BMSEED (www.bmseed.com) recently filed a non-provisional patent application (US Application No. 17/941,072) to extend the use of our 2D stretchable microelectrode array (sMEA) to the third dimension. The 3D-sMEA enables electrophysiological measurements from brain organoids and 3D tissue cultures (focus: Alzheimer’s Disease), with or without microfluidic channels. The technology underlying the filed IP creates MEAs with adjustable 3D pockets with embedded electrodes that physically wrap around the organoid (see figure), which will enable researchers to record neural signals from most of the surface (estimated 80%) of physiologically intact (not remodeled) organoids.

 More than 9 out of 10 clinical trials for new drugs that look promising in pre-clinical trials eventually fail. A major reason for many of these failures is that pre-clinical research mostly relies on 2D in vitro cell cultures and non-human animals, which often do not accurately replicate their 3D human counterparts, limiting the value of these pre-clinical models to predict clinical outcomes. Human induced pluripotent stem cell (hiPSC) derived 3D organoids address this weakness by replicating critical organ and tissue-specific features not observed in animal models or 2D cell cultures.

A major limitation for brain organoid research is the lack of adequate instrumentation for measuring neural electrical signals in 3D to monitor spatial and temporal network organization. Patch-clamp provides high-resolution intracellular recordings, but generally only from a small number of electrodes, thus limiting determination of network organization. Voltage and Ca2+-sensitive dyes do not require electrodes, but the recordings are limited by the bleaching of the dye, the smaller signal intensity, and the potential toxicity of the dye to the cells. MEAs record extracellular electrophysiological activity from numerous locations simultaneously. However, commercial MEAs are flat whereas organoids are spherical, i.e., the surface area for recording of neural activity, thus the accuracy to determine network organization, is limited. Moreover, organoids spread out and remodel on flat MEAs, which eliminates some of their benefits for disease modeling. Even current so-called 3D MEAs, which are essentially 2D MEAs with 50-100 mm spikes, do not eliminate these shortcomings. Our patent-pending technology eliminates these weaknesses.

The filing of this non-provisional patent application was supported by a $50,000 award from the NIH Small Business Technical and Business Assistance (TABA) Consulting Services program. The law firm Birch, Stewart, Kolasch & Birch, LLP (BSKB) assisted BMSEED with the writing and filing of the application. BSKB (www.bskb.com) is an internationally-recognized and highly-respected intellectual property law firm committed to obtaining and enforcing IP rights.

We greatly appreciate the support of the NIH!

Sincerely,
Team BMSEED