Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of brain development, providing an exceptional tool for studying the complexities of biology. Among these, cortical organoids, comprising in part of neurons, have been instrumental in providing early insights into brain formation, function, and pathology. Functional characteristics of cortical organoids, such as cellular morphology and electrophysiology, provide physiological insight into cellular states and are crucial for understanding the roles of cell types within their specific niches. And while progress has been made studying engineered neuronal systems, decoding the functional properties of neuronal networks and their role in producing behaviors depends in part on recognizing neuronal cell types, their general locations within the brain, and how they connect.

X-radiation (X-ray) imaging is one of the most common imaging techniques in medicine. Presently, thin-film transistor flat panel detectors are the gold standard for X-ray detection; however, these detectors average across the absorbed X-ray spectrum and thus suffer from poor material decomposition and lesion differentiation. Modern efforts to address this focus on three methods of energy differentiation: dual-shot, photon counting, and dual-layer detectors. Dual-shot detection utilizes a single detector to image a patient with two shots of X-rays at low and high energies. While this has been shown to effectively differentiate between soft and hard tissues, (e.g., chest radiography) this results in a higher dose level to the patient and motion artifacts from slight movement between images. Photon counting detectors offer an alternative to multiple shots, providing high spatial resolution, low dose, and multiple energy binning with photon weighting. However, these detectors also require more complex circuit design for fast readout, have limited material options with great enough yield and detective quantum efficiency at low to mid energy ranges, and are limited in detective area. Dual-layer detectors that stack two detector layers to each process low and high energy X-rays remove motion artifacts by utilizing a single shot of polyenergetic X-rays. These most commonly employ two indirect detectors separated by a Cu filtering layer, which photon-starves the second higher energy detector. Unfortunately, this also requires a higher X-ray intensity, resulting in a higher dose level to the patient.

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter "organoid") have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Modern methods of interfacing with organoids involve any combination of encoding information, decoding information, or perturbing the underlying dynamics through various timescales of plasticity. Our knowledge of biological learning rules has not yet translated to reliable methods for consistently training neural tissue in goal-directed ways. In vivo training methods commonly exploit principles of reinforcement learning and Hebbian learning to modify biological networks. However, in vitro training has not seen comparable success, and often cannot utilize the underlying, multi-regional circuits enabling dopaminergic learning. Successfully harnessing in vitro learning methods and systems could uniquely reveal fundamental mesoscale processing and learning principles. This may have profound implications, from developing targeted stimulation protocols for therapeutic interventions to creating energy-efficient bio-electronic systems.

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter “organoid”) have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Despite their potential, organoid experiments present several challenges. Organoids require a rigorous, months-long developmental process, demanding substantial resources and meticulous care to yield valuable data on aspects of biology such as neural unit electrophysiology, cytoarchitecture, and transcriptional regulation. Traditionally the data has been difficult to collect on a more frequent and consistent basis, which limits the breadth and depth of modern organoid biology. Generating and measuring organoids depend on media manipulations, imaging, and electrophysiological measurements. Historically these are labor- and skill-intensive processes which can increase risks associated with known human error and contamination.

Hybridization capture approaches allow targeted high-throughput sequencing analysis at reduced costs compared to shotgun sequencing. Hybridization capture is particularly useful in analyses of genomic data from ancient, environmental, and forensic samples, where target content is low, DNA is fragmented and multiplex PCR or other targeted approaches often fail. Hybridization capture involves the use of "bait" nucleotides that capture genomic sequences that are of particular interest for the researcher. Current bait synthesis methods require large-scale oligonucleotide chemical synthesis and/or in vitro transcription. Both RNA and DNA bait generation requires synthesizing template oligonucleotides using phosphoramidite chemistry. Microarray-based synthesis generates oligonucleotides in femtomole scales with high chemical coupling error rates. Templates synthesized at small-scale require enzymatic amplification before use in hybridization capture.The solution proposed here involves a simple and highly efficient method to generate target probes using isothermal amplification. Target sequences are circularized and then amplified by rolling circle amplification. This method generates concatemers comprising thousands of copies of the target seqeuence. Restriction digestion of the amplified product then produces probes to use in target enrichment applications. 

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.