, has been used to demonstrate effective separation based on size, compressibility, and mechanical properties of particles and cells.  The potential of this method for biological/biomedical applications was demonstrated through the example of isolating MCF-7 breast cancer cells from white blood cells.  The method offers a possible route for label-free particle or cell separation for many applications in research, disease diagnosis and drug-efficacy assessment.

 

Standing SAW based Acoustic Tweezers

 

Xiaoyun Ding, et al., PNAS, Vol. 109, pp. 11105-11109, 2012. (was reported and highlighted by  Nature MethodsNational Science Foundation, National Institutes of Health Live Science, Big Ten Science, Lab Spaces, One News Page, gantdaily, MSNBC, R&D, Medical News Today, Nanowerk, Science Daily ,Popular Science, Online Journal, Newswise, domain-b, Bio-Medicine, Penn State Live, Penn State Science, Real Clear Science, Sci Tech Update, Phys Org, UPI.com, Softpedia, ALN Magazine, SciTechDaily, Futurity, DVICE, Inside Science, )

We have developed the first acoustic manipulation platform, so-called “acoustic tweezers”, which can trap and dexterously manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) along a programmed route in two-dimensions within a dime-sized microfluidic chip. Fig. 1 A shows the real photo of our acoustic tweezers device. The acoustic tweezers can move a 10-µm single polystyrene bead to write the word “PNAS” (fig.1 B) and a bovine red blood cell to trace the letters “PSU” (fig. 1 C). It was also the first technology capable of touchless trapping and manipulating Caenorhabditis elegans, a one-millimeter long roundworm that is an important model system for studying diseases and development in humans.With its advantages in non-invasiveness, miniaturization, and versatility, our acoustic tweezers will become a powerful tool for many disciplines of science and engineering.  

 

Acoustic tweezers based multichannel cells sorting

Acoustic Tweezers For Multichannel Sorting

 Xiaoyun Ding, et al., Standing Surface Acoustic Wave (SSAW) Based Multichannel Cell Sorting, Lab on a Chip, Vol.12, pp. 4228–4231, 2012. (was highlighted and reported by Kurzweil, NSF, Human Health & ScienceQuantum TimesFuturitySIP TRUNKINGDeviceSpaceEurekAlertUPIe-Science NewsLabSpacesHealth Canal,TG DailyGizmagPhysOrg, Product Design and DevelopmentScience DailyLaboratory EquipmentAzonano, The Engineer, R&D, )

Cell sorting is essential for many fundamental cell studies, cancer research, clinical medicine, and transplantation immunology. We developed an acoustic-based method that can precisely sort cell into five separate outlets of cells (Figure to the right), rendering it particularly desirable for multi-type cell sorting. Our device requires small sample volumes (~100 μl), making it an ideal tool for research labs and point-of-care diagnostics. Furthermore, it can be conveniently integrated with a small power supply, a fluorescent detection module, and a high-speed electrical feedback module to function as a fully integrated, portable, inexpensive, multi-color, miniature fluorescence-activated cell sorting (μFACS) system.

 

Tunnable cells patterning

Cell Patterning Using IDTs

[Xiaoyun Ding, et al., Lab on a Chip, Vol. 12, pp. 2491-2497, 2012. (featured as back cover image) ]

The ordered arrangement of biological cells and microscale objects plays an important role in many biological and colloidal studies such as microarrays, regenerative medicine, and tissue engineering. We have developed an acoustic-based tunable patterning technique that can control the cell pattern with the tunability of up to 72% [2]. This acoustic-based tunable patterning technique has the advantages of wide tunability, non-invasiveness, and ease of integration to lab-on-a-chip systems, and shall be valuable in many biological and tissue endingeering studies such as investigation of cell-cell interactions. Due to its significance, this work was selected as cover image at the journal Lab on a Chip.

 

SAW driven light shutter using poly­mer-dispersed liquid crystals (PDLCs)

[Y. J. Liu, X. Ding, et al. Advanced Materials, Vol. 23, pp. 1656-1659, 2011. (featured as front cover image) ]

A surface acoustic wave (SAW)-driven light shutter is demonstrated using poly­mer-dispersed liquid crystals (PDLCs). Our experiments show that a PDLC film switches from a non-transparent state to a transparent state when subjected to a SAW. The working mechanism is analyzed theoretically and the acousto-optic properties of the PDLC film are characterized. This swit­ching behavior results from the acoustic streaming-induced realignment of liquid crystal (LC) molecules as well as SAW-induced thermal diffusion. Such a device shows an excellent performance in terms of imaging quality and optical contrast, which is important for display applications and smart windows.