Touchable cell biophysics property recognition platforms enable multifunctional blood smart health care.

As a crucial biophysical property, red blood cell (RBC) deformability is pathologically altered in numerous disease states, and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs. However, there is still a gap in applying it further to point-of-care blood devices due to the large external equipment (high-resolution microscope and microfluidic pump), associated operational difficulties, and professional analysis. Herein, we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically. Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device. The biophysical properties of the cell population are obtained by the designed smartphone algorithm. Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing. We currently achieve 100% diagnostic accuracy for five typical clinical blood diseases (90 megaloblastic anemia, 78 myelofibrosis, 84 iron deficiency anemia, 48 thrombotic thrombocytopenic purpura, and 48 thalassemias) via real-world prospective implementation; furthermore, personalized blood quality (for transfusion in cardiac surgery) monitoring is achieved with an accuracy of 96.9%. This work suggests a potential basis for next-generation blood smart health care devices.

On-chip rapid drug screening of leukemia cells by acoustic streaming.

Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.

On-chip hydrogel arrays individually encapsulating acoustic formed multicellular aggregates for high throughput drug testing.

Multicellular aggregates in three-dimensional (3D) environments provide novel solid tumor models that can provide insight into in vivo drug resistance. Such models are therefore essential for developing new drugs and preventing the failure of clinical treatments. However, high-throughput cell cluster assembly and fabricating individual 3D environments that mimic the extracellular matrix (ECM) remain significant challenges. To rapidly produce mini 3D multicellular aggregate units, acoustic force assembly combined with ECM mimic hydrogel array encapsulation is developed and then integrated into a diffusion-based microfluidic device for high-throughput drug testing. The active acoustic force gathers human mononuclear leukemia cells (THP-1) into hundreds of multicellular clusters with a controllable size. Instead of continuous bulk materials, photosensitive gelatin methacryloyl (GelMA) hydrogel pillar arrays containing cell clusters at drug concentration gradients are obtained through selective area exposure. Ten azelaic acid (AZA) concentration gradient series are applied to 100 units to simultaneously test the multicellular cluster drug resistance to multiple drug conditions. Real-time green fluorescent protein (GFP) fluorescence is analyzed to monitor cell viability. The results show that cell aggregate activity is inversely related to the drug concentration in the hydrogel pillars, and shows lower sensitivity to drug toxicity than the activity of monolayer cultured cells. The 3D multicellular arrays provide numerous in vitro tumor models and can be directly used for downstream drug testing. This technology inherits the advantages of acoustic assembly, while being more flexible, practical, and high-throughput, and shows significant potential for use in further tumor related research and clinical practice.