自從1928年Alexander Fleming發現Penicillin具有抑制細菌的效果後，人類首度擁有一項武器可以對抗微生物。自此，醫學發展開始突飛猛進，而人類的平均壽命也得以大幅成長。然而不到一百年的時間，隨著抗生素的過度濫用與依賴，反而造成愈來愈多具抗藥性的超級細菌在人類社會悄悄地蔓延，嚴重威脅人類的健康。因此如何協助病患正確地用藥，成為當前刻不容緩的議題。根據衛生福利部所公布民國102年國人死因分析，敗血症居台灣女性第十大死因，而在美國敗血症也是10大疾病相關的死因之一。而敗血症的治療除了病原的鑑定外，另一關鍵則是抗生素敏感性試驗(簡稱藥敏試驗)。目前臨床藥敏試驗緩慢，常必須與病情賽跑；在報告出爐之前，醫生也僅能在遵守用藥法則下投予經驗療法的抗生素。但如此抗生素的運用也不免使得治療成為一場賭局，往往難以達到預期效果，終究在確認為陽性血瓶，繼之培養出single colony的這兩天後，仍須等待至少再一整天的例行藥敏結果，始得可以適當的投藥。
給予「正確」且「快速」的抗生素治療，遂成為挽救病人生命的唯一手段。根據臨床統計研究，投以有效抗生素的時間點與敗血性休克(septic shock)病人的存活率有關。若病人能在初期獲得有效的抗生素治療，存活率為83%；而若有效治療延遲至第6 hr，則存活率降至42%。研究中亦統計了2634名疑似敗血症 (suspected sepsis)病人的資料，結果發現若給予正確治療，死亡率可從43%降為33%。
然而現今的藥敏性測試方法(antibiotic susceptibility test, AST)並未能滿足臨床上對快速提供細菌抗藥性資訊的需求，抗生素藥敏檢測法主要分成傳統檢測法及自動化儀器兩個部分。傳統的最低抑菌濃度(minimal inhibitory concentration, MIC)檢測以紙碇擴散法(disc diffusion test)、E-test, 連續稀釋塗盤法(agar dilution test)或是培養液連續稀釋法(broth dilution test)為主，通常需要花費一至數天的時間；而自動化儀器則以BioMérieux VITEK 2及BD Phenix systems為主流，優點在於以濁度、氧化還原等為檢測原理，檢測結果與傳統方法最接近，然而其購置成本昂貴且亦需要8-24 hours後
據2013年台灣院內感染監視資訊系統分析報告，抗甲氧苯青黴素金黃色葡萄球菌(MRSA)、抗萬古黴素腸球菌(VRE)、抗碳青黴烯類鮑氏不動桿菌(CRAB) 及抗碳青黴烯類克雷白氏肺炎桿菌(CRKP)之抗藥性比例分別約72.6%、21.5%、63.0%及11.1%。在臨床細菌抗藥性橫流的今日，經驗療法只能是一場期望值極低的賭注。而開發新藥往往需龐大資金以及動輒十年以上的研發時間，若能快速檢測臨床菌株的抗藥性則可解燃眉之急。
西元1827年英國植物學羅伯特·布朗觀察懸浮於水中的花粉，發現顯微鏡下花粉迸裂出之微粒會呈現不規則且隨機的運動，因而稱之為布朗運動。目前針對粒子布朗運動的瞭解已經相當完整，然而藉由量測布朗運動而應用於生物醫學方面的研究卻相當的少。本研究的基礎是假定當細菌對抗生素敏感時，培養期間數量就會因而減少(破壞細胞壁造成細菌爆裂)或沒有明顯增加(抑制DNA或蛋白合成)，反之亦然。透過直觀的方法偵測帶有細菌之螢光粒子的布朗運動，便可將其變化描繪出來。將此技術應用於藥敏試驗，可加快檢測速度，建立標準程序與檢測上下限，並整合其他方法提升此方法在臨床上的應用價值。
實驗結果顯示，的確可以找到一個閾值來預測此抗生素能否治療此次感染，和3天後的傳統細菌藥敏結果比較，初步的正確率可達8~9成。

According to the 2013 survey of top ten leading causes of death reported by the Ministry of Health and Welfare, sepsis has become the 10th cause of women’s death in Taiwan. In the U.S., sepsis also ranks in the top ten leading causes of death. Except for the identification of pathogen (IP), the key for a successful treatment of sepsis is the antimicrobial susceptibility test (AST). Clinically, doctors are used to performing an empirical therapy before the AST comes clear. However, the blind uses of antibiotics usually enhance the drug resistance and, even worse, may counteract the effects of future antibiotic therapies. Lately, automated platforms designed for the AST and IP are commonly used in research hospitals. The outcomes are highly comparable to conventional methods. However, the turnaround times for the AST and IP require 3-4 hours and 8-24 hours, respectively, which remain insufficient to improve the patient mortality (>50%). The next generation sequence (NGS) technique requires plenty of time (>24 hours) to complete the whole genome sequencing of pathogen and continuously alignment of antibiotic resistance gene sequence. The high cost and large time consumption therefore impede the NGS prevalence in clinical uses until now. Multiplex PCR, although claimed to get outcomes in 2-3 hours without time-consuming culture, is intrinsically incapable of dealing with Gram negative bacteria and unknown antibiotic resistance genes (unknown mechanism).
To achieve rapid, simple and quantitative diagnostics for the AST, we develop a unique technique based on Brownian motion of functionalized particles combining with immunoassays. As bacteria bind to the particles, Brownian motion will decline due to the increase of equivalent particle diameter. Herein, the assessment of the AST depends on a direct relationship between the concentration of pathogens and drug dosage. When pathogens are susceptible to some drugs, the growth of bacteria will be halted or reverse, resulting in none or increased Brownian motion over time; otherwise the Brownian motion will decrease over time. In addition, with several types of antibody-conjugated fluorescent particles co-suspended in a medium, several bacteria can be monitored simultaneously. Upon the success of this method, the goals to rapid (<2 h), less wasteful (~0.25 μL sample), low-cost and high sensitive ASTs are highly expected.
The novelty of this technique is focused on subtly linking the high sensitivity of Brownian motion with the particle diameter change by immune reactions. The relationship can therefore achieve fast time (<2 h), high precision, and low limit of detection (LOD~100 cfu/mL). Considering Brownian motion is a natural phenomenon, this technique can therefore benefit by low energy consumption, high repeatability, and flexible integration with other devices. Furthermore, we also spotlight the following innovations: (1) AST assessments based on the Brownian motion of micro particles and immunoassays; (2) a low sample volume requirement (~0.25 μL) enabled by a miniaturized platform; and (3) rapid mixing (<1 s) enabled by the integration with a self-developed technique, termed rapid electro kinetic patterning (REP). Additionally, the development of the technique will substantially aid the treatments of infectious diseases, decrease the waste of medical resources, prevent the antibiotic abuses, ameliorate drug resistance, and boost the human health.
Specifically, after a microchip, dynamic ranges, fundamental settings, bead-based immunoassays and an integration with REP established, we will use S. aureus, P. aeruginosa and E. coli to assess the effects of AST. Meanwhile, system limitation, sensitivity and a general procedure of operation will also be investigated. Then collaborating with clinics, we will attempt to compare our results from clinical samples with the conventional methods. Overall, the technique is a simple and powerful tool for the AST. The success of this technique will eventually provide a valuable option for the clinical diagnoses.

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