Chin, J. Y. | bioRxiv Science

bioRxiv2026

A network of syringe-injectable bioelectronics for closed-loop therapeutic rescue

An on-body network of sensors and drug delivery implants could transform treatments for rapid-onset morbidities that require bystander intervention. During opioid overdoses, for example, lone and incapacitated victims often cannot self-administer life-saving naloxone in the minutes before respiratory collapse. However, the bulkiness of existing closed-loop systems threatens patient acceptance. Here, we present the Rapid Emergency Subcutaneous platform (RES-Q), a network of wearable sensors and syringe-implantable autoinjectors for closed-loop therapy. RES-Q implants are similar in size to FDA-approved drug rod implants and fit inside 6-gauge needles to facilitate outpatient administration. Informed by implant fibrosis fracture mechanics, RES-Q employs miniature jet injectors that deliver 0.4 mg human-relevant doses of naloxone through fibrotic encapsulation for rapid uptake. RES-Q implants communicate with wearable sensors through tissue conductivity, resulting in 25 nA standby current draws that ensure long-term functionality. In swine, we sequentially trigger multiple implants using ionic tissue communication. In rats, RES-Q detects fentanyl overdoses using wearable photoplethysmography sensors and performs autonomous, dose-titratable rescue in < 6 minutes.

bioengineering↗

bioRxiv2026

Lateral hypothalamic melanin-concentrating hormone neuron dynamics in rats during sensory stimulation and sugar sweetened alcoholic cocktail drinking

There is a dearth of information on how different cocktails sweetened with different sugars impact brain activity. Glucose enters the brain faster and in greater concentration than fructose and directly affects neuronal activity of melanin-concentrating hormone (MCH) neurons. MCH signaling promotes both glucose drinking and alcohol intake by integrating central and sensory inputs, but it is currently unknown how MCH neuronal activity relates to sweetened cocktail drinking. This study sought to investigate the relationship between MCH activity and sugar-sweetened alcoholic cocktail drinking. We also sought to compare MCH neuronal responses to the sugar solutions without alcohol as well as their response to sensory stimuli. In female and male rats, we used fiber photometry to monitor MCH neurons in response to sensory stimuli and during drinking of 10% glucose, 10% fructose, and glucose or fructose cocktails with 1.25% or 10% alcohol. We found that MCH activity rises in response to a variety of sensory stimuli and peaks before the start of drinking for all cocktails, before returning to baseline near the start of drinking. The cocktail type impacted the dynamics of MCH activity, where increased alcohol concentration resulted in earlier MCH activity for fructose but not glucose cocktails. Finally, we found that peak MCH activity during drinking is correlated with approach behavior for all sugar and cocktail types. These findings suggest that glucose and alcohol may interact to directly influence MCH activity. Further, MCH neurons may regulate cocktail drinking in response to sugar type and alcohol concentration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/719280v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@54685org.highwire.dtl.DTLVardef@59003eorg.highwire.dtl.DTLVardef@11f0358org.highwire.dtl.DTLVardef@114b524_HPS_FORMAT_FIGEXP M_FIG C_FIG New and noteworthyFiber photometry was used to monitor lateral hypothalamic melanin-concentrating hormone (MCH) neurons in male and female rats during sensory stimuli and drinking of glucose, fructose, or glucose- or fructose-sweetened alcoholic cocktails. Subsecond-scale changes in MCH activity occurred after stimuli. Peak MCH activity during drinking was correlated with approach behavior. Alcohol concentration only impacted MCH activity with fructose cocktails. We discuss the implications of MCH dynamics towards brain function, associative learning, and alcohol use disorder.

neuroscience↗

bioRxiv2026

Self-severing circuits facilitate passage of ingestible electronic sensor-guided therapeutics

Ingestible electronics enable the tracking and treatment of gastrointestinal and systemic diseases. However, bulky batteries and circuit boards require large capsules that can result in bowel obstruction, a medical emergency. Here, we engineered a 9 x 26 mm electronic pill capable of triggered severing into tiny pieces with sizes clinically proven to reduce obstruction risk. Our capsule enables multicomponent circuit boards to connect with separately encapsulated powering elements via conductive, interlocking connections. Heat induced softening of polyethylene glycol/polycaprolactone channels activates a spring to separate encapsulated components into inert 9 x 15 mm segments, facilitating intestinal passage. Separation triggers included closed-loop sensors and time-delay circuits. In vivo swine studies demonstrate the ability of our capsules to sense luminal oxygen changes via an optoelectronic sensor, locally trigger upadacitinib delivery, and facilitate safe excretion.

bioengineering↗