A portable and cost-effective real-time cardiotoxicity biosensor was developed using a CMOS imaging module extracted from a commercially available webcam. The detection system consists of a CMOS imaging module, a white LED and a pinhole. Real-time image processing was conducted by comparing reference and live frame images. To evaluate the engineered system, the effects of two different drugs, isoprenaline and doxorubicin, on the beating rate and beat-to-beat variations of ESC-derived cardiomyocytes were measured. The detection system was used to conclude that the beat-to-beat variability increased under treatment with both isoprenaline and doxorubicin. However, the beating rates increased upon the addition of isoprenaline but decreased for cultures supplemented with doxorubicin. Moreover, the response time for both the beating rates and the beat-to-beat variability of ESC-derived cardiomyocytes under treatment of isoprenaline was shorter than doxorubicin, although the amount of isoprenaline used in the measurement was three orders of magnitude lower than that of doxorubicin. Given its ability to perform real-time cell monitoring in a simple and inexpensive manner, the proposed system may be useful for a range of cell-based biosensing applications.

We demonstrate a novel fabrication technology of the microneedle array applied to painless drug delivery and minimal invasive blood extraction. The fabrication technology consists of a vertical deep X-ray exposure and a successive inclined deep X-ray exposure with a deep X-ray mask whose pattern has a hollow triangular array. The vertical exposure makes triangular column array with a needle conduit. With the successive inclined exposure, the column array shapes into the microneedle array without deep X-ray mask alignment. Changing the inclined angle and the gap between the mask and PMMA (PolyMethylMetaAcrylic) substrate, different types of microneedle array are fabricated in 750-1000 lm shafts length, 15 o -20 o tapered tips angle, and 190-300 lm bases area. The masks are designed to 400-600 lm triangles length, 70-100 lm conduits diameter, 25-60EA/5 mm 2 arrays density, and various tip shapes such as triangular, rounded, or arrow-like features. In the medical application, the fabricated PMMA microneedle array fulfills the structural requirements such as three-dimensional sharp tapered tip, HAR (High-AspectRatio) shafts, small invasive surface area, and out-of-plane structure. In the skin test, the microneedle array penetrates back of the hand skin with minimum pain and without tip break and blood is drawn after puncturing the skin. Hot embossing process and mold fabrication process are also investigated with silicon and PDMS mold. The processed tetrahedral PMMA structures are fabricated into the microneedle array by the additional deep X-ray exposure. With these processes, the microneedle array can be utilized as the mold base for electroplating process.