{"id":190,"date":"2022-12-28T10:16:10","date_gmt":"2022-12-28T10:16:10","guid":{"rendered":"https:\/\/microfluidics.creative-biolabs.com\/blog\/?p=190"},"modified":"2023-10-09T07:24:59","modified_gmt":"2023-10-09T07:24:59","slug":"kidney-organ-chip-construction-technology","status":"publish","type":"post","link":"https:\/\/microfluidics.creative-biolabs.com\/blog\/kidney-organ-chip-construction-technology\/","title":{"rendered":"Kidney Organ Chip Construction Technology"},"content":{"rendered":"<p><span style=\"font-size: 15px;\">The kidney is an important excretory organ of the human body. It is responsible for removing metabolites and certain wastes and poisons from the body. At the same time, it retains water and other useful substances through the reabsorption function, such as protein, amino acid, glucose, and sodium ions, to regulate water and electrolyte balance and maintain acid-base balance. The kidney is also an endocrine organ that can secrete various hormones and biologically active substances such as renin, erythropoietin, and prostaglandins. Therefore, research on renal physiology and disease-related topics is very extensive.<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-size: 15px;\"><strong>Major kidney diseases<\/strong><\/span><\/p>\n<ul>\n<li><span style=\"font-size: 15px;\"><strong>Glomerulonephritis (GN)<\/strong><\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">It is an inflammatory disease that damages the glomeruli. One of the main features is hyperfiltration and renal impairment. GN primarily results in structural defects in podocytes, one of the cell types that ensure normal renal function.<\/span><\/p>\n<ul>\n<li><span style=\"font-size: 15px;\"><strong>Polycystic Kidney Disease (PKD)<\/strong><\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">It is a group of monogenic disorders that lead to the development of renal cysts. The cysts destroy the renal tubular epithelium, leading to fibrosis, renal structural disturbances, and ultimately renal failure. To date, the exact mechanism leading to cyst formation has not been fully elucidated.<\/span><\/p>\n<ul>\n<li><span style=\"font-size: 15px;\"><strong>Renal fibrosis<\/strong><\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">It is a direct consequence of the limited regenerative capacity of the kidney after injury. Fibrosis involves excessive accumulation of extracellular matrix (ECM), often resulting in loss of function as normal tissue is replaced by scar tissue.<\/span><\/p>\n<ul>\n<li><span style=\"font-size: 15px;\"><strong>Kidney stones<\/strong><\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">It is a common urinary problem affecting approximately 10% of men and 6% of women and is increasing in prevalence in many developed countries. The factors underlying kidney stone formation remain unclear. Therefore, delving deeper into this complex mechanism may pave the way for the development of new strategies to prevent the disease.<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-size: 15px;\"><strong>Kidney Disease Research Model<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">Nephrotoxicity is one of the main causes of drug failure and drug development failure. Only about 2% of drug development failures can be screened out in the preclinical stage, and more than 20% of new drugs have serious adverse reactions only after the clinical stage. The reason why preclinical studies cannot predict nephrotoxicity well is the limitations of current preclinical cell culture and animal models. Cell culture methods simply grow living cells on Petri dishes, which lack blood flow and have different conditions from cells in a real <em>in vivo<\/em> environment. Animal models though allow for studies to be performed in a complete physiological environment, tubular secretion information obtained from animal studies cannot always predict human responses due to species differences. In contrast, the organ-on-a-chip, which can truly simulate human organs, has become an excellent solution. It has minimal functional units, uses primary human cells, and can even simulate real human organs&#8217; 3D structure and flow conditions.<\/span><\/p>\n<p style=\"text-align: center;\"><img decoding=\"async\" loading=\"lazy\" class=\" wp-image-191 aligncenter\" src=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/1-4-300x156.jpg\" alt=\"\" width=\"485\" height=\"252\" srcset=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/1-4-300x156.jpg 300w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/1-4-1024x533.jpg 1024w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/1-4-768x399.jpg 768w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/1-4.jpg 1269w\" sizes=\"(max-width: 485px) 100vw, 485px\" \/><span style=\"font-size: 12px;\">Schematic diagram of a human kidney organ-on-a-chip<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-size: 15px;\"><strong>Kidney Organ Chip Construction Technology<\/strong><\/span><\/p>\n<ul>\n<li><span style=\"font-size: 15px;\"><strong>Fabrication of Microfluidic Chips<\/strong><\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">1. Mask design<\/span><\/p>\n<p><span style=\"font-size: 15px;\">Use software to design mask patterns, and then use film to make the designed patterns into masks.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">2. Template making<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(1) Cleaning the glass substrate<\/span><\/p>\n<p><span style=\"font-size: 15px;\">30% hydrogen peroxide, ammonia water, and deionized water were prepared in a ratio of 1:1:5 to make an alkaline washing solution, and a 75 mm x 75 mm optical glass was placed in the alkaline washing solution, and heated in a water bath at 75 \u00b0C. After taking it out, ultrasonically clean it for 5 minutes, replace it with deionized water and repeat the cleaning three times, and then take out the optical glass to air dry.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(2) Uniform glue<\/span><\/p>\n<p><span style=\"font-size: 15px;\">After the photoresist was ultrasonically removed at 50 \u00b0C for 1 h to remove air bubbles, it was left to stand at room temperature for 30 min, and then the photoresist was loaded into the center of the optical glass with a plastic dropper, and the glue was evened out with a homogenizer.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(3) Pre-bake<\/span><\/p>\n<p><span style=\"font-size: 15px;\">After uniform coating, the optical glass substrate was baked at 95 \u00b0C for 30 min, and after cooling down to room temperature, the hardness of the photoresist was detected and the thickness of the photoresist was measured.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(4) Exposure<\/span><\/p>\n<p><span style=\"font-size: 15px;\">Cover the photoresist side of the optical glass with a mask, and use a UV exposure machine to crosslink the photoresist. The required exposure energy is related to the exposure time and the thickness of the photoresist.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(5) Post-baking<\/span><\/p>\n<p><span style=\"font-size: 15px;\">Place the exposed optical glass substrate on a horizontal hot plate and bake at 95 \u00b0C. After the mask pattern is revealed, place the optical glass substrate at room temperature to cool down.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(6) Development<\/span><\/p>\n<p><span style=\"font-size: 15px;\">Put the cooled optical glass substrate in ethyl lactate to remove the uncrosslinked photoresist, and check the development degree of the template with isopropanol, if there is white precipitation, continue to wash the template in ethyl lactate, and repeat the process until no white precipitate appears after placing the template in isopropanol.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">(7) Hard film<\/span><\/p>\n<p><span style=\"font-size: 15px;\">After drying the isopropanol on the surface of the template, check the details of the template with a microscope, then place it in an oven at 120 \u00b0C for 2 h to harden the film, cool down slowly, and cool the template to room temperature.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">3. PDMS chip processing<\/span><\/p>\n<p><span style=\"font-size: 15px;\">The PDMS prepolymer and PDMS curing agent were mixed at room temperature for 30 min at a volume ratio of 10:1, and then the mixed PDMS colloid was poured on the template, and the air bubbles in the PDMS colloid were removed by vacuum. Subsequently, the poured PDMS was placed in an oven and baked at 80 \u00b0C for 1 h to solidify. The cured PDMS is peeled off from the template, punched with a puncher, and then the PDMS chip is sealed according to the design requirements using a plasma cleaner.<\/span><\/p>\n<p><span style=\"font-size: 15px;\"><strong>\u00a0<\/strong><\/span><\/p>\n<ul>\n<li><span style=\"font-size: 15px;\"><strong>Kidney tubule chip assembly<\/strong><\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\"><strong>Monolayer renal tubular epithelial cell chip assembly<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">According to the needs of the experiment, the porous membrane planted with renal tubular epithelial cells was sandwiched between the blood pole piece and the urine pole piece, and fixed with screws and nuts. &#8220;Artificial urine&#8221; flows on the side of renal tubular epithelial cells, and &#8220;artificial blood&#8221; flows on the other side, and the two fluids exchange substances at the porous membrane with cells.<\/span><\/p>\n<p><span style=\"font-size: 15px;\"><strong>Kidney tubule peritubular chip assembly<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">The porous membrane planted with renal tubular perivascular endothelial cells and renal tubular epithelial cells is sandwiched between the blood pole block and the urine pole block in a back-to-back manner, and fixed with screws and nuts. Artificial urine flows at a flow rate of 1 L\/min on the side of renal tubular epithelial cells, and artificial blood flows at a flow rate of 1 L\/min on the side of renal tubular vascular endothelial cells. The two flows occur at the porous membrane with cell material exchange.<\/span><\/p>\n<p><span style=\"font-size: 15px;\"><strong>Application of Kidney Organ Chip Model<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\"><strong>Drug evaluation<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">About 20% of episodes of acquired renal failure are drug-induced. The kidney-on-a-chip model can reflect the dynamic changes of drugs in the body and the real response of human organs to drugs, and better make up for the shortcomings of existing <em>in vitro <\/em>models or animal experiments that deviate from the human body.<\/span><\/p>\n<p><span style=\"font-size: 15px;\"><strong>Disease research<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">Kidney-on-a-chip offers new opportunities to study kidney physiology and kidney disease as well as nephrotoxicity. For example, the main pathological changes of glomerular damage in the early stage of diabetic nephropathy can be reflected by constructing a kidney chip model containing primary glomerular tissue, matrix components, and vascular-like mechanical fluid.<\/span><\/p>\n<p><span style=\"font-size: 15px;\"><strong>Toxicological evaluation<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">Due to the complexity of the human body, the existing animal experiments and <em>in vitro <\/em>evaluation models cannot accurately reflect the human body&#8217;s response to various adverse factors. The kidney-on-a-chip model can better simulate the real response of the human body to pharmaceutical compounds and toxins, and significantly reduce the cost and time of toxicity assessment, so it is a very promising alternative strategy for animal experiments and <em>in vitro<\/em> evaluation models.<\/span><\/p>\n<p style=\"text-align: center;\">\u00a0<img decoding=\"async\" loading=\"lazy\" class=\" wp-image-192 aligncenter\" src=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/2-4-300x290.jpg\" alt=\"\" width=\"379\" height=\"366\" srcset=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/2-4-300x290.jpg 300w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/2-4-768x741.jpg 768w, https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-content\/uploads\/2023\/10\/2-4.jpg 811w\" sizes=\"(max-width: 379px) 100vw, 379px\" \/><span style=\"font-size: 12px;\">Kidney-on-a-Chip Applications<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-size: 15px;\"><strong>Reference<\/strong><strong>\uff1a<\/strong><\/span><\/p>\n<p><span style=\"font-size: 12px;\">[1] H Laverty, <em>et al<\/em>. How can we improve our understanding of cardiovascular safety liabilities to develop safer medicines?[J]. <em>Br J Pharmacol<\/em>, 2011, 163(4): 675-693.<\/span><\/p>\n<p><span style=\"font-size: 12px;\">[2] Scales C D, <em>et al<\/em>. Prevalence of Kidney Stones in the United States[J].\u00a0<em> Urol,<\/em>2012,\u00a062: 160\u2013165.\u00a0<\/span><\/p>\n<p><span style=\"font-size: 12px;\">[3] Paoli R, Samitier J. Mimicking the Kidney: A Key Role in Organ-on-Chip Development[J]. <em>Micromachines<\/em>. 2016, 7(7): 126.<\/span><\/p>\n<p><span style=\"font-size: 12px;\">[4] Naughton C A. Drug-induced nephrotoxicity[J]. <em>Am Fam Physician,<\/em>2008,\u00a078: 743\u2013750.<\/span><\/p>\n<p><span style=\"font-size: 12px;\">[5] Kim S, Takayama S. Organ-on-a-chip and the kidney[J]. <em>Kidney\u00a0Res Clin Pract<\/em>, 2015, 34(3): 165-169.<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-size: 15px;\"><strong>Related Services:<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\"><a href=\"https:\/\/microfluidics.creative-biolabs.com\/microfluidic-chip-development-for-organ-on-a-chip.htm\">Microfluidic Chip Development Services for Organ-On-A-Chip<\/a><\/span><\/p>\n<p><span style=\"font-size: 15px;\"><a href=\"https:\/\/microfluidics.creative-biolabs.com\/cell-culture-and-organ-on-chip-model-development-services.htm\">Cell Culture and Organ-On-A-Chip Model Development Services<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The kidney is an important excretory organ of the human body. It is responsible for removing metabolites and certain wastes and poisons from the body. At the same time, it retains water<a class=\"moretag\" href=\"https:\/\/microfluidics.creative-biolabs.com\/blog\/kidney-organ-chip-construction-technology\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":191,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6],"tags":[],"_links":{"self":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/190"}],"collection":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/comments?post=190"}],"version-history":[{"count":1,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/190\/revisions"}],"predecessor-version":[{"id":193,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/190\/revisions\/193"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media\/191"}],"wp:attachment":[{"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media?parent=190"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/categories?post=190"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microfluidics.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/tags?post=190"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}