## 1 Introduction  
The blood-brain barrier (BBB) is necessary for normal brain function and maintains the central nervous system (CNS) homeostatic environment. Specialized endothelial cells and supporting cells such as neurons, oligodendrocyte, microglia, astrocytes, and pericytes make up the blood-brain barrier (BBB) [1, 2]. Adherens junctions and tight junctions, along with a few other unique transport mechanisms, allow the blood-brain barrier (BBB) to regulate the entry of substances into the brain [3, 4]. The BBB's barrier qualities, however, also make it more difficult to treat CNS illnesses, since they prevent many large- and small-molecule medications from getting into the brain in amounts sufficient to cause a therapeutic reaction [5]. With respect to Alzheimer's disease (AD), studies show that A\(\beta_{1-42}\) plays a central role in A\(\beta\) accumulation and plaque formation in the brain [6, 7]. The blood-brain barrier (BBB) plays a crucial role in the regulation of A\(\beta\) levels in the brain, and its dysfunction is closely related to the accumulation of A\(\beta\) caused by Alzheimer's disease (AD) [6, 7]. Understanding vascular contributions to cognitive impairment and dementia (VCID) is significant due to the cognitive decline resulting from damage to the brain function [8]. Another aspect of AD-related emerging issues is cerebral amyloid angiopathy (CAA). CAA is a type of cerebrovascular disorder characterized by the accumulation of A\(\beta\)within the leptomeninges and small-to-medium-sized cerebral blood vessels [9]. CAA is associated with cognitive dysfunction, intracerebral hemorrhage (ICH), and microinfarcts. CAA is tightly linked with FDA-approved anti-A\(\beta\) immunotherapy as a side effect [10]. The main receptors for A\(\beta\) transport across the BBB from brain to blood and blood to brain are low-density lipoprotein receptor-related protein-1 (LRP1) and receptor for advanced glycation end products (RAGE), respectively [11; 12]. Tight junction (TJ) proteins such as ZO-1, claudi-5, and occludin are part of the components of the BBB and are considered, in part, important indicators of the morphological changes in the BBB [13]. Apart from the molecular basis of AD, this model can be used to model other neurological disorders and neurodegenerative diseases [14].  
Although whole-organism drug distribution can be studied using in vivo models, their use for BBB-penetrant antibody screening is limited due to the intricacy of this process and the reduced throughput of these investigations. Because of this, the field's in vivo research is supplemented with quicker and easier in vitro models, such as the transwell technique [15; 16; 17] and several on-a-chip technologies [18; 19; 20]. Even though in vitro BBB modeling has advanced significantly in recent years, a model that combines physiologically appropriate circumstances such as flow, coculture, and the absence of artificial membranes with quick, high-throughput readouts is still required. To address some of the key limitations of the current models, we generated a 3D bioengineered microfluidic membrane-free BBB against ECM using a phase guide method, a geometric feature that acts as a pressure barrier due to meniscus pinning. Here, we studied A\(\beta\) trafficking through the BBB using the two-lane perfusion-based microfluidic device. This perfusion-based microfluidic device would offer numerous advantages, including reproducibility, reduced sample volumes and cost, precise control of media flow and reagent delivery, and the ability to regulate the spatiotemporal parameters of the brain microenvironment.